WorldWideScience

Sample records for association study analyses

  1. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

    Science.gov (United States)

    Khankari, Nikhil K.; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei

    2016-01-01

    Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the

  2. Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer : Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

    NARCIS (Netherlands)

    Khankari, Nikhil K.; Shu, Xiao Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Eeles, Rosalind A.; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei; Blalock, Kendra; Campbell, Peter T.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Figueiredo, Jane; James Gauderman, W.; Gong, Jian; Green, Roger C.; Harju, John F.; Harrison, Tabitha A.; Jacobs, Eric J.; Jenkins, Mark A.; Jiao, Shuo; Li, Li; Lin, Yi; Manion, Frank J.; Moreno, Victor; Mukherjee, Bhramar; Raskin, Leon; Schumacher, Fredrick R.; Seminara, Daniela; Severi, Gianluca; Stenzel, Stephanie L.; Thomas, Duncan C.; Hopper, John L.; Southey, Melissa C.; Makalic, Enes; Schmidt, Daniel F.; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos Santos Silva, Isabel; Ahsan, Habib; Whittemore, Alice; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B.; Uitterlinden, Andre G.; Hofman, Albert; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Crisponi, Laura; Hall, Per; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Easton, Douglas F.; Turnbull, Clare; Rahman, Nazneen; Eeles, Rosalind; Kote-Jarai, Zsofia; Muir, Kenneth; Giles, Graham; Neal, David; Donovan, Jenny L.; Hamdy, Freddie C.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher; Schumacher, Fred; Travis, Ruth; Riboli, Elio; Hunter, David; Gapstur, Susan; Berndt, Sonja; Chanock, Stephen; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; McKay, James D.; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil; Teresa Landi, Maria; Heinrich, Joachim; Wu, Xifeng; Ye, Yuanqing; Christiani, David C.

    2016-01-01

    Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using

  3. Quality control and conduct of genome-wide association meta-analyses

    DEFF Research Database (Denmark)

    Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C

    2014-01-01

    Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC...

  4. Candidate gene association analyses for ketosis resistance in Holsteins.

    Science.gov (United States)

    Kroezen, V; Schenkel, F S; Miglior, F; Baes, C F; Squires, E J

    2018-06-01

    High-yielding dairy cattle are susceptible to ketosis, a metabolic disease that negatively affects the health, fertility, and milk production of the cow. Interest in breeding for more robust dairy cattle with improved resistance to disease is global; however, genetic evaluations for ketosis would benefit from the additional information provided by genetic markers. Candidate genes that are proposed to have a biological role in the pathogenesis of ketosis were investigated in silico and a custom panel of 998 putative single nucleotide polymorphism (SNP) markers was developed. The objective of this study was to test the associations of these new markers with deregressed estimated breeding values (EBV) for ketosis. A sample of 653 Canadian Holstein cows that had been previously genotyped with a medium-density SNP chip were regenotyped with the custom panel. The EBV for ketosis in first and later lactations were obtained for each animal and deregressed for use as pseudo-phenotypes for association analyses. Results of the mixed inheritance model for single SNP association analyses suggested 15 markers in 6 unique candidate genes were associated with the studied trait. Genes encoding proteins involved in metabolic processes, including the synthesis and degradation of fatty acids and ketone bodies, gluconeogenesis, lipid mobilization, and the citric acid cycle, were identified to contain SNP associated with ketosis resistance. This work confirmed the presence of previously described quantitative trait loci for dairy cattle, suggested novel markers for ketosis-resistance, and provided insight into the underlying biology of this disease. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals

    DEFF Research Database (Denmark)

    Kraja, Aldi T.; Cook, James P.; Warren, Helen R.

    2017-01-01

    Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data...

  6. Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

    Directory of Open Access Journals (Sweden)

    Kshitij Srivastava

    Full Text Available MicroRNAs (miRNAs are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs. Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444 and cancer risk by using a two-sided meta-analytic approach.An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR and 95% confidence interval (95% CI were used to investigate the strength of the association.Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096-1.481, P = 0.002. Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.

  7. Gene Set Analyses of Genome-Wide Association Studies on 49 Quantitative Traits Measured in a Single Genetic Epidemiology Dataset

    Directory of Open Access Journals (Sweden)

    Jihye Kim

    2013-09-01

    Full Text Available Gene set analysis is a powerful tool for interpreting a genome-wide association study result and is gaining popularity these days. Comparison of the gene sets obtained for a variety of traits measured from a single genetic epidemiology dataset may give insights into the biological mechanisms underlying these traits. Based on the previously published single nucleotide polymorphism (SNP genotype data on 8,842 individuals enrolled in the Korea Association Resource project, we performed a series of systematic genome-wide association analyses for 49 quantitative traits of basic epidemiological, anthropometric, or blood chemistry parameters. Each analysis result was subjected to subsequent gene set analyses based on Gene Ontology (GO terms using gene set analysis software, GSA-SNP, identifying a set of GO terms significantly associated to each trait (pcorr < 0.05. Pairwise comparison of the traits in terms of the semantic similarity in their GO sets revealed surprising cases where phenotypically uncorrelated traits showed high similarity in terms of biological pathways. For example, the pH level was related to 7 other traits that showed low phenotypic correlations with it. A literature survey implies that these traits may be regulated partly by common pathways that involve neuronal or nerve systems.

  8. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

    Directory of Open Access Journals (Sweden)

    Wenbo Tang

    Full Text Available Genome-wide association studies (GWAS have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1 in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7. In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8 at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  9. Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.

    Science.gov (United States)

    Sun, Xiangqing; Elston, Robert; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia I; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh

    2016-07-01

    Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

  10. [The maintenance of automatic analysers and associated documentation].

    Science.gov (United States)

    Adjidé, V; Fournier, P; Vassault, A

    2010-12-01

    The maintenance of automatic analysers and associated documentation taking part in the requirements of the ISO 15189 Standard and the French regulation as well have to be defined in the laboratory policy. The management of the periodic maintenance and documentation shall be implemented and fulfilled. The organisation of corrective maintenance has to be managed to avoid interruption of the task of the laboratory. The different recommendations concern the identification of materials including automatic analysers, the environmental conditions to take into account, the documentation provided by the manufacturer and documents prepared by the laboratory including procedures for maintenance.

  11. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Liang He

    2016-10-01

    Full Text Available Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1 endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2 time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM, cancer, cardiovascular diseases (CVDs and neurodegenerative diseases (NDs, and (3 both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08, out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2 and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory

  12. A clinical observational study analysing the factors associated with hyperventilation during actual cardiopulmonary resuscitation in the emergency department.

    Science.gov (United States)

    Park, Sang O; Shin, Dong Hyuk; Baek, Kwang Je; Hong, Dae Young; Kim, Eun Jung; Kim, Sang Chul; Lee, Kyeong Ryong

    2013-03-01

    This is the first study to identify the factors associated with hyperventilation during actual cardiopulmonary resuscitation (CPR) in the emergency department (ED). All CPR events in the ED were recorded by video from April 2011 to December 2011. The following variables were analysed using review of the recorded CPR data: ventilation rate (VR) during each minute and its associated factors including provider factors (experience, advanced cardiovascular life support (ACLS) certification), clinical factors (auscultation to confirm successful intubation, suctioning, and comments by the team leader) and time factors (time or day of CPR). Fifty-five adult CPR cases including a total of 673 min sectors were analysed. The higher rates of hyperventilation (VR>10/min) were delivered by inexperienced (53.3% versus 14.2%) or uncertified ACLS provider (52.2% versus 10.8%), during night time (61.0 versus 34.5%) or weekend CPR (53.1% versus 35.6%) and when auscultation to confirm successful intubation was performed (93.5% versus 52.8%) than not (all p<0.0001). However, experienced (25.3% versus 29.7%; p=0.448) or certified ACLS provider (20.6% versus 31.3%; p<0.0001) could not deliver high rate of proper ventilation (VR 8-10/min). Comment by the team leader was most strongly associated with the proper ventilation (odds ratio 7.035, 95% confidence interval 4.512-10.967). Hyperventilation during CPR was associated with inexperienced or uncertified ACLS provider, auscultation to confirm intubation, and night time or weekend CPR. And to deliver proper ventilation, comments by the team leader should be given regardless of providers' expert level. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Deep Sequencing of Three Loci Implicated in Large-Scale Genome-Wide Association Study Smoking Meta-Analyses.

    Science.gov (United States)

    Clark, Shaunna L; McClay, Joseph L; Adkins, Daniel E; Aberg, Karolina A; Kumar, Gaurav; Nerella, Sri; Xie, Linying; Collins, Ann L; Crowley, James J; Quakenbush, Corey R; Hillard, Christopher E; Gao, Guimin; Shabalin, Andrey A; Peterson, Roseann E; Copeland, William E; Silberg, Judy L; Maes, Hermine; Sullivan, Patrick F; Costello, Elizabeth J; van den Oord, Edwin J

    2016-05-01

    Genome-wide association study meta-analyses have robustly implicated three loci that affect susceptibility for smoking: CHRNA5\\CHRNA3\\CHRNB4, CHRNB3\\CHRNA6 and EGLN2\\CYP2A6. Functional follow-up studies of these loci are needed to provide insight into biological mechanisms. However, these efforts have been hampered by a lack of knowledge about the specific causal variant(s) involved. In this study, we prioritized variants in terms of the likelihood they account for the reported associations. We employed targeted capture of the CHRNA5\\CHRNA3\\CHRNB4, CHRNB3\\CHRNA6, and EGLN2\\CYP2A6 loci and flanking regions followed by next-generation deep sequencing (mean coverage 78×) to capture genomic variation in 363 individuals. We performed single locus tests to determine if any single variant accounts for the association, and examined if sets of (rare) variants that overlapped with biologically meaningful annotations account for the associations. In total, we investigated 963 variants, of which 71.1% were rare (minor allele frequency < 0.01), 6.02% were insertion/deletions, and 51.7% were catalogued in dbSNP141. The single variant results showed that no variant fully accounts for the association in any region. In the variant set results, CHRNB4 accounts for most of the signal with significant sets consisting of directly damaging variants. CHRNA6 explains most of the signal in the CHRNB3\\CHRNA6 locus with significant sets indicating a regulatory role for CHRNA6. Significant sets in CYP2A6 involved directly damaging variants while the significant variant sets suggested a regulatory role for EGLN2. We found that multiple variants implicating multiple processes explain the signal. Some variants can be prioritized for functional follow-up. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  15. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  16. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Bruggeman, Richard; Nolen, Willem A.; Penninx, Brenda W.

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  17. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; de Haan, Lieuwe; Linszen, Don H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  18. Characterizing the Severe Turbulence Environments Associated With Commercial Aviation Accidents. Part 1; 44 Case Study Synoptic Observational Analyses

    Science.gov (United States)

    Kaplan, Michael L.; Huffman, Allan W.; Lux, Kevin M.; Charney, Joseph J.; Riordan, Allan J.; Lin, Yuh-Lang; Proctor, Fred H. (Technical Monitor)

    2002-01-01

    A 44 case study analysis of the large-scale atmospheric structure associated with development of accident-producing aircraft turbulence is described. Categorization is a function of the accident location, altitude, time of year, time of day, and the turbulence category, which classifies disturbances. National Centers for Environmental Prediction Reanalyses data sets and satellite imagery are employed to diagnose synoptic scale predictor fields associated with the large-scale environment preceding severe turbulence. These analyses indicate a predominance of severe accident-producing turbulence within the entrance region of a jet stream at the synoptic scale. Typically, a flow curvature region is just upstream within the jet entrance region, convection is within 100 km of the accident, vertical motion is upward, absolute vorticity is low, vertical wind shear is increasing, and horizontal cold advection is substantial. The most consistent predictor is upstream flow curvature and nearby convection is the second most frequent predictor.

  19. The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies.

    Science.gov (United States)

    Beer, Tomasz M; Miller, Kurt; Tombal, Bertrand; Cella, David; Phung, De; Holmstrom, Stefan; Ivanescu, Cristina; Skaltsa, Konstantina; Naidoo, Shevani

    2017-12-01

    Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables. In baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78-0.84]) and 21% in PREVAIL (HR 0.79 [0.76-0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84-0.93]) and 10% (HR 0.90 [0.86-0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies. Several baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. A weighted U-statistic for genetic association analyses of sequencing data.

    Science.gov (United States)

    Wei, Changshuai; Li, Ming; He, Zihuai; Vsevolozhskaya, Olga; Schaid, Daniel J; Lu, Qing

    2014-12-01

    With advancements in next-generation sequencing technology, a massive amount of sequencing data is generated, which offers a great opportunity to comprehensively investigate the role of rare variants in the genetic etiology of complex diseases. Nevertheless, the high-dimensional sequencing data poses a great challenge for statistical analysis. The association analyses based on traditional statistical methods suffer substantial power loss because of the low frequency of genetic variants and the extremely high dimensionality of the data. We developed a Weighted U Sequencing test, referred to as WU-SEQ, for the high-dimensional association analysis of sequencing data. Based on a nonparametric U-statistic, WU-SEQ makes no assumption of the underlying disease model and phenotype distribution, and can be applied to a variety of phenotypes. Through simulation studies and an empirical study, we showed that WU-SEQ outperformed a commonly used sequence kernel association test (SKAT) method when the underlying assumptions were violated (e.g., the phenotype followed a heavy-tailed distribution). Even when the assumptions were satisfied, WU-SEQ still attained comparable performance to SKAT. Finally, we applied WU-SEQ to sequencing data from the Dallas Heart Study (DHS), and detected an association between ANGPTL 4 and very low density lipoprotein cholesterol. © 2014 WILEY PERIODICALS, INC.

  1. Genome-Wide Association Meta-Analyses to Identify Common Genetic Variants Associated with Hallux Valgus in Caucasian and African Americans

    Science.gov (United States)

    Hsu, Yi-Hsiang; Liu, Youfang; Hannan, Marian T.; Maixner, William; Smith, Shad B.; Diatchenko, Luda; Golightly, Yvonne M.; Menz, Hylton B.; Kraus, Virginia B.; Doherty, Michael; Wilson, A.G.; Jordan, Joanne M.

    2016-01-01

    Objective Hallux valgus (HV) affects ~36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with HV. Methods HV was assessed in 3 Caucasian cohorts (n=2,263, n=915, and n=1,231 participants, respectively). In each cohort, a GWAS was conducted using 2.5M imputed single nucleotide polymorphisms (SNPs). Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327). Results The proportion of HV variance explained by genome-wide genotyped SNPs was 50% in men and 48% in women. A higher proportion of genetic determinants of HV was sex-specific. The most significantly associated SNP in men was rs9675316 located on chr17q23-a24 near the AXIN2 gene (p=5.46×10−7); the most significantly associated SNP in women was rs7996797 located on chr13q14.1-q14.2 near the ESD gene (p=7.21×10−7). Genome-wide significant SNP-by-sex interaction was found for SNP rs1563374 located on chr11p15.1 near the MRGPRX3 gene (interaction p-value =4.1×10−9). The association signals diminished when combining men and women. Conclusion Findings suggest that the potential pathophysiological mechanisms of HV are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in osteoarthritis as well as new pathways, influencing skeletal development and inflammation. PMID:26337638

  2. Comparison of genome-wide association methods in analyses of admixed populations with complex familial relationships.

    Directory of Open Access Journals (Sweden)

    Naveen K Kadri

    Full Text Available Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P and family (K levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic markers. Linear models that ignored K were also tested. Correction for P was performed using principal component or structured association analysis. In analyses of simulated and real data, linear mixed models that corrected for K were able to control for type-I error, regardless of whether they also corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree and genomic relationships. In summary, in association studies using samples with both P and K, ancestries estimated using principal components or structured assignment were not sufficient to correct type-I errors. In such cases type-I errors may be controlled by use of linear mixed models with relationships derived from either pedigree or from genetic markers.

  3. Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrix™ and Narcolepsy.

    Directory of Open Access Journals (Sweden)

    Kaatje Bollaerts

    Full Text Available An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine Pandemrix™, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies.We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible.Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72-28.11 reduced to a median value of 6.06 (2.5th- 97.5th percentile: 2.49-15.1 and the French odds ratio of 5.43 (95% CI: 2.6-10.08 to 1.85 (2.5th-97.5th percentile: 0.85-4.08.We illustrate multiple-bias analyses using two studies on the Pandemrix™-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed Pandemrix™-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive.

  4. Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

    Science.gov (United States)

    Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar; Karmakar, Sougata; Mazumdar, Debasis

    2010-10-01

    Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

  5. Association Study between Lead and Zinc Accumulation at Different Physiological Systems of Cattle by Canonical Correlation and Canonical Correspondence Analyses

    International Nuclear Information System (INIS)

    Karmakar, Partha; Das, Pradip Kumar; Mondal, Seema Sarkar; Karmakar, Sougata; Mazumdar, Debasis

    2010-01-01

    Pb pollution from automobile exhausts around highways is a persistent problem in India. Pb intoxication in mammalian body is a complex phenomenon which is influence by agonistic and antagonistic interactions of several other heavy metals and micronutrients. An attempt has been made to study the association between Pb and Zn accumulation in different physiological systems of cattles (n = 200) by application of both canonical correlation and canonical correspondence analyses. Pb was estimated from plasma, liver, bone, muscle, kidney, blood and milk where as Zn was measured from all these systems except bone, blood and milk. Both statistical techniques demonstrated that there was a strong association among blood-Pb, liver-Zn, kidney-Zn and muscle-Zn. From observations, it can be assumed that Zn accumulation in cattles' muscle, liver and kidney directs Pb mobilization from those organs which in turn increases Pb pool in blood. It indicates antagonistic activity of Zn to the accumulation of Pb. Although there were some contradictions between the observations obtained from the two different statistical methods, the overall pattern of Pb accumulation in various organs as influenced by Zn were same. It is mainly due to the fact that canonical correlation is actually a special type of canonical correspondence analyses where linear relationship is followed between two groups of variables instead of Gaussian relationship.

  6. Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses.

    Science.gov (United States)

    Keogh, Ruth H; Mangtani, Punam; Rodrigues, Laura; Nguipdop Djomo, Patrick

    2016-01-05

    Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

  7. Variables associated with achievement in higher education: A systematic review of meta-analyses.

    Science.gov (United States)

    Schneider, Michael; Preckel, Franzis

    2017-06-01

    The last 2 decades witnessed a surge in empirical studies on the variables associated with achievement in higher education. A number of meta-analyses synthesized these findings. In our systematic literature review, we included 38 meta-analyses investigating 105 correlates of achievement, based on 3,330 effect sizes from almost 2 million students. We provide a list of the 105 variables, ordered by the effect size, and summary statistics for central research topics. The results highlight the close relation between social interaction in courses and achievement. Achievement is also strongly associated with the stimulation of meaningful learning by presenting information in a clear way, relating it to the students, and using conceptually demanding learning tasks. Instruction and communication technology has comparably weak effect sizes, which did not increase over time. Strong moderator effects are found for almost all instructional methods, indicating that how a method is implemented in detail strongly affects achievement. Teachers with high-achieving students invest time and effort in designing the microstructure of their courses, establish clear learning goals, and employ feedback practices. This emphasizes the importance of teacher training in higher education. Students with high achievement are characterized by high self-efficacy, high prior achievement and intelligence, conscientiousness, and the goal-directed use of learning strategies. Barring the paucity of controlled experiments and the lack of meta-analyses on recent educational innovations, the variables associated with achievement in higher education are generally well investigated and well understood. By using these findings, teachers, university administrators, and policymakers can increase the effectivity of higher education. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

    Directory of Open Access Journals (Sweden)

    Jingjing Liang

    2017-05-01

    Full Text Available Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8 for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4 and multiple-trait analyses identified one novel locus (FRMD3 for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

  9. Comparison of Genome-Wide Association Methods in Analyses of Admixed Populations with Complex Familial Relationships

    DEFF Research Database (Denmark)

    Kadri, Naveen; Guldbrandtsen, Bernt; Sørensen, Peter

    2014-01-01

    Population structure is known to cause false-positive detection in association studies. We compared the power, precision, and type-I error rates of various association models in analyses of a simulated dataset with structure at the population (admixture from two populations; P) and family (K......) levels. We also compared type-I error rates among models in analyses of publicly available human and dog datasets. The models corrected for none, one, or both structure levels. Correction for K was performed with linear mixed models incorporating familial relationships estimated from pedigrees or genetic...... corrected for P. In contrast, correction for P alone in linear models was insufficient. The power and precision of linear mixed models with and without correction for P were similar. Furthermore, power, precision, and type-I error rate were comparable in linear mixed models incorporating pedigree...

  10. Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses

    Directory of Open Access Journals (Sweden)

    Ruth H. Keogh

    2016-01-01

    Full Text Available Abstract Background Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Methods Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. Results The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Conclusions Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

  11. Meta-Analyses of the Associations of Respiratory Health Effectswith Dampness and Mold in Homes

    Energy Technology Data Exchange (ETDEWEB)

    Fisk, William J.; Lei-Gomez, Quanhong; Mendell, Mark J.

    2006-01-01

    The Institute of Medicine (IOM) of the National Academy of Sciences recently completed a critical review of the scientific literature pertaining to the association of indoor dampness and mold contamination with adverse health effects. In this paper, we report the results of quantitative meta-analysis of the studies reviewed in the IOM report. We developed point estimates and confidence intervals (CIs) to summarize the association of several respiratory and asthma-related health outcomes with the presence of dampness and mold in homes. The odds ratios and confidence intervals from the original studies were transformed to the log scale and random effect models were applied to the log odds ratios and their variance. Models were constructed both accounting for the correlation between multiple results within the studies analyzed and ignoring such potential correlation. Central estimates of ORs for the health outcomes ranged from 1.32 to 2.10, with most central estimates between 1.3 and 1.8. Confidence intervals (95%) excluded unity except in two of 28 instances, and in most cases the lower bound of the CI exceeded 1.2. In general, the two meta-analysis methods produced similar estimates for ORs and CIs. Based on the results of the meta-analyses, building dampness and mold are associated with approximately 30% to 80% increases in a variety of respiratory and asthma-related health outcomes. The results of these meta-analyses reinforce the IOM's recommendation that actions be taken to prevent and reduce building dampness problems.

  12. Genome-wide association studies and epistasis analyses of candidate genes related to age at menarche and age at natural menopause in a Korean population.

    Science.gov (United States)

    Pyun, Jung-A; Kim, Sunshin; Cho, Nam H; Koh, InSong; Lee, Jong-Young; Shin, Chol; Kwack, KyuBum

    2014-05-01

    The aim of this study was to identify polymorphisms and gene-gene interactions that are significantly associated with age at menarche and age at menopause in a Korean population. A total of 3,452 and 1,827 women participated in studies of age at menarche and age at natural menopause, respectively. Linear regression analyses adjusted for residence area were used to perform genome-wide association studies (GWAS), candidate gene association studies, and interactions between the candidate genes for age at menarche and age at natural menopause. In GWAS, four single nucleotide polymorphisms (SNPs; rs7528241, rs1324329, rs11597068, and rs6495785) were strongly associated with age at natural menopause (lowest P = 9.66 × 10). However, GWAS of age at menarche did not reveal any strong associations. In candidate gene association studies, SNPs with P menopause, there was a significant interaction between intronic SNPs on ADAM metallopeptidase with thrombospondin type I motif 9 (ADAMTS9) and SMAD family member 3 (SMAD3) genes (P = 9.52 × 10). For age at menarche, there were three significant interactions between three intronic SNPs on follicle-stimulating hormone receptor (FSHR) gene and one SNP located at the 3' flanking region of insulin-like growth factor 2 receptor (IGF2R) gene (lowest P = 1.95 × 10). Novel SNPs and synergistic interactions between candidate genes are significantly associated with age at menarche and age at natural menopause in a Korean population.

  13. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    Science.gov (United States)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  14. Environmental risk factors of pregnancy outcomes: a summary of recent meta-analyses of epidemiological studies.

    Science.gov (United States)

    Nieuwenhuijsen, Mark J; Dadvand, Payam; Grellier, James; Martinez, David; Vrijheid, Martine

    2013-01-15

    Various epidemiological studies have suggested associations between environmental exposures and pregnancy outcomes. Some studies have tempted to combine information from various epidemiological studies using meta-analysis. We aimed to describe the methodologies used in these recent meta-analyses of environmental exposures and pregnancy outcomes. Furthermore, we aimed to report their main findings. We conducted a bibliographic search with relevant search terms. We obtained and evaluated 16 recent meta-analyses. The number of studies included in each reported meta-analysis varied greatly, with the largest number of studies available for environmental tobacco smoke. Only a small number of the studies reported having followed meta-analysis guidelines or having used a quality rating system. Generally they tested for heterogeneity and publication bias. Publication bias did not occur frequently.The meta-analyses found statistically significant negative associations between environmental tobacco smoke and stillbirth, birth weight and any congenital anomalies; PM2.5 and preterm birth; outdoor air pollution and some congenital anomalies; indoor air pollution from solid fuel use and stillbirth and birth weight; polychlorinated biphenyls (PCB) exposure and birth weight; disinfection by-products in water and stillbirth, small for gestational age and some congenital anomalies; occupational exposure to pesticides and solvents and some congenital anomalies; and agent orange and some congenital anomalies. The number of meta-analyses of environmental exposures and pregnancy outcomes is small and they vary in methodology. They reported statistically significant associations between environmental exposures such as environmental tobacco smoke, air pollution and chemicals and pregnancy outcomes.

  15. Environmental risk factors of pregnancy outcomes: a summary of recent meta-analyses of epidemiological studies

    Directory of Open Access Journals (Sweden)

    Nieuwenhuijsen Mark J

    2013-01-01

    Full Text Available Abstract Background Various epidemiological studies have suggested associations between environmental exposures and pregnancy outcomes. Some studies have tempted to combine information from various epidemiological studies using meta-analysis. We aimed to describe the methodologies used in these recent meta-analyses of environmental exposures and pregnancy outcomes. Furthermore, we aimed to report their main findings. Methods We conducted a bibliographic search with relevant search terms. We obtained and evaluated 16 recent meta-analyses. Results The number of studies included in each reported meta-analysis varied greatly, with the largest number of studies available for environmental tobacco smoke. Only a small number of the studies reported having followed meta-analysis guidelines or having used a quality rating system. Generally they tested for heterogeneity and publication bias. Publication bias did not occur frequently. The meta-analyses found statistically significant negative associations between environmental tobacco smoke and stillbirth, birth weight and any congenital anomalies; PM2.5 and preterm birth; outdoor air pollution and some congenital anomalies; indoor air pollution from solid fuel use and stillbirth and birth weight; polychlorinated biphenyls (PCB exposure and birth weight; disinfection by-products in water and stillbirth, small for gestational age and some congenital anomalies; occupational exposure to pesticides and solvents and some congenital anomalies; and agent orange and some congenital anomalies. Conclusions The number of meta-analyses of environmental exposures and pregnancy outcomes is small and they vary in methodology. They reported statistically significant associations between environmental exposures such as environmental tobacco smoke, air pollution and chemicals and pregnancy outcomes.

  16. Brain areas associated with numbers and calculations in children: Meta-analyses of fMRI studies

    Directory of Open Access Journals (Sweden)

    Marie Arsalidou

    2018-04-01

    Full Text Available Children use numbers every day and typically receive formal mathematical training from an early age, as it is a main subject in school curricula. Despite an increase in children neuroimaging studies, a comprehensive neuropsychological model of mathematical functions in children is lacking. Using quantitative meta-analyses of functional magnetic resonance imaging (fMRI studies, we identify concordant brain areas across articles that adhere to a set of selection criteria (e.g., whole-brain analysis, coordinate reports and report brain activity to tasks that involve processing symbolic and non-symbolic numbers with and without formal mathematical operations, which we called respectively number tasks and calculation tasks. We present data on children 14 years and younger, who solved these tasks. Results show activity in parietal (e.g., inferior parietal lobule and precuneus and frontal (e.g., superior and medial frontal gyri cortices, core areas related to mental-arithmetic, as well as brain regions such as the insula and claustrum, which are not typically discussed as part of mathematical problem solving models. We propose a topographical atlas of mathematical processes in children, discuss findings within a developmental constructivist theoretical model, and suggest practical methodological considerations for future studies. Keywords: Mathematical cognition, Meta-analyses, fMRI, Children, Development, Insula

  17. Study and realization of a beam analyser of high intensity (10610)

    International Nuclear Information System (INIS)

    Perret-Gallix, D.

    1975-01-01

    A beam analyser working under high-beam intensity in the range of 10 6 to 10 10 particles per burst and giving position profile and intensity of this beam is studied. The reasons of this study, the principle of measurement, the construction of hardware and the different tests carried out on the chamber in order to evaluate the main features are related. The analyser is a multi-cellular ionisation chamber or stripe chamber; each cell made by a copper stripe (0.25mm wide) inserted between two high voltage planes (500V) forms a small independent ionisation chamber. This system, working under the on-line control of a mini-computer allows to associate to each event or event group the instantaneous position and profile of the beam [fr

  18. Studies of CTNNBL1 and FDFT1 variants and measures of obesity: analyses of quantitative traits and case-control studies in 18,014 Danes

    DEFF Research Database (Denmark)

    Andreasen, Camilla Helene; Mogensen, Mette Sloth; Borch-Johnsen, Knut

    2009-01-01

    of obesity-related quantitative traits, and case-control studies in large study samples of Danes. METHODS: The FDFT1 rs7001819, CTNNBL1 rs6013029 and rs6020846 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising 18,014 participants ascertained from; the population...... and a previous study. FDFT1 rs7001819 showed no association with obesity, neither when analysing quantitative traits nor when performing case-control studies of obesity.......). The most significantly associating variants within CTNNBL1 including rs6013029 and rs6020846 were additionally confirmed to associate with morbid obesity in a French Caucasian case-control sample. The aim of this study was to investigate the impact of these three variants on obesity, through analyses...

  19. Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses

    Science.gov (United States)

    Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Davies, Gail; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Miller, Michael B; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis O; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Thorleifsson, Gudmar; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Bergmann, Sven; Bjornsdottir, Gyda; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas J; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Liewald, David C; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Starr, John M; Stefansson, Kari; Steptoe, Andrew; Terracciano, Antonio; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    2016-01-01

    We conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings, and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are strongly enriched for association. PMID:27089181

  20. Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Krogh, Jesper; Nielsen, Marit Nyholm

    2017-01-01

    OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme......) was investigated. RESULTS: After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated...... with depression. One nominally significant interaction, most likely due to chance, was identified. CONCLUSION: The results indicate that ACE could be a potential candidate gene for depression....

  1. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

    DEFF Research Database (Denmark)

    Kar, Siddhartha P; Beesley, Jonathan; Amin Al Olama, Ali

    2016-01-01

    UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112...... (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell......-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. SIGNIFICANCE...

  2. Is bilingualism associated with a lower risk of dementia in community-living older adults? Cross-sectional and prospective analyses.

    Science.gov (United States)

    Yeung, Caleb M; St John, Philip D; Menec, Verena; Tyas, Suzanne L

    2014-01-01

    The aim of this study was to determine whether bilingualism is associated with dementia in cross-sectional or prospective analyses of older adults. In 1991, 1616 community-living older adults were assessed and were followed 5 years later. Measures included age, sex, education, subjective memory loss (SML), and the modified Mini-mental State Examination (3MS). Dementia was determined by clinical examination in those who scored below the cut point on the 3MS. Language status was categorized based upon self-report into 3 groups: English as a first language (monolingual English, bilingual English) and English as a Second Language (ESL). The ESL category had lower education, lower 3MS scores, more SML, and were more likely to be diagnosed with cognitive impairment, no dementia at both time 1 and time 2 compared with those speaking English as a first language. There was no association between being bilingual (ESL and bilingual English vs. monolingual) and having dementia at time 1 in bivariate or multivariate analyses. In those who were cognitively intact at time 1, there was no association between being bilingual and having dementia at time 2 in bivariate or multivariate analyses. We did not find any association between speaking >1 language and dementia.

  3. Association of study quality with completeness of reporting: have completeness of reporting and quality of systematic reviews and meta-analyses in major radiology journals changed since publication of the PRISMA statement?

    Science.gov (United States)

    Tunis, Adam S; McInnes, Matthew D F; Hanna, Ramez; Esmail, Kaisra

    2013-11-01

    To evaluate whether completeness of reporting of systematic reviews and meta-analyses in major radiology journals has changed since publication of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement; a secondary objective is to evaluate whether completeness of reporting (ie, PRISMA) is associated with study quality (ie, Assessing the Methodological Quality of Systematic Reviews [AMSTAR]). Systematic reviews and meta-analyses published in major radiology journals between January 2007 and December 2011 were identified by searching MEDLINE with the modified Montori method. Studies were reviewed independently by two investigators and assessed for adherence to the AMSTAR and PRISMA checklists. The average results were analyzed to assess for change in mean score before and after PRISMA publication and to assess results over time; a Pearson correlation coefficient was calculated to assess for any association between PRISMA and AMSTAR results. Included were 130 studies from 11 journals. Average PRISMA and AMSTAR results were 21.8 of 27 and 7.2 of 11, respectively. The average result was higher after publication of PRISMA, and PRISMA-reported items were 22.6 of 27 after publication of PRISMA versus 20.9 of 27 before publication of PRISMA; AMSTAR results were 7.7 of 11 after publication of PRISMA versus 6.7 of 11 before publication of PRISMA. There was a strong positive correlation (r = 0.86) between the PRISMA and AMSTAR results. There was high variability between journals. Radiology had the highest PRISMA reported items (24.7 of 27), and American Journal of Neuroradiology had the lowest (19.6 of 27). Two major areas for improvement include study protocol registration and assessment of risk of bias across studies (ie, publication bias). In major radiology journal studies, there was modest improvement in completeness of reporting of systematic reviews and meta-analyses, assessed by PRISMA, which was strongly associated with higher study

  4. SNPassoc: an R package to perform whole genome association studies.

    Science.gov (United States)

    González, Juan R; Armengol, Lluís; Solé, Xavier; Guinó, Elisabet; Mercader, Josep M; Estivill, Xavier; Moreno, Víctor

    2007-03-01

    The popularization of large-scale genotyping projects has led to the widespread adoption of genetic association studies as the tool of choice in the search for single nucleotide polymorphisms (SNPs) underlying susceptibility to complex diseases. Although the analysis of individual SNPs is a relatively trivial task, when the number is large and multiple genetic models need to be explored it becomes necessary a tool to automate the analyses. In order to address this issue, we developed SNPassoc, an R package to carry out most common analyses in whole genome association studies. These analyses include descriptive statistics and exploratory analysis of missing values, calculation of Hardy-Weinberg equilibrium, analysis of association based on generalized linear models (either for quantitative or binary traits), and analysis of multiple SNPs (haplotype and epistasis analysis). Package SNPassoc is available at CRAN from http://cran.r-project.org. A tutorial is available on Bioinformatics online and in http://davinci.crg.es/estivill_lab/snpassoc.

  5. Genome-Wide Association Study in Obsessive-Compulsive Disorder: Results from the OCGAS

    Science.gov (United States)

    Mattheisen, Manuel; Samuels, Jack F.; Wang, Ying; Greenberg, Benjamin D.; Fyer, Abby J.; McCracken, James T.; Geller, Daniel A.; Murphy, Dennis L.; Knowles, James A.; Grados, Marco A.; Riddle, Mark A.; Rasmussen, Steven A.; McLaughlin, Nicole C.; Nurmi, Erica; Askland, Kathleen D.; Qin, Hai-De; Cullen, Bernadette A.; Piacentini, John; Pauls, David L.; Bienvenu, O. Joseph; Stewart, S. Evelyn; Liang, Kung-Yee; Goes, Fernando S.; Maher, Brion; Pulver, Ann E.; Shugart, Yin-Yao; Valle, David; Lange, Cristoph; Nestadt, Gerald

    2014-01-01

    Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients, with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1 065 families (containing 1 406 patients with OCD), combined with population-based samples (resulting in a total sample of 5 061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at SNP- and gene-levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13×10−7). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of GWAS signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2, and PTPRD. Analyses at the gene-level revealed association of IQCK and C16orf88 (both P<1×10−6, experiment-wide significant), as well as OFCC1 (P=6.29×10−5). The suggestive findings in this study await replication in larger samples. PMID:24821223

  6. A weighted U statistic for association analyses considering genetic heterogeneity.

    Science.gov (United States)

    Wei, Changshuai; Elston, Robert C; Lu, Qing

    2016-07-20

    Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Identifying Virulence-Associated Genes Using Transcriptomic and Proteomic Association Analyses of the Plant Parasitic Nematode Bursaphelenchus mucronatus

    Directory of Open Access Journals (Sweden)

    Lifeng Zhou

    2016-09-01

    Full Text Available Bursaphelenchus mucronatus (B. mucronatus isolates that originate from different regions may vary in their virulence, but their virulence-associated genes and proteins are poorly understood. Thus, we conducted an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ to analyse transcriptomic and proteomic data of highly and weakly virulent B. mucronatus isolates during the pathogenic processes. Approximately 40,000 annotated unigenes and 5000 proteins were gained from the isolates. When we matched all of the proteins with their detected transcripts, a low correlation coefficient of r = 0.138 was found, indicating probable post-transcriptional gene regulation involved in the pathogenic processes. A functional analysis showed that five differentially expressed proteins which were all highly expressed in the highly virulent isolate were involved in the pathogenic processes of nematodes. Peroxiredoxin, fatty acid- and retinol-binding protein, and glutathione peroxidase relate to resistance against plant defence responses, while β-1,4-endoglucanase and expansin are associated with the breakdown of plant cell walls. Thus, the pathogenesis of B. mucronatus depends on its successful survival in host plants. Our work adds to the understanding of B. mucronatus’ pathogenesis, and will aid in controlling B. mucronatus and other pinewood nematode species complexes in the future.

  8. Contour plot assessment of existing meta-analyses confirms robust association of statin use and acute kidney injury risk.

    Science.gov (United States)

    Chevance, Aurélie; Schuster, Tibor; Steele, Russell; Ternès, Nils; Platt, Robert W

    2015-10-01

    Robustness of an existing meta-analysis can justify decisions on whether to conduct an additional study addressing the same research question. We illustrate the graphical assessment of the potential impact of an additional study on an existing meta-analysis using published data on statin use and the risk of acute kidney injury. A previously proposed graphical augmentation approach is used to assess the sensitivity of the current test and heterogeneity statistics extracted from existing meta-analysis data. In addition, we extended the graphical augmentation approach to assess potential changes in the pooled effect estimate after updating a current meta-analysis and applied the three graphical contour definitions to data from meta-analyses on statin use and acute kidney injury risk. In the considered example data, the pooled effect estimates and heterogeneity indices demonstrated to be considerably robust to the addition of a future study. Supportingly, for some previously inconclusive meta-analyses, a study update might yield statistically significant kidney injury risk increase associated with higher statin exposure. The illustrated contour approach should become a standard tool for the assessment of the robustness of meta-analyses. It can guide decisions on whether to conduct additional studies addressing a relevant research question. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Seismic risk analyses in the German Risk Study, phase B

    International Nuclear Information System (INIS)

    Hosser, D.; Liemersdorf, H.

    1991-01-01

    The paper discusses some aspects of the seismic risk part of the German Risk Study for Nuclear Power Plants, Phase B. First simplified analyses in Phase A of the study allowed only a rough classification of structures and systems of the PWR reference plant according to their seismic risk contribution. These studies were extended in Phase B using improved models for the dynamic analyses of buildings, structures and components as well as for the probabilistic analyses of seismic loading, failure probabilities and event trees. The methodology of deriving probabilistic seismic load descriptions is explained and compared with the methods in Phase A of the study and in other studies. Some details of the linear and nonlinear dynamic analyses of structures are reported in order to demonstrate the influence of different assumptions for material behaviour and failure criteria. The probabilistic structural and event tree analyses are discussed with respect to distribution assumptions, acceptable simplifications and model uncertainties. Some results for the PWR reference plant are given. (orig.)

  10. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    Science.gov (United States)

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. PMID:27432226

  11. Proteomic and phosphoproteomic analyses of chromatin-associated proteins from Arabidopsis thaliana

    KAUST Repository

    Bigeard, Jean

    2014-07-10

    The nucleus is the organelle where basically all DNA-related processes take place in eukaryotes, such as replication, transcription, and splicing as well as epigenetic regulation. The identification and description of the nuclear proteins is one of the requisites toward a comprehensive understanding of the biological functions accomplished in the nucleus. Many of the regulatory mechanisms of protein functions rely on their PTMs among which phosphorylation is probably one of the most important properties affecting enzymatic activity, interaction with other molecules, localization, or stability. So far, the nuclear and subnuclear proteome and phosphoproteome of the model plant Arabidopsis thaliana have been the subject of very few studies. In this work, we developed a purification protocol of Arabidopsis chromatin-associated proteins and performed proteomic and phosphoproteomic analyses identifying a total of 879 proteins of which 198 were phosphoproteins that were mainly involved in chromatin remodeling, transcriptional regulation, and RNA processing. From 230 precisely localized phosphorylation sites (phosphosites), 52 correspond to hitherto unidentified sites. This protocol and data thereby obtained should be a valuable resource for many domains of plant research.

  12. Proteomic and phosphoproteomic analyses of chromatin-associated proteins from Arabidopsis thaliana

    KAUST Repository

    Bigeard, Jean; Rayapuram, Naganand; Bonhomme, Ludovic; Hirt, Heribert; Pflieger, Delphine

    2014-01-01

    The nucleus is the organelle where basically all DNA-related processes take place in eukaryotes, such as replication, transcription, and splicing as well as epigenetic regulation. The identification and description of the nuclear proteins is one of the requisites toward a comprehensive understanding of the biological functions accomplished in the nucleus. Many of the regulatory mechanisms of protein functions rely on their PTMs among which phosphorylation is probably one of the most important properties affecting enzymatic activity, interaction with other molecules, localization, or stability. So far, the nuclear and subnuclear proteome and phosphoproteome of the model plant Arabidopsis thaliana have been the subject of very few studies. In this work, we developed a purification protocol of Arabidopsis chromatin-associated proteins and performed proteomic and phosphoproteomic analyses identifying a total of 879 proteins of which 198 were phosphoproteins that were mainly involved in chromatin remodeling, transcriptional regulation, and RNA processing. From 230 precisely localized phosphorylation sites (phosphosites), 52 correspond to hitherto unidentified sites. This protocol and data thereby obtained should be a valuable resource for many domains of plant research.

  13. Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

    Science.gov (United States)

    Xiao, Su-Mei; Kung, Annie Wai Chee; Gao, Yi; Lau, Kam-Shing; Ma, Alvin; Zhang, Zhen-Lin; Liu, Jian-Min; Xia, Wiebo; He, Jin-Wei; Zhao, Lin; Nie, Min; Fu, Wei-Zhen; Zhang, Min-Jia; Sun, Jing; Kwan, Johnny S H; Tso, Gloria Hoi Wan; Dai, Zhi-Jie; Cheung, Ching-Lung; Bow, Cora H; Leung, Anskar Yu Hung; Tan, Kathryn Choon Beng; Sham, Pak Chung

    2012-04-01

    Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.

  14. Study on drug costs associated with COPD prescription medicine in Denmark

    DEFF Research Database (Denmark)

    Jakobsen, M; Anker, N; Dollerup, J

    2013-01-01

    that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. OBJECTIVES: To analyse the societal costs associated with prescription medicine for COPD in Denmark. METHODS: The study was designed as a nationwide retrospective register study...... in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70,000-75,000 (EUR 9,416-10,089) per patient (2010 prices). CONCLUSION: The costs associated with prescription medicine for COPD in Denmark...... of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who...

  15. STUDY ON DRUG COSTS ASSOCIATED WITH COPD PRESCRIPTION MEDICINE IN DENMARK

    DEFF Research Database (Denmark)

    Jakobsen, Iris Marie; Anker, Niels; Dolleru, Jens

    2012-01-01

    that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. OBJECTIVES: To analyse the societal costs associated with prescription medicine for COPD in Denmark. METHODS: The study was designed as a nationwide retrospective register study...... in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70,000-75,000 (EUR 9,416-10,089) per patient (2010 prices). CONCLUSION: The costs associated with prescription medicine for COPD in Denmark...... of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who...

  16. permGPU: Using graphics processing units in RNA microarray association studies

    Directory of Open Access Journals (Sweden)

    George Stephen L

    2010-06-01

    Full Text Available Abstract Background Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed. Results We have developed a CUDA based implementation, permGPU, that employs graphics processing units in microarray association studies. We illustrate the performance and applicability of permGPU within the context of permutation resampling for a number of test statistics. An extensive simulation study demonstrates a dramatic increase in performance when using permGPU on an NVIDIA GTX 280 card compared to an optimized C/C++ solution running on a conventional Linux server. Conclusions permGPU is available as an open-source stand-alone application and as an extension package for the R statistical environment. It provides a dramatic increase in performance for permutation resampling analysis in the context of microarray association studies. The current version offers six test statistics for carrying out permutation resampling analyses for binary, quantitative and censored time-to-event traits.

  17. Genome-wide association analyses of expression phenotypes.

    Science.gov (United States)

    Chen, Gary K; Zheng, Tian; Witte, John S; Goode, Ellen L; Gao, Lei; Hu, Pingzhao; Suh, Young Ju; Suktitipat, Bhoom; Szymczak, Silke; Woo, Jung Hoon; Zhang, Wei

    2007-01-01

    A number of issues arise when analyzing the large amount of data from high-throughput genotype and expression microarray experiments, including design and interpretation of genome-wide association studies of expression phenotypes. These issues were considered by contributions submitted to Group 1 of the Genetic Analysis Workshop 15 (GAW15), which focused on the association of quantitative expression data. These contributions evaluated diverse hypotheses, including those relevant to cancer and obesity research, and used various analytic techniques, many of which were derived from information theory. Several observations from these reports stand out. First, one needs to consider the genetic model of the trait of interest and carefully select which single nucleotide polymorphisms and individuals are included early in the design stage of a study. Second, by targeting specific pathways when analyzing genome-wide data, one can generate more interpretable results than agnostic approaches. Finally, for datasets with small sample sizes but a large number of features like the Genetic Analysis Workshop 15 dataset, machine learning approaches may be more practical than traditional parametric approaches. (c) 2007 Wiley-Liss, Inc.

  18. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses

    Science.gov (United States)

    Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-01-01

    Objective To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. Data sources A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Study eligibility criteria Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Outcome measures Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. Results 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. Conclusions This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to

  19. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

    Directory of Open Access Journals (Sweden)

    Samuel E Jones

    2016-08-01

    Full Text Available Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8, including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12 and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10. The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8. For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16 and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9. Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05; undersleeping and BMI (rG = 0.147, P = 1x10-5 and oversleeping and BMI (rG = 0.097, P = 0.04, Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and

  20. Association of Helicobacter pylori infection with chronic atrophic gastritis: Meta-analyses according to type of disease definition.

    Science.gov (United States)

    Weck, Melanie N; Brenner, Hermann

    2008-08-15

    Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG). A large variety of definitions of CAG have been used in epidemiologic studies in the past. The aim of this work was to systematically review and summarize estimates of the association between H. pylori infection and CAG according to the various definitions of CAG. Articles on the association between H. pylori infection and CAG published until July 2007 were identified. Separate meta-analyses were carried out for studies defining CAG based on gastroscopy with biopsy, serum pepsinogen I (PG I) only, the pepsinogen I/pepsinogen II ratio (PG I/PG II ratio) only, or a combination of PG I and the PG I/PG II ratio. Numbers of identified studies and summary odds ratios (OR) (95% confidence intervals) were as follows: gastroscopy with biopsy: n = 34, OR = 6.4 (4.0-10.1); PG I only: n = 13, OR = 0.9 (0.7-1.2); PG I/PG II ratio: n = 8, OR = 7.2 (3.1-16.8); combination of PG I and the PG I/PG II ratio: n = 20, OR = 5.7 (4.4-7.5). Studies with CAG definitions based on gastroscopy with biopsy or the PG I/PG II ratio (alone or in combination with PG I) yield similarly strong associations of H. pylori with CAG. The association is missed entirely in studies where CAG is defined by PG I only. (c) 2008 Wiley-Liss, Inc.

  1. Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS).

    Science.gov (United States)

    Ammann, Eric M; Pottala, James V; Robinson, Jennifer G; Espeland, Mark A; Harris, William S

    2017-06-01

    To assess whether red blood cell (RBC) docosahexaenoic acid and eicosapentaenoic acid (DHA+EPA) levels have a protective association with the risk of dementia in older women. RBC DHA+EPA levels were assessed at baseline, and cognitive status was evaluated annually in a cohort of 6706 women aged ≥65 years who participated in the Women's Health Initiative Memory Study (WHIMS). Cox regression was used to quantify the association between RBC DHA+EPA and the risk of probable dementia, independent of major dementia risk factors. During a median follow-up period of 9.8 years, 587 incident cases of probable dementia were identified. After adjusting for demographic, clinical, and behavioral risk factors, a one standard deviation increase in DHA+EPA levels was associated with a significantly lower risk of dementia (HR = 0.92, 95% CI: 0.84, 1.00; p < 0.05). This effect estimate did not meaningfully change after further adjustment for baseline cognitive function and APOE genotype. For women with high DHA+EPA exposure (1SD above mean) compared to low exposure (1SD below mean), the adjusted 15-year absolute risk difference for dementia was 2.1% (95% CI: 0.2%, 4.0%). In secondary analyses, we also observed a protective association with longitudinal change in Modified Mini-Mental State (3MS) Exam scores, but no significant association with incident MCI, PD/MCI, or baseline 3MS scores. Higher levels of DHA+EPA may help protect against the development of dementia. Results from prospective randomized controlled trials of DHA+EPA supplementation are needed to help clarify whether this association is causal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    2011-02-01

    Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

  3. Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

    Science.gov (United States)

    Rueda, Sergio; Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

    2016-07-13

    To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living

  4. Summary of Electric Distribution System Analyses with a focus on DERs

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yingying [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Homer, Juliet S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McDermott, Thomas E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Coddington, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sigrin, Benjamin [National Renewable Energy Lab. (NREL), Golden, CO (United States); Mather, Barry [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-04-28

    The purpose of this document is to summarize types of electric distribution system analyses along with their application and relative maturity. Particular emphasis is placed on analyses associated with distributed energy resources (DERs). Analyses are separated into the categories of power flow, power quality, fault analysis, dynamic analysis and market analysis. Studies associated with DERs are called out in a separate section.

  5. Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

    OpenAIRE

    Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Smith, Jennifer A.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Yanek, Lisa R.; Schwander, Karen; Tajuddin, Salman M.; Sofer, Tamar; Kim, Wonji; Kayima, James

    2017-01-01

    © 2017 Public Library of Science. All Rights Reserved. Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genom...

  6. Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia.

    Science.gov (United States)

    Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

    2009-11-01

    Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.

  7. Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

    LENUS (Irish Health Repository)

    2010-05-01

    Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

  8. Financial relationships in economic analyses of targeted therapies in oncology.

    Science.gov (United States)

    Valachis, Antonis; Polyzos, Nikolaos P; Nearchou, Andreas; Lind, Pehr; Mauri, Davide

    2012-04-20

    A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.

  9. Associations between the Objectively Measured Office Environment and Workplace Step Count and Sitting Time: Cross-Sectional Analyses from the Active Buildings Study.

    Science.gov (United States)

    Fisher, Abi; Ucci, Marcella; Smith, Lee; Sawyer, Alexia; Spinney, Richard; Konstantatou, Marina; Marmot, Alexi

    2018-06-01

    Office-based workers spend a large proportion of the day sitting and tend to have low overall activity levels. Despite some evidence that features of the external physical environment are associated with physical activity, little is known about the influence of the spatial layout of the internal environment on movement, and the majority of data use self-report. This study investigated associations between objectively-measured sitting time and activity levels and the spatial layout of office floors in a sample of UK office-based workers. Participants wore activPAL accelerometers for at least three consecutive workdays. Primary outcomes were steps and proportion of sitting time per working hour. Primary exposures were office spatial layout, which was objectively-measured by deriving key spatial variables: 'distance from each workstation to key office destinations', 'distance from participant's workstation to all other workstations', 'visibility of co-workers', and workstation 'closeness'. 131 participants from 10 organisations were included. Fifty-four per cent were female, 81% were white, and the majority had a managerial or professional role (72%) in their organisation. The average proportion of the working hour spent sitting was 0.7 (SD 0.15); participants took on average 444 (SD 210) steps per working hour. Models adjusted for confounders revealed significant negative associations between step count and distance from each workstation to all other office destinations (e.g., B = -4.66, 95% CI: -8.12, -1.12, p office destinations (e.g., B = -6.45, 95% CI: -11.88, -0.41, p office destinations the less they walked, suggesting that changing the relative distance between workstations and other destinations on the same floor may not be the most fruitful target for promoting walking and reducing sitting in the workplace. However, reported effect sizes were very small and based on cross-sectional analyses. The approaches developed in this study could be applied to other

  10. Meta-analyses of HFE variants in coronary heart disease.

    Science.gov (United States)

    Lian, Jiangfang; Xu, Limin; Huang, Yi; Le, Yanping; Jiang, Danjie; Yang, Xi; Xu, Weifeng; Huang, Xiaoyan; Dong, Changzheng; Ye, Meng; Zhou, Jianqing; Duan, Shiwei

    2013-09-15

    HFE gene variants can cause hereditary hemochromatosis (HH) that often comes along with an increased risk of coronary heart disease (CHD). The goal of our study is to assess the contribution of four HFE gene variants to the risk of CHD. We conducted four meta-analyses of the studies examining the association between four HFE gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical. Meta-analyses showed that HFE rs1799945-G allele was associated with a 6% increased risk of CHD (P=0.02, odds ratio (OR)=1.06, 95% confidence interval (CI)=1.01-1.11). However, no association between the other three HFE gene variants (rs1800562, rs1800730, and rs9366637) and CHD risk was observed by the meta-analyses (all P values>0.05). In addition, the results of our case-control study indicated that rs1800562 and rs1800730 were monomorphic, and that rs1799945 and rs9366637 were not associated with CHD in Han Chinese. Our meta-analysis suggested that a significant association existed between rs1799945 mutation and CHD, although this mutation was rare in Han Chinese. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

    Science.gov (United States)

    Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

    2012-01-01

    Objective Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results. PMID:19839995

  12. Association Study of Three Gene Polymorphisms Recently Identified by a Genome-Wide Association Study with Obesity-Related Phenotypes in Chinese Children.

    Science.gov (United States)

    Song, Qi-Ying; Song, Jie-Yun; Wang, Yang; Wang, Shuo; Yang, Yi-De; Meng, Xiang-Rui; Ma, Jun; Wang, Hai-Jun; Wang, Yan

    2017-01-01

    This study aimed to examine associations of three single-nucleotide polymorphisms (SNPs) with obesity-related phenotypes in Chinese children. These SNPs were identified by a recent genome-wide association (GWA) study among European children. Given that varied genetic backgrounds across different ethnicity may result in different association, it is necessary to study these associations in a different ethnic population. A total of 3,922 children, including 2,191 normal-weight, 873 overweight and 858 obese children, from three independent studies were included in the study. Logistic and linear regressions were performed, and meta-analyses were conducted to assess the associations between the SNPs and obesity-related phenotypes. The pooled odds ratios of the A-allele of rs564343 in PACS1 for obesity and severe obesity were 1.180 (p = 0.03) and 1.312 (p = 0.004), respectively. We also found that rs564343 was nominally associated with BMI, BMI standard deviation score (BMI-SDS), waist circumference, and waist-to-height ratio (p obesity in a non-European population. This SNP was also found to be associated with common obesity and various obesity-related phenotypes in Chinese children, which had not been reported in the original study. The results demonstrated the value of conducting genetic researches in populations with different ethnicity. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

  13. Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3

    Science.gov (United States)

    Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E.

    2015-01-01

    The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ε4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3,500 subjects from 1,070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value = 3.98·10−08), rs1347297 in the gene OSBPL6 (P-value = 4.53·10−08), and rs1513625 near PDCL3 (P-value = 4.28·10−08). In addition, rs72953347 in OSBPL6 (P-value = 6.36·10−07) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value: 4.76·10−07; rs62400067, P-value: 3.54·10−07). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID:26830138

  14. Spectral analyses of systolic blood pressure and heart rate variability and their association with cognitive performance in elderly hypertensive subjects.

    Science.gov (United States)

    Santos, W B; Matoso, J M D; Maltez, M; Gonçalves, T; Casanova, M; Moreira, I F H; Lourenço, R A; Monteiro, W D; Farinatti, P T V; Soares, P P; Oigman, W; Neves, M F T; Correia, M L G

    2015-08-01

    Systolic hypertension is associated with cognitive decline in the elderly. Altered blood pressure (BP) variability is a possible mechanism of reduced cognitive performance in elderly hypertensives. We hypothesized that altered beat-to-beat systolic BP variability is associated with reduced global cognitive performance in elderly hypertensive subjects. In exploratory analyses, we also studied the correlation between diverse discrete cognitive domains and indices of systolic BP and heart rate variability. Disproving our initial hypothesis, we have shown that hypertension and low education, but not indices of systolic BP and heart rate variability, were independent predictors of lower global cognitive performance. However, exploratory analyses showed that the systolic BP variability in semi-upright position was an independent predictor of matrix reasoning (B = 0.08 ± .03, P-value = 0.005), whereas heart rate variability in semi-upright position was an independent predictor of the executive function score (B = -6.36 ± 2.55, P-value = 0.02). We conclude that myogenic vascular and sympathetic modulation of systolic BP do not contribute to reduced global cognitive performance in treated hypertensive subjects. Nevertheless, our results suggest that both systolic BP and heart rate variability might be associated with modulation of frontal lobe cognitive domains, such as executive function and matrix reasoning.

  15. Methods for analysing cardiovascular studies with repeated measures

    NARCIS (Netherlands)

    Cleophas, T. J.; Zwinderman, A. H.; van Ouwerkerk, B. M.

    2009-01-01

    Background. Repeated measurements in a single subject are generally more similar than unrepeated measurements in different subjects. Unrepeated analyses of repeated data cause underestimation of the treatment effects. Objective. To review methods adequate for the analysis of cardiovascular studies

  16. Genome-wide association analyses identify variants in developmental genes associated with hypospadias

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Carstensen, Lisbeth

    2014-01-01

    Hypospadias is a common congenital condition in boys in which the urethra opens on the underside of the penis. We performed a genome-wide association study on 1,006 surgery-confirmed hypospadias cases and 5,486 controls from Denmark. After replication genotyping of an additional 1,972 cases and 1...

  17. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  18. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    Science.gov (United States)

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  19. Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal.

    Science.gov (United States)

    Delgado, Dayana A; Zhang, Chenan; Chen, Lin S; Gao, Jianjun; Roy, Shantanu; Shinkle, Justin; Sabarinathan, Mekala; Argos, Maria; Tong, Lin; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Sarwar, Golam; Shahriar, Hasan; Rahman, Mahfuzar; Yunus, Mohammad; Jasmine, Farzana; Kibriya, Muhammad G; Ahsan, Habibul; Pierce, Brandon L

    2018-01-01

    Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry. This study aims to enhance our understanding of genetic determinants of TL across populations. We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes. Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10 -8 and P=6.4×10 -6 , respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10 -7 ) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 ( ZNF208 ) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only. In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

    DEFF Research Database (Denmark)

    Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon

    2011-01-01

    and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...... phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest....

  1. Pathway analyses implicate glial cells in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Laramie E Duncan

    Full Text Available The quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge.Ten publically available gene sets (pathways related to glia, mitochondria, and glutamate were tested for association to schizophrenia and bipolar disorder using MAGENTA as the primary analysis method. To determine the robustness of associations, secondary analyses were performed with: ALIGATOR, INRICH, and Set Screen. Data from the Psychiatric Genomics Consortium (PGC were used for all analyses. There were 1,068,286 SNP-level p-values for schizophrenia (9,394 cases/12,462 controls, and 2,088,878 SNP-level p-values for bipolar disorder (7,481 cases/9,250 controls.The Glia-Oligodendrocyte pathway was associated with schizophrenia, after correction for multiple tests, according to primary analysis (MAGENTA p = 0.0005, 75% requirement for individual gene significance and also achieved nominal levels of significance with INRICH (p = 0.0057 and ALIGATOR (p = 0.022. For bipolar disorder, Set Screen yielded nominally and method-wide significant associations to all three glial pathways, with strongest association to the Glia-Astrocyte pathway (p = 0.002.Consistent with findings of white matter abnormalities in schizophrenia by other methods of study, the Glia-Oligodendrocyte pathway was associated with schizophrenia in our genomic study. These findings suggest that the abnormalities of myelination observed in schizophrenia are at least in part due to inherited factors, contrasted with the alternative of purely environmental causes (e.g. medication effects or lifestyle. While not the primary purpose of our study

  2. Study on drug costs associated with COPD prescription medicine in Denmark.

    Science.gov (United States)

    Jakobsen, Marie; Anker, Niels; Dollerup, Jens; Poulsen, Peter Bo; Lange, Peter

    2013-10-01

    Spirometric studies of the general population estimate that 430 000 Danes have chronic obstructive pulmonary disease (COPD). COPD is mainly caused by smoking, and smoking cessation is the most important intervention to prevent disease progression. Cost-of-illness studies conclude that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. To analyse the societal costs associated with prescription medicine for COPD in Denmark. The study was designed as a nationwide retrospective register study of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who had been either hospitalised with a COPD diagnosis or had at least one prescription for drugs primarily used for COPD. The study population comprised 166 462 individuals of which 97 916 were alive on 31 December 2010. The average annual drug costs (R03) were DKK 7842 (EUR 1055) per patient in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70 000-75 000 (EUR 9416-10 089) per patient (2010 prices). The costs associated with prescription medicine for COPD in Denmark are significant. © 2012 John Wiley & Sons Ltd.

  3. Genome wide association study identifies KCNMA1 contributing to human obesity

    DEFF Research Database (Denmark)

    Jiao, Hong; Arner, Peter; Hoffstedt, Johan

    2011-01-01

    Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population....... Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity....

  4. Inverse association between atopy and melanoma: A case-control study

    NARCIS (Netherlands)

    Marasigan, V. (Vivien); M.-A. Morren (Marie-Anne); J. Lambert; Medaer, K. (Karen); Fieuws, S. (Steffen); T.E.C. Nijsten (Tamar); Garmyn, M. (Marjan)

    2017-01-01

    textabstractHeightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by

  5. Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders

    NARCIS (Netherlands)

    Cichon, S.; Craddock, N.; Daly, M.J.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.P.; Sklar, P.; Sullivan, P.F.; Boomsma, D.I.; de Geus, E.J.C.; Posthuma, D.; Willemsen, G.

    2009-01-01

    Objective: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. Method: A literature review was carried out, power and other issues

  6. Genomewide association studies: history, rationale, and prospects for psychiatric disorders.

    NARCIS (Netherlands)

    Franke, B.; Buitelaar, J.K.; Cichon, S.; Craddock, N.; Daly, M.; Faraone, S.V.; Gejman, P.V.; Kelsoe, J.; Lehner, T.; Levinson, D.F.; Moran, A.; Sklar, P.; Sullivan, P.F.

    2009-01-01

    OBJECTIVE: The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. METHOD: A literature review was carried out, power and other issues

  7. Audio-visual perception of 3D cinematography: an fMRI study using condition-based and computation-based analyses.

    Directory of Open Access Journals (Sweden)

    Akitoshi Ogawa

    Full Text Available The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard "condition-based" designs, as well as "computational" methods based on the extraction of time-varying features of the stimuli (e.g. motion. Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround, 3D with monaural sound (3D-Mono, 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computation-based analyses. The latter assessed where activity co-varied with visual disparity signals and the complexity of auditory multi-sources signals. The blocked analyses associated 3D viewing with the activation of the dorsal and lateral occipital cortex and superior parietal lobule, while the surround sounds activated the superior and middle temporal gyri (S/MTG. The computation-based analyses revealed the effects of absolute disparity in dorsal occipital and posterior parietal cortices and of disparity gradients in the posterior middle temporal gyrus plus the inferior frontal gyrus. The complexity of the surround sounds was associated with activity in specific sub-regions of S/MTG, even after accounting for changes of sound intensity. These results demonstrate that the processing of naturalistic audio-visual signals entails an extensive set of visual and auditory areas, and that computation-based analyses can track the contribution of complex spatial aspects characterizing such life

  8. Audio-visual perception of 3D cinematography: an fMRI study using condition-based and computation-based analyses.

    Science.gov (United States)

    Ogawa, Akitoshi; Bordier, Cecile; Macaluso, Emiliano

    2013-01-01

    The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard "condition-based" designs, as well as "computational" methods based on the extraction of time-varying features of the stimuli (e.g. motion). Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround), 3D with monaural sound (3D-Mono), 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computation-based analyses. The latter assessed where activity co-varied with visual disparity signals and the complexity of auditory multi-sources signals. The blocked analyses associated 3D viewing with the activation of the dorsal and lateral occipital cortex and superior parietal lobule, while the surround sounds activated the superior and middle temporal gyri (S/MTG). The computation-based analyses revealed the effects of absolute disparity in dorsal occipital and posterior parietal cortices and of disparity gradients in the posterior middle temporal gyrus plus the inferior frontal gyrus. The complexity of the surround sounds was associated with activity in specific sub-regions of S/MTG, even after accounting for changes of sound intensity. These results demonstrate that the processing of naturalistic audio-visual signals entails an extensive set of visual and auditory areas, and that computation-based analyses can track the contribution of complex spatial aspects characterizing such life-like stimuli.

  9. Mouse and human genetic analyses associate kalirin with ventral striatal activation during impulsivity and with alcohol misuse

    Directory of Open Access Journals (Sweden)

    Yolanda ePeña-Oliver

    2016-04-01

    Full Text Available Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behaviour in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioural data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org, to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of <0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologues of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol-experience. There was a significant overall association between the human homologues of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking.

  10. The association between nocturia and nocturnal polyuria in clinical and epidemiological studies: a systematic review and meta-analyses.

    Science.gov (United States)

    Hofmeester, Ilse; Kollen, Boudewijn J; Steffens, Martijn G; Bosch, J L H Ruud; Drake, Marcus J; Weiss, Jeffrey P; Blanker, Marco H

    2014-04-01

    We determined the relationship between nocturia and nocturnal polyuria. The PubMed® and Embase® databases were searched for studies written in English, German, French or Dutch with original data on adult participants in an investigation of the relationship between nocturia and nocturnal polyuria. A meta-analysis of the difference in mean nocturnal voiding frequencies between patients with and without nocturnal polyuria was conducted. Nocturnal polyuria risk was compared between participants with and without nocturia, and the resulting odds ratio was subsequently converted to relative risk with 95% CIs. From 511 references identified we selected 78 publications of 66 studies, 15 of which met the inclusion criteria for this study. Quality scores of studies were generally high for internal validity but low for external validity. In 7 studies (1,416 participants) we estimated a standardized mean difference of 0.59 (95% CI 0.29-0.89) for nocturnal voids between nocturnal polyuria and nonnocturnal polyuria cases. In 8 other studies (with 2,320 participants) we calculated a pooled OR of 4.99 (3.92-6.37) for nocturnal polyuria in individuals with nocturia. The corresponding RR, based on a nocturnal polyuria risk in the pooled population of 63.8%, was 1.41 (1.37-1.44). The association between nocturia and nocturnal polyuria is apparent and robust. However, the clinical importance of the association appears to be less obvious than previously suggested based on single studies. The observed high prevalence of nocturnal polyuria, as a result of the applied International Continence Society definition, may be responsible for this discrepancy. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Genetic association study of common mitochondrial variants on body fat mass.

    Directory of Open Access Journals (Sweden)

    Tie-Lin Yang

    Full Text Available Mitochondria play a central role in ATP production and energy metabolism. Previous studies suggest that common variants in mtDNA are associated with several common complex diseases, including obesity. To test the hypothesis that common mtDNA variants influence obesity-related phenotypes, including BMI and body fat mass, we genotyped a total of 445 mtSNPs across the whole mitochondrial genome in a large sample of 2,286 unrelated Caucasian subjects. 72 of these 445 mtSNPs passed quality control criteria, and were used for subsequent analyses. We also classified all subjects into nine common European haplogroups. Association analyses were conducted for both BMI and body fat mass with single mtSNPs and mtDNA haplogroups. Two mtSNPs, mt4823 and mt8873 were detected to be significantly associated with body fat mass, with adjusted P values of 4.94 × 10⁻³ and 4.58 × 10⁻², respectively. The minor alleles mt4823 C and mt8873 A were associated with reduced fat mass values and the effect size (β was estimated to be 3.52 and 3.18, respectively. These two mtSNPs also achieved nominally significant levels for association with BMI. For haplogroup analyses, we found that haplogroup X was strongly associated with both BMI (adjusted P = 8.31 × 10⁻³ and body fat mass (adjusted P = 5.67×10⁻⁴ Subjects classified as haplogroup X had lower BMI and fat mass values, with the β estimated to be 2.86 and 6.03, respectively. Our findings suggest that common variants in mitochondria might play a role in variations of body fat mass. Further molecular and functional studies will be needed to clarify the potential mechanism.

  12. Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans

    Directory of Open Access Journals (Sweden)

    Kidambi Srividya

    2012-04-01

    Full Text Available Abstract Background A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives. Methods We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13 found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications. Results For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204 showed borderline association (p = 0.006 with hypertension status using recessive model and systolic blood pressure (p = 0.02, but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002. In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant. Conclusions This study highlights the importance of replication to confirm the validity of genome wide

  13. Connecting the dots, genome-wide association studies in substance use

    NARCIS (Netherlands)

    Nivard, M.G.; Verweij, K.J.H.; Minica, C.C.; Treur, J.L.; Vink, J.M.; Boomsma, D.I.

    2016-01-01

    The recent genome-wide association (GWA) meta-analysis of lifetime cannabis use by the International Cannabis Consortium marks a milestone in the study of the genetics of cannabis use. Similar milestones for the genetics of substance use were the GWA meta-analyses of four smoking related traits, of

  14. LOD score exclusion analyses for candidate genes using random population samples.

    Science.gov (United States)

    Deng, H W; Li, J; Recker, R R

    2001-05-01

    While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes with random population samples. We develop a LOD score approach for exclusion analyses of candidate genes with random population samples. Under this approach, specific genetic effects and inheritance models at candidate genes can be analysed and if a LOD score is < or = - 2.0, the locus can be excluded from having an effect larger than that specified. Computer simulations show that, with sample sizes often employed in association studies, this approach has high power to exclude a gene from having moderate genetic effects. In contrast to regular association analyses, population admixture will not affect the robustness of our analyses; in fact, it renders our analyses more conservative and thus any significant exclusion result is robust. Our exclusion analysis complements association analysis for candidate genes in random population samples and is parallel to the exclusion mapping analyses that may be conducted in linkage analyses with pedigrees or relative pairs. The usefulness of the approach is demonstrated by an application to test the importance of vitamin D receptor and estrogen receptor genes underlying the differential risk to osteoporotic fractures.

  15. Psychosocial Factors Related to Lateral and Medial Epicondylitis: Results From Pooled Study Analyses.

    Science.gov (United States)

    Thiese, Matthew S; Hegmann, Kurt T; Kapellusch, Jay; Merryweather, Andrew; Bao, Stephen; Silverstein, Barbara; Tang, Ruoliang; Garg, Arun

    2016-06-01

    The goal is to assess the relationships between psychosocial factors and both medial and lateral epicondylitis after adjustment for personal and job physical exposures. One thousand eight hundred twenty-four participants were included in pooled analyses. Ten psychosocial factors were assessed. One hundred twenty-one (6.6%) and 34 (1.9%) participants have lateral and medial epicondylitis, respectively. Nine psychosocial factors assessed had significant trends or associations with lateral epicondylitis, the largest of which was between physical exhaustion after work and lateral epicondylitis with and odds ratio of 7.04 (95% confidence interval = 2.02 to 24.51). Eight psychosocial factors had significant trends or relationships with medial epicondylitis, with the largest being between mental exhaustion after work with an odds ratio of 6.51 (95% confidence interval = 1.57 to 27.04). The breadth and strength of these associations after adjustment for confounding factors demonstrate meaningful relationships that need to be further investigated in prospective analyses.

  16. The MAFLA (Mississippi, Alabama, Florida) Study, Grain Size Analyses

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The MAFLA (Mississippi, Alabama, Florida) Study was funded by NOAA as part of the Outer Continental Shelf Program. Dr. L.J. Doyle produced grain size analyses in the...

  17. Frontotemporal dementia and its subtypes: a genome-wide association study.

    Science.gov (United States)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A; Rohrer, Jonathan D; Ramasamy, Adaikalavan; Kwok, John B J; Dobson-Stone, Carol; Brooks, William S; Schofield, Peter R; Halliday, Glenda M; Hodges, John R; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Mann, David M A; Grafman, Jordan; Morris, Christopher M; Attems, Johannes; Griffiths, Timothy D; McKeith, Ian G; Thomas, Alan J; Pietrini, P; Huey, Edward D; Wassermann, Eric M; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; St George-Hyslop, Peter; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, Johannes C M; Uphill, James; Collinge, John; Mead, Simon; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowski, John Q; van der Zee, Julie; Deschamps, William; Van Langenhove, Tim; Cruts, Marc; Van Broeckhoven, Christine; Cappa, Stefano F; Le Ber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E; Hjermind, Lena E; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N; Fox, Nick C; Warren, Jason D; Spillantini, Maria Grazia; Morris, Huw R; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Knopman, David; Josephs, Keith A; Boeve, Bradley F; Parisi, Joseph E; Seeley, William W; Miller, Bruce L; Karydas, Anna M; Rosen, Howard; van Swieten, John C; Dopper, Elise G P; Seelaar, Harro; Pijnenburg, Yolande A L; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, Massimo; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebert, Florence; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B; Hardy, John; Momeni, Parastoo

    2014-07-01

    Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10(-8)) single-nucleotide polymorphisms. We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data

  18. Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: cross-sectional analyses from the KEEPS study

    Directory of Open Access Journals (Sweden)

    Huang Gary

    2012-07-01

    Full Text Available Abstract Background The published literature regarding the relationships between retinol-binding protein 4 (RBP4 and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard western blot analysis of RBP4 levels. Methods Full-length serum RBP4 levels were measured by western blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT, and coronary artery calcification (CAC. Results The mean age of women was 52.9 (± 2.6 years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5 μg/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient = 0.10; P = 0.01, but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients ≤0.06, P > 0.05. Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile. However, a squared RBP4 term in regression modeling was non-significant (P = 0.10. Conclusions In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis. Trial registration ClinicalTrials.gov number NCT

  19. Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies.

    Science.gov (United States)

    Catalá-López, Ferrán; Hutton, Brian; Driver, Jane A; Page, Matthew J; Ridao, Manuel; Valderas, José M; Alonso-Arroyo, Adolfo; Forés-Martos, Jaume; Martínez, Salvador; Gènova-Maleras, Ricard; Macías-Saint-Gerons, Diego; Crespo-Facorro, Benedicto; Vieta, Eduard; Valencia, Alfonso; Tabarés-Seisdedos, Rafael

    2017-04-04

    The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used

  20. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    NARCIS (Netherlands)

    Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F.; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L.; Rivadeneira, Fernando; Uitterlinden, Andre G.; Palmer, Colin N. A.; Doney, Alex S. F.; Willemsen, Gonneke; Smit, Johannes H.; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L.; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L.; Fowkes, Gerard R.; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H.; Basart, Hanneke V.; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E.; Boehm, Bernhard O.; Peters, Annette; Pramstaller, Peter P.; Province, Michael A.; Borecki, Ingrid B.; Hastie, Nicholas D.; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M.; Bergman, Richard N.; Collins, Francis S.; Tuomilehto, Jaakko; Watanabe, Richard M.; de Geus, Eco J. C.; Penninx, Brenda W.; Hofman, Albert; Oostra, Ben A.; Psaty, Bruce M.; Vollenweider, Peter; Wilson, James F.; Wright, Alan F.; Hovingh, G. Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K. E.; Kyvik, Kirsten O.; Kaprio, Jaakko; Price, Jackie F.; Dedoussis, George V.; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R.; van Duijn, Cornelia M.; Morris, Andrew D.; Toenjes, Anke; Peyser, Patricia A.; Beilby, John P.; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R.; Schwarz, Peter E. H.; Lakka, Timo A.; Rauramaa, Rainer; Adair, Linda S.; Smith, George Davey; Spector, Tim D.; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Boomsma, Dorret I.; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L.; Sattar, Naveed; Harris, Tamara B.; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L.; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J.; Bouatia-Naji, Nabila; McCarthy, Mark I.; Franks, Paul W.; Meigs, James B.; Teslovich, Tanya M.; Florez, Jose C.; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes

  1. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    DEFF Research Database (Denmark)

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes...

  2. RELAP5 analyses and support of Oconee-1 PTS studies

    International Nuclear Information System (INIS)

    Charlton, T.R.

    1983-01-01

    The integrity of a reactor vessel during a severe overcooling transient with primary system pressurization is a current safety concern and has been identified as an Unresolved Safety Issue(USI) A-49 by the US Nuclear Regulatory Commission (NRC). Resolution of USI A-49, denoted as Pressurized Thermal Shock (PTS), is being examined by the US NRC sponsored PTS integration study. In support of this study, the Idaho National Engineering Laboratory (INEL) has performed RELAP5/MOD1.5 thermal-hydraulic analyses of selected overcooling transients. These transient analyses were performed for the Oconee-1 pressurized water reactor (PWR), which is Babcock and Wilcox designed nuclear steam supply system

  3. Ecogeographical associations between climate and human body composition: analyses based on anthropometry and skinfolds.

    Science.gov (United States)

    Wells, Jonathan C K

    2012-02-01

    In the 19th century, two "ecogeographical rules" were proposed hypothesizing associations of climate with mammalian body size and proportions. Data on human body weight and relative leg length support these rules; however, it is unknown whether such associations are attributable to lean tissue (the heat-producing component) or fat (energy stores). Data on weight, height, and two skinfold thickness were obtained from the literature for 137 nonindustrialized populations, providing 145 male and 115 female individual samples. A variety of indices of adiposity and lean mass were analyzed. Preliminary analyses indicated secular increases in skinfolds in men but not women, and associations of age and height with lean mass in both sexes. Decreasing annual temperature was associated with increasing body mass index (BMI), and increasing triceps but not subscapular skinfold. After adjusting for skinfolds, decreasing temperature remained associated with increasing BMI. These results indicate that colder environments favor both greater peripheral energy stores, and greater lean mass. Contrasting results for triceps and subscapular skinfolds might be due to adaptive strategies either constraining central adiposity in cold environments to reduce cardiovascular risk, or favoring central adiposity in warmer environments to maintain energetic support of the immune system. Polynesian populations were analyzed separately and contradicted all of the climate trends, indicating support for the hypothesis that they are cold-adapted despite occupying a tropical region. It is unclear whether such associations emerge through natural selection or through trans-generational and life-course plasticity. These findings nevertheless aid understanding of the wide variability in human physique and adiposity. Copyright © 2011 Wiley Periodicals, Inc.

  4. Genomewide Association Scan of a Mortality Associated Endophenotype for a Long and Healthy Life in the Long Life Family Study

    DEFF Research Database (Denmark)

    Singh, Jatinder; Minster, Ryan L; Schupf, Nicole

    2017-01-01

    Background: Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. Methods: Using data from the Long Life Family Study, we performed genomewide association analyses on an endopheno...

  5. Ecology and Evolution of Diatom-Associated Cyanobacteria Through Genetic Analyses

    OpenAIRE

    Hilton, Jason Andrew

    2014-01-01

    Primary production in a large fraction of the surface ocean communities is limited by the availability of nitrogen (N). Heterocyst-forming cyanobacteria associated with diatoms of the genera Hemiaulus, Rhizosolenia, and Chaetoceros can dominate surface communities throughout the global oceans, and are an important source of N to these communities. Additionally, these unique associations are directly linked to a highly efficient carbon export system. In order to study the nature and evolution ...

  6. Genome-wide Association Studies for Female Fertility Traits in Chinese and Nordic Holsteins.

    Science.gov (United States)

    Liu, Aoxing; Wang, Yachun; Sahana, Goutam; Zhang, Qin; Liu, Lin; Lund, Mogens Sandø; Su, Guosheng

    2017-08-16

    Reduced female fertility could cause considerable economic loss and has become a worldwide problem in the modern dairy industry. The objective of this study was to detect quantitative trait loci (QTL) for female fertility traits in Chinese and Nordic Holsteins using various strategies. First, single-trait association analyses were performed for female fertility traits in Chinese and Nordic Holsteins. Second, the SNPs with P-value Nordic Holsteins. Third, the summary statistics from single-trait association analyses were combined into meta-analyses to: (1) identify common QTL for multiple fertility traits within each Holstein population; (2) detect SNPs which were associated with a female fertility trait across two Holstein populations. A large numbers of QTL were discovered or confirmed for female fertility traits. The QTL segregating at 31.4~34.1 Mb on BTA13, 48.3~51.9 Mb on BTA23 and 34.0~37.6 Mb on BTA28 shared between Chinese and Nordic Holsteins were further ascertained using a validation approach and meta-analyses. Furthermore, multiple novel variants identified in Chinese Holsteins were validated with Nordic data as well as meta-analyses. The genes IL6R, SLC39A12, CACNB2, ZEB1, ZMIZ1 and FAM213A were concluded to be strong candidate genes for female fertility in Holsteins.

  7. Chocolate intake is associated with better cognitive function: The Maine-Syracuse Longitudinal Study.

    Science.gov (United States)

    Crichton, Georgina E; Elias, Merrill F; Alkerwi, Ala'a

    2016-05-01

    Chocolate and cocoa flavanols have been associated with improvements in a range of health complaints dating from ancient times, and has established cardiovascular benefits. Less is known about the effects of chocolate on neurocognition and behaviour. The aim of this study was to investigate whether chocolate intake was associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors. Cross-sectional analyses were undertaken on 968 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intake was related to cognitive performance, measured with an extensive battery of neuropsychological tests. More frequent chocolate consumption was significantly associated with better performance on the Global Composite score, Visual-Spatial Memory and Organization, Working Memory, Scanning and Tracking, Abstract Reasoning, and the Mini-Mental State Examination. With the exception of Working Memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors. Prospective analyses revealed no association between cognitive function and chocolate intake measured up to 18 years later. Further intervention trials and longitudinal studies are needed to explore relations between chocolate, cocoa flavanols and cognition, and the underlying causal mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Association of abdominal fat with serum amylase in an older cohort: The Baltimore Longitudinal Study of Aging.

    Science.gov (United States)

    Dias, Jenny Pena; Schrack, Jennifer A; Shardell, Michelle D; Egan, Josephine M; Studenski, Stephanie

    2016-06-01

    Abdominal fat is a major determinant of metabolic diseases in older individuals. Obesity and diabetes are associated with low serum amylase (SA) levels, but the association between SA and metabolic disease is poorly understood. We investigated the association of low SA with diabetes and sex-specific associations of serum amylase with abdominal fat in older adults. In community-dwelling volunteers from the Baltimore Longitudinal Study of Aging (778 participants, age 66.8±13.6years), we assessed abdominal fat by computed tomography and diabetes status using the American Diabetes Association criteria. Linear regression analyses assessed the cross-sectional associations between abdominal fat and SA, and logistic regression assessed the odds of diabetes, given low SA. In unadjusted analyses, individuals in the lowest SA quartile (abdominal subcutaneous adipose tissue (SAT, dm(2)) or BMI. In adjusted analyses, VAT and SAT were significantly associated with SA in both sexes. Among women, SA was more strongly associated with VAT than with SAT or BMI; VAT (β=-0.117±0.048, Pabdominal visceral fat. In women, SA was more strongly associated with VAT than with BMI or SAT. These findings provide motivation for future mechanistic studies on SA's role in metabolic diseases. Published by Elsevier Ireland Ltd.

  9. Poor replication validity of biomedical association studies reported by newspapers.

    Science.gov (United States)

    Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings

  10. Poor replication validity of biomedical association studies reported by newspapers.

    Directory of Open Access Journals (Sweden)

    Estelle Dumas-Mallet

    Full Text Available To investigate the replication validity of biomedical association studies covered by newspapers.We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking and a non-lifestyle category (e.g. genetic risk. Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses.Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8% and subsequent (58/600 9.7% lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1% than subsequent ones (45/3718 1.2%. Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48 than subsequent ones (29/45 and than lifestyle studies (31/63. Psychiatric studies covered by newspapers were less often confirmed (10/38 than the neurological (26/41 or somatic (40/77 ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim.Journalists preferentially cover initial findings

  11. Poor replication validity of biomedical association studies reported by newspapers

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists

  12. Frontotemporal dementia and its subtypes: a genome-wide association study

    Science.gov (United States)

    Ferrari, Raffaele; Hernandez, Dena G; Nalls, Michael A; Rohrer, Jonathan D; Ramasamy, Adaikalavan; Kwok, John B J; Dobson-Stone, Carol; Brooks, William S; Schofield, Peter R; Halliday, Glenda M; Hodges, John R; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Waldö, Maria Landqvist; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Mann, David M A; Grafman, Jordan; Morris, Christopher M; Attems, Johannes; Griffiths, Timothy D; McKeith, Ian G; Thomas, Alan J; Pietrini, P; Huey, Edward D; Wassermann, Eric M; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; George-Hyslop, Peter St; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B; Schlachetzki, J C M; Uphill, James; Collinge, John; Mead, S; Danek, Adrian; Van Deerlin, Vivianna M; Grossman, Murray; Trojanowsk, John Q; van der Zee, Julie; Deschamps, William; Van Langenhove, Tim; Cruts, Marc; Van Broeckhoven, Christine; Cappa, Stefano F; Le Ber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E; Hjermind, Lena E; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N; Fox, Nick C; Warren, Jason D; Spillantini, Maria Grazia; Morris, Huw R; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Knopman, David; Josephs, Keith A; Boeve, Bradley F; Parisi, Joseph E; Seeley, William W; Miller, Bruce L; Karydas, Anna M; Rosen, Howard; van Swieten, John C; Dopper, Elise G P; Seelaar, Harro; Pijnenburg, Yolande AL; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A; Franceschi, M; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebert, Florence; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B; Hardy, John; Momeni, Parastoo

    2014-01-01

    Summary Background Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. All participants had European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) and suggestive single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8) that encompassed the HLA locus at 6p21.3 in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC, for the behavioural FTD subtype. Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation incis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and possibly to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of

  13. A genome-wide association study of corneal astigmatism: The CREAM Consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts we...

  14. A genome-wide association study of corneal astigmatism: The CREAM Consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts wer...

  15. A genome-wide association study of corneal astigmatism: The CREAM Consortium.

    OpenAIRE

    Shah, Rupal L; Li, Qing; Zhao, Wanting; Tedja, Milly S; Tideman, J Willem L; Khawaja, Anthony P; Fan, Qiao; Yazar, Seyhan; Williams, Katie M; Verhoeven, Virginie J M; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J

    2018-01-01

    Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry...

  16. A genome-wide association study of corneal astigmatism : The CREAM Consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohor...

  17. A genome-wide association study of corneal astigmatism:The CREAM consortium

    OpenAIRE

    Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.

    2018-01-01

    Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohort...

  18. The Influence of Study-Level Inference Models and Study Set Size on Coordinate-Based fMRI Meta-Analyses

    Directory of Open Access Journals (Sweden)

    Han Bossier

    2018-01-01

    Full Text Available Given the increasing amount of neuroimaging studies, there is a growing need to summarize published results. Coordinate-based meta-analyses use the locations of statistically significant local maxima with possibly the associated effect sizes to aggregate studies. In this paper, we investigate the influence of key characteristics of a coordinate-based meta-analysis on (1 the balance between false and true positives and (2 the activation reliability of the outcome from a coordinate-based meta-analysis. More particularly, we consider the influence of the chosen group level model at the study level [fixed effects, ordinary least squares (OLS, or mixed effects models], the type of coordinate-based meta-analysis [Activation Likelihood Estimation (ALE that only uses peak locations, fixed effects, and random effects meta-analysis that take into account both peak location and height] and the amount of studies included in the analysis (from 10 to 35. To do this, we apply a resampling scheme on a large dataset (N = 1,400 to create a test condition and compare this with an independent evaluation condition. The test condition corresponds to subsampling participants into studies and combine these using meta-analyses. The evaluation condition corresponds to a high-powered group analysis. We observe the best performance when using mixed effects models in individual studies combined with a random effects meta-analysis. Moreover the performance increases with the number of studies included in the meta-analysis. When peak height is not taken into consideration, we show that the popular ALE procedure is a good alternative in terms of the balance between type I and II errors. However, it requires more studies compared to other procedures in terms of activation reliability. Finally, we discuss the differences, interpretations, and limitations of our results.

  19. Association of Facebook Use With Compromised Well-Being: A Longitudinal Study.

    Science.gov (United States)

    Shakya, Holly B; Christakis, Nicholas A

    2017-02-01

    Face-to-face social interactions enhance well-being. With the ubiquity of social media, important questions have arisen about the impact of online social interactions. In the present study, we assessed the associations of both online and offline social networks with several subjective measures of well-being. We used 3 waves (2013, 2014, and 2015) of data from 5,208 subjects in the nationally representative Gallup Panel Social Network Study survey, including social network measures, in combination with objective measures of Facebook use. We investigated the associations of Facebook activity and real-world social network activity with self-reported physical health, self-reported mental health, self-reported life satisfaction, and body mass index. Our results showed that overall, the use of Facebook was negatively associated with well-being. For example, a 1-standard-deviation increase in "likes clicked" (clicking "like" on someone else's content), "links clicked" (clicking a link to another site or article), or "status updates" (updating one's own Facebook status) was associated with a decrease of 5%-8% of a standard deviation in self-reported mental health. These associations were robust to multivariate cross-sectional analyses, as well as to 2-wave prospective analyses. The negative associations of Facebook use were comparable to or greater in magnitude than the positive impact of offline interactions, which suggests a possible tradeoff between offline and online relationships. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

    DEFF Research Database (Denmark)

    Fatemifar, Ghazaleh; Hoggart, Clive J; Paternoster, Lavinia

    2013-01-01

    Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth......' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex...

  1. Dairy shows different associations with abdominal and BMI-defined overweight: Cross-sectional analyses exploring a variety of dairy products.

    Science.gov (United States)

    Brouwer-Brolsma, E M; Sluik, D; Singh-Povel, C M; Feskens, E J M

    2018-05-01

    Previous studies have suggested weight-regulatory properties for several dairy nutrients, but population-based studies on dairy and body weight are inconclusive. We explored cross-sectional associations between dairy consumption and indicators of overweight. We included 114,682 Dutch adults, aged ≥18 years. Dairy consumption was quantified by a food frequency questionnaire. Abdominal overweight was defined as waist circumference (WC) ≥88 cm (women) or ≥102 cm (men) (n = 37,391), overweight as BMI ≥25-30 kg/m 2 (n = 44,772) and obesity as BMI ≥30 kg/m 2 (n = 15,339). Associations were quantified by logistic (abdominal overweight, no/yes), multinomial logistic (BMI-defined overweight and obesity) and linear regression analyses (continuous measures of WC and BMI), and they were adjusted for relevant covariates. Total dairy showed a positive association with abdominal overweight (OR Q1 ref vs. Q5: 1.09; 95% CI: 1.04-1.14) and with BMI-defined overweight (OR Q5 1.13; 95% CI: 1.08-1.18) and obesity (OR Q5 1.09; 95% CI: 1.02-1.16). Skimmed, semi-skimmed and non-fermented dairy also showed positive associations with overweight categories. Full-fat dairy showed an inverse association with overweight and obesity (OR Q5 for obesity: 0.78; 95% CI: 0.73-0.83). Moreover, inverse associations were observed for yoghurt and custard and positive associations for milk, buttermilk, flavoured yoghurt drinks, cheese and cheese snacks. Fermented dairy, curd cheese and Dutch cheese did not show a consistent association with overweight categories. Total, skimmed, semi-skimmed and non-fermented dairy; milk; buttermilk; flavoured yoghurt drinks; total cheese and cheese snacks showed a positive association with overweight categories, whereas full-fat dairy, custard and yoghurt showed an inverse association with overweight categories. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human

  2. Genome-wide association study of pathological gambling.

    Science.gov (United States)

    Lang, M; Leménager, T; Streit, F; Fauth-Bühler, M; Frank, J; Juraeva, D; Witt, S H; Degenhardt, F; Hofmann, A; Heilmann-Heimbach, S; Kiefer, F; Brors, B; Grabe, H-J; John, U; Bischof, A; Bischof, G; Völker, U; Homuth, G; Beutel, M; Lind, P A; Medland, S E; Slutske, W S; Martin, N G; Völzke, H; Nöthen, M M; Meyer, C; Rumpf, H-J; Wurst, F M; Rietschel, M; Mann, K F

    2016-08-01

    Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence. Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence. No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value=6.63×10(-3)); 5'-adenosine monophosphate-activated protein kinase signalling (P-value=9.57×10(-3)); and apoptosis (P-value=1.75×10(-2)) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status. The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Genome-wide association study identifies genetic loci associated with iron deficiency.

    Directory of Open Access Journals (Sweden)

    Christine E McLaren

    2011-03-01

    Full Text Available The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS was performed using DNA collected from white men aged≥25 y and women≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS Study with serum ferritin (SF≤12 µg/L (cases and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women. Regression analysis was used to examine the association between case-control status (336 cases, 343 controls and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10(-7 for all. An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P=7.0×10(-9, corrected P=0.012 was replicated within the VA samples (observed P=0.012. Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification.

  4. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses

    Science.gov (United States)

    Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

    2016-02-01

    We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

  5. Challenges in reproducibility of genetic association studies: lessons learned from the obesity field.

    Science.gov (United States)

    Li, A; Meyre, D

    2013-04-01

    A robust replication of initial genetic association findings has proved to be difficult in human complex diseases and more specifically in the obesity field. An obvious cause of non-replication in genetic association studies is the initial report of a false positive result, which can be explained by a non-heritable phenotype, insufficient sample size, improper correction for multiple testing, population stratification, technical biases, insufficient quality control or inappropriate statistical analyses. Replication may, however, be challenging even when the original study describes a true positive association. The reasons include underpowered replication samples, gene × gene, gene × environment interactions, genetic and phenotypic heterogeneity and subjective interpretation of data. In this review, we address classic pitfalls in genetic association studies and provide guidelines for proper discovery and replication genetic association studies with a specific focus on obesity.

  6. Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study.

    Science.gov (United States)

    Martin, Joanna; Tilling, Kate; Hubbard, Leon; Stergiakouli, Evie; Thapar, Anita; Davey Smith, George; O'Donovan, Michael C; Zammit, Stanley

    2016-06-15

    Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

  7. Pathways from fertility history to later life health: Results from analyses of the English Longitudinal Study of Ageing

    Directory of Open Access Journals (Sweden)

    Emily Grundy

    2015-01-01

    Full Text Available Background: Previous research shows associations between fertility histories and later life health. The childless, those with large families, and those with a young age at entry to parenthood generally have higher mortality and worse health than parents of two or three children. These associations are hypothesised to reflect a range of biosocial influences, but underlying mechanisms are poorly understood. Objective: To identify pathways from fertility histories to later life health by examining mediation through health-related behaviours, social support and strain, and wealth. Additionally to examine mediation through allostatic load - an indicator of multisystem physical dysregulation, hypothesised to be an outcome of chronic stress. Methods: Associations between fertility histories, mediators, and outcomes were analysed using path models. Data were drawn from the English Longitudinal Study of Ageing. Outcomes studied were a measure of allostatic load based on 9 biomarkers and self-reported long-term illness which limited activities. Results: Early parenthood (Conclusions: In England early parenthood and larger family size are associated with less wealth and poorer health behaviours and this accounts for much of the association with health. At least part of this operates through stress-related physiological dysfunction (allostatic load.

  8. An association study of suicide and candidate genes in the serotonergic system

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette N; Flint, Tracey J; Foldager, Leslie

    2013-01-01

    Introduction: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other...... populations. Method: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within...... the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Ttyptophan Hydroxylase I and II (TPH1 and TPH2) genes. Results: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory...

  9. JUPITER and satellites: Clinical implications of the JUPITER study and its secondary analyses.

    Science.gov (United States)

    Kostapanos, Michael S; Elisaf, Moses S

    2011-07-26

    THE JUSTIFICATION FOR THE USE OF STATINS IN PREVENTION: an intervention trial evaluating rosuvastatin (JUPITER) study was a real breakthrough in primary cardiovascular disease prevention with statins, since it was conducted in apparently healthy individuals with normal levels of low-density lipoprotein cholesterol (LDL-C JUPITER, rosuvastatin was associated with significant reductions in cardiovascular outcomes as well as in overall mortality compared with placebo. In this paper the most important secondary analyses of the JUPITER trial are discussed, by focusing on their novel findings regarding the role of statins in primary prevention. Also, the characteristics of otherwise healthy normocholesterolemic subjects who are anticipated to benefit more from statin treatment in the clinical setting are discussed. Subjects at "intermediate" or "high" 10-year risk according to the Framingham score, those who exhibit low post-treatment levels of both LDL-C (JUPITER added to our knowledge that statins may be effective drugs in the primary prevention of cardiovascular disease in normocholesterolemic individuals at moderate-to-high risk. Also, statin treatment may reduce the risk of venous thromboembolism and preserve renal function. An increase in physician-reported diabetes represents a major safety concern associated with the use of the most potent statins.

  10. Common genetic variants associated with disease from genome-wide association studies are mutually exclusive in prostate cancer and rheumatoid arthritis.

    Science.gov (United States)

    Orozco, Gisela; Goh, Chee L; Al Olama, Ali Amin; Benlloch-Garcia, Sara; Govindasami, Koveela; Guy, Michelle; Muir, Kenneth R; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Kote-Jarai, Zsofia; Easton, Douglas F; Eyre, Steve; Eeles, Rosalind A

    2013-06-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The link between inflammation and cancer has long been reported and inflammation is thought to play a role in the pathogenesis of many cancers, including prostate cancer (PrCa). Over the last 5 years, genome-wide association studies (GWAS) have reported numerous susceptibility loci that predispose individuals to many different traits. The present study aims to ascertain if there are common genetic risk profiles that might predispose individuals to both PrCa and the autoimmune inflammatory condition, rheumatoid arthritis. These results could have potential public heath impact in terms of screening and chemoprevention. To investigate if potential common pathways exist for the pathogenesis of autoimmune disease and prostate cancer (PrCa). To ascertain if the single nucleotide polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being associated with susceptibility to PrCa are also associated with susceptibility to the autoimmune disease rheumatoid arthritis (RA). The original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was expanded to include a total of 3221 cases and 5272 controls. In all, 37 germline autosomal SNPs at genome-wide significance associated with PrCa risk were identified from a UK/Australian PrCa GWAS. Allele frequencies were compared for these 37 SNPs between RA cases and controls using a chi-squared trend test and corrected for multiple testing (Bonferroni). In all, 33 SNPs were able to be analysed in the RA dataset. Proxies could not be located for the SNPs in 3q26, 5p15 and for two SNPs in 17q12. After applying a Bonferroni correction for the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained statistically significant evidence for association (P = 6 × 10(-4) ; odds ratio [OR] = 1.15, 95% CI: 1.06-1.24); this has also been associated with psoriasis. However, further analyses showed that the association of this allele was due to

  11. Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.

    Directory of Open Access Journals (Sweden)

    Joanna M Biernacka

    Full Text Available Genome-wide association studies (GWAS have revealed many single nucleotide polymorphisms (SNPs associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017. Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI = 0.80 (0.66, 0.95; women: OR (95%CI = 0.83 (0.66, 1.03. We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081, and independently in the alcohol-dependent cases (p = 0.046. Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

  12. Associations between residential traffic noise exposure and smoking habits and alcohol consumption-A population-based study.

    Science.gov (United States)

    Roswall, Nina; Christensen, Jeppe Schultz; Bidstrup, Pernille Envold; Raaschou-Nielsen, Ole; Jensen, Steen Solvang; Tjønneland, Anne; Sørensen, Mette

    2018-05-01

    Traffic noise stresses and disturbs sleep. It has been associated with various diseases, and has recently also been associated with lifestyle. Hence, the association between traffic noise and disease could partly operate via a pathway of lifestyle habits, including smoking and alcohol intake. We investigated associations between modelled residential traffic noise and smoking habits and alcohol consumption. In a cohort of 57,053 participants, we performed cross-sectional analyses using data from a baseline questionnaire (1993-97), and longitudinal analyses of change between baseline and follow-up (2000-02). Smoking status (never, former, current) and intensity (tobacco, g/day) and alcohol consumption (g/day) was self-reported at baseline and follow-up. Address history from 1987-2002 for all participants were found in national registries, and road traffic and railway noise was modelled 1 and 5 years before enrolment, and from baseline to follow-up. Analyses were performed using logistic and linear regression, and adjusted for demographics, socioeconomic variables, leisure-time sports, and noise from the opposite source (road/railway). Road traffic noise exposure 5 years before baseline was positively associated with alcohol consumption (adjusted difference per 10 dB: 1.38 g/day, 95% confidence interval (CI): 1.10-1.65), smoking intensity (adjusted difference per 10 dB: 0.40 g/day, 95% CI: 0.19-0.61), and odds for being a current vs. never/former smoker at baseline (odds ratio (OR): 1.14; 95% CI: 1.10-1.17). In longitudinal analyses, we found no association between road traffic noise and change in smoking and alcohol habits. Railway noise was not associated with smoking habits and alcohol consumption, neither in cross-sectional nor in longitudinal analyses. The study suggests that long-term exposure to residential road traffic is associated with smoking habits and alcohol consumption, albeit only in cross-sectional, but not in longitudinal analyses. Copyright

  13. Distribution-analytical techniques in the study of AD/HD: Delta plot analyses reveal deficits in response inhibition that are eliminated by methylphenidate treatment

    NARCIS (Netherlands)

    Ridderinkhof, K.R.; Scheres, A.; Oosterlaan, J.; Sergeant, J.A.

    2005-01-01

    The authors highlight the utility of distribution-analytical techniques in the study of individual differences and clinical disorders. Cognitive deficits associated with attention-deficit/hyperactivity disorder (AD/HD) were examined by using delta-plot analyses of performance data (reaction time and

  14. A population-based study of associations between current posttraumatic stress symptoms and current fatigue.

    Science.gov (United States)

    Lerdal, Anners; Lee, Kathryn A; Rokne, Berit; Knudsen, Øistein; Wahl, Astrid K; Dahl, Alv A

    2010-10-01

    This study explores current experience with posttraumatic stress disorder (PTSD) symptoms and other variables (sociodemographic, mental distress, somatic morbidity, self-rated health, and quality of life [QoL]) in relation to fatigue. A representative sample of the Norwegian population (N = 3,944) was invited to participate in a mailed survey, and 1,857 (47%) returned valid responses on the questionnaire that included the Fatigue Severity Scale and the Posttraumatic Symptom Scale-10. Posttraumatic stress disorder symptoms showed a strong association with fatigue in univariate (β = .41) and multivariate analyses (β = .33). Associations between psychosocial health variables, QoL, and fatigue were confirmed. However, PTSD symptoms showed the strongest association with fatigue in the analyses. Findings need to be replicated in other population samples and in clinical samples with PTSD and fatigue.

  15. Independent associations of dairy and calcium intakes with colorectal cancers in the Adventist Health Study-2 cohort.

    Science.gov (United States)

    Tantamango-Bartley, Yessenia; Knutsen, Synnove F; Jaceldo-Siegl, Karen; Fan, Jing; Mashchak, Andrew; Fraser, Gary E

    2017-10-01

    Results associating dairy and Ca intakes with colorectal cancer (CRC) risk have been mixed. Most previous analyses have suffered from confounding between dairy and Ca intakes. We examined independent associations between these variables, also dairy foods, and CRC incidence in a population with a large range of dairy intakes. Adventist Health Study-2 is a cohort study where subjects were enrolled 2002-2007. Proportional hazard regression analyses were performed to estimate hazard ratios (HR). Regression calibration was used to correct for dietary measurement error. The population lived in all states of the USA. There were 77712 analytic subjects, all of whom were Seventh-day Adventists. Much of their dietary Ca came from non-dairy sources. During a mean follow-up of 7·8 years, 380 incident colon cancer and 111 incident rectal cancer cases were observed. Comparing extreme quintiles of intake in measurement error-corrected analyses, dairy intake (HR=0·31; 95 % CI 0·09, 0·88), independent of total Ca, was inversely related with risk of rectal cancer but gave little indication of association with colon cancer. However, total Ca intake (independent of dairy) was associated with risk of colon cancer (HR=0·55; 95 % CI 0·28, 0·98) and there was little indication of association with rectal cancer. Traditional regression analyses and associations with macronutrients from dairy generally supported these results. Milk intake was also negatively associated with CRC (HR=0·63; 95 % CI 0·43, 0·89). Dairy intake may decrease the risk of rectal cancer, and Ca may reduce risk of colon cancer and CRC.

  16. Using the gene ontology to scan multilevel gene sets for associations in genome wide association studies.

    Science.gov (United States)

    Schaid, Daniel J; Sinnwell, Jason P; Jenkins, Gregory D; McDonnell, Shannon K; Ingle, James N; Kubo, Michiaki; Goss, Paul E; Costantino, Joseph P; Wickerham, D Lawrence; Weinshilboum, Richard M

    2012-01-01

    Gene-set analyses have been widely used in gene expression studies, and some of the developed methods have been extended to genome wide association studies (GWAS). Yet, complications due to linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes per gene-set, have plagued current approaches, often leading to ad hoc "fixes." To overcome some of the current limitations, we developed a general approach to scan GWAS SNP data for both gene-level and gene-set analyses, building on score statistics for generalized linear models, and taking advantage of the directed acyclic graph structure of the gene ontology when creating gene-sets. However, other types of gene-set structures can be used, such as the popular Kyoto Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes, and genes into gene-sets, but assures that positive and negative effects of genes on a trait do not cancel. To control for multiple testing of many gene-sets, we use an efficient computational strategy that accounts for LD and provides accurate step-down adjusted P-values for each gene-set. Application of our methods to two different GWAS provide guidance on the potential strengths and weaknesses of our proposed gene-set analyses. © 2011 Wiley Periodicals, Inc.

  17. Importance of frequency dependent magnetoresistance measurements in analysing the intrinsicality of magnetodielectric effect: A case study

    Science.gov (United States)

    Rai, Hari Mohan; Saxena, Shailendra K.; Mishra, Vikash; Kumar, Rajesh; Sagdeo, P. R.

    2017-08-01

    Magnetodielectric (MD) materials have attracted considerable attention due to their intriguing physics and potential future applications. However, the intrinsicality of the MD effect is always a major concern in such materials as the MD effect may arise also due to the MR (magnetoresistance) effect. In the present case study, we report an experimental approach to analyse and separate the intrinsic and MR dominated contributions of the MD phenomenon. For this purpose, polycrystalline samples of LaGa1-xAxO3 (A = Mn/Fe) have been prepared by solid state reaction method. The purity of their structural phase (orthorhombic) has been validated by refining the X-ray diffraction data. The RTMD (room temperature MD) response has been recorded over a frequency range of 20 Hz to 10 MHz. In order to analyse the intrinsicality of the MD effect, FDMR (frequency dependent MR) by means of IS (impedance spectroscopy) and dc MR measurements in four probe geometry have been carried out at RT. A significant RTMD effect has been observed in selected Mn/Fe doped LaGaO3 (LGO) compositions. The mechanism of MR free/intrinsic MD effect, observed in Mn/Fe doped LGO, has been understood speculatively in terms of modified cell volume associated with the reorientation/retransformation of spin-coupled Mn/Fe orbitals due to the application of magnetic field. The present analysis suggests that in order to justify the intrinsic/resistive origin of the MD phenomenon, FDMR measurements are more useful than measuring only dc MR or analysing the trends of magnetic field dependent change in the dielectric constant and tanδ. On the basis of the present case study, we propose that IS (FDMR) alone can be used as an effective experimental tool to detect and analyse the resistive and intrinsic parts contributing to the MD phenomenon.

  18. Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease: Longitudinal Analyses in the UK Biobank Study.

    Science.gov (United States)

    Tikkanen, Emmi; Gustafsson, Stefan; Ingelsson, Erik

    2018-04-09

    Background -Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases. Methods -We estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4-6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference. Results -Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77- 0.81; HR, 0.95; 95% CI, 0.93-0.97; and HR, 0.68; 95% CI, 0.63-0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73- 0.76; HR, 0.93; 95% CI, 0.91-0.95; and HR, 0.60; 95% CI, 0.56-0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group ( P trend fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38-0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30-0.55) among individuals at high genetic risk for these diseases. Conclusions - Fitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases.

  19. Unexpected associated microalgal diversity in the lichen Ramalina farinacea is uncovered by pyrosequencing analyses.

    Directory of Open Access Journals (Sweden)

    Patricia Moya

    Full Text Available The current literature reveals that the intrathalline coexistence of multiple microalgal taxa in lichens is more common than previously thought, and additional complexity is supported by the coexistence of bacteria and basidiomycete yeasts in lichen thalli. This replaces the old paradigm that lichen symbiosis occurs between a fungus and a single photobiont. The lichen Ramalina farinacea has proven to be a suitable model to study the multiplicity of microalgae in lichen thalli due to the constant coexistence of Trebouxia sp. TR9 and T. jamesii in long-distance populations. To date, studies involving phycobiont diversity within entire thalli are based on Sanger sequencing, but this method seems to underestimate the diversity. Here, we aim to analyze both the microalgal diversity and its community structure in a single thallus of the lichen R. farinacea by applying a 454 pyrosequencing approach coupled with a careful ad hoc-performed protocol for lichen sample processing prior to DNA extraction. To ascertain the reliability of the pyrosequencing results and the applied bioinformatics pipeline results, the thalli were divided into three sections (apical, middle and basal zones, and a mock community sample was used. The developed methodology allowed 40448 filtered algal reads to be obtained from a single lichen thallus, which encompassed 31 OTUs representative of different microalgae genera. In addition to corroborating the coexistence of the two Trebouxia sp. TR9 and T. jamesii taxa in the same thallus, this study showed a much higher microalgal diversity associated with the lichen. Along the thallus ramifications, we also detected variations in phycobiont distribution that might correlate with different microenvironmental conditions. These results highlight R. farinacea as a suitable material for studying microalgal diversity and further strengthen the concept of lichens as multispecies microecosystems. Future analyses will be relevant to

  20. Factors Associated with Remission of Eczema in Children: a Population-based Follow-up Study.

    OpenAIRE

    von Kobyletzki, Laura; Bornehag, Carl-Gustaf; Breeze, Elizabeth; Larsson, Malin; Boman Lindström, Cecilia; Svensson, Åke

    2014-01-01

    The aim of this study was to analyse factors associated with remission of atopic dermatitis (AD) in childhood. A population-based AD cohort of 894 children aged 1-3 years from a cross-sectional baseline study in 2000 was followed up in 2005. The association between remission, background, health, lifestyle, and environmental variables was estimated with crude and multivariable logistic regression. At follow-up, 52% of the children had remission. Independent factors at baseline predicting remis...

  1. Associations between the peer support relationship, service satisfaction and recovery-oriented outcomes: a correlational study.

    Science.gov (United States)

    Thomas, Elizabeth C; Salzer, Mark S

    2017-12-18

    The working alliance between non-peer providers and mental health consumers is associated with positive outcomes. It is hypothesized that this factor, in addition to other active support elements, is also positively related to peer support service outcomes. This study evaluates correlates of the peer-to-peer relationship and its unique association with service satisfaction and recovery-oriented outcomes. Participants were 46 adults with serious mental illnesses taking part in a peer-brokered self-directed care intervention. Pearson correlation analyses examined associations among peer relationship factors, services-related variables and recovery-oriented outcomes (i.e. empowerment, recovery and quality of life). Hierarchical multiple regression analyses evaluated associations between relationship factors and outcomes over time, controlling for other possible intervention effects. The peer relationship was not related to number of contacts. There were robust associations between the peer relationship and service satisfaction and some recovery-oriented outcomes at 24-months, but not at 12-months. These associations were not explained by other possible intervention effects. This study contributes to a better understanding of the positive, unique association between the peer-to-peer relationship and outcomes, similar to what is found in non-peer-delivered interventions. Implications for program administrators and policymakers seeking to integrate peer specialists into mental health service systems are discussed.

  2. Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

    Science.gov (United States)

    Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

    2017-01-01

    Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk

  3. Associations of indoor carbon dioxide concentrations, VOCS, environmental susceptibilities with mucous membrane and lower respiratory sick building syndrome symptoms in the BASE study: Analyses of the 100 building dataset

    Energy Technology Data Exchange (ETDEWEB)

    Apte, M.G.; Erdmann, C.A.

    2002-10-01

    Using the 100 office-building Building Assessment Survey and Evaluation (BASE) Study dataset, we performed multivariate logistic regression analyses to quantify the associations between indoor minus outdoor CO{sub 2} (dCO{sub 2}) concentrations and mucous membrane (MM) and lower respiratory system (Lresp) Sick Building Syndrome (SBS) symptoms, adjusting for age, sex, smoking status, presence of carpet in workspace, thermal exposure, relative humidity, and a marker for entrained automobile exhaust. Using principal components analysis we identified a number of possible sources of 73 measured volatile organic compounds in the office buildings, and assessed the impact of these VOCs on the probability of presenting the SBS symptoms. Additionally we included analysis adjusting for the risks for predisposition of having SBS symptoms associated with the allergic, asthmatic, and environmentally sensitive subpopulations within the office buildings. Adjusted odds ratios (ORs) for statistically significant, dose-dependant associations (p<0.05) for dry eyes, sore throat, nose/sinus congestion, and wheeze symptoms with 100-ppm increases in dCO{sub 2} ranged from 1.1 to 1.2. These results suggest that increases in the ventilation rates per person among typical office buildings will, on average significantly reduce the prevalence of several SBS symptoms, up to 80%, even when these buildings meet the existing ASHRAE ventilation standards for office buildings. VOC sources were observed to play an role in direct association with mucous membrane and lower respiratory irritation, and possibly to be indirectly involved in indoor chemical reactions with ozone that produce irritating compounds associated with SBS symptoms. O-xylene, possibly emitted from furniture coatings was associated with shortness of breath (OR at the maximum concentration = 8, p < 0.05). The environmental sensitivities of a large subset of the office building population add to the overall risk of SBS symptoms (ORs

  4. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    NARCIS (Netherlands)

    A.D. Børglum; D. Demontis; J. Grove (Jakob); J. Pallesen (J.); M.V. Hollegaard (Mads V); C.B. Pedersen (C.); A. Hedemand (A.); M. Mattheisen (Manuel); A.G. Uitterlinden (André); M. Nyegaard (M.); T.F. Orntoft (Torben); C. Wiuf (Carsten); M. Didriksen (Michael); M. Nordentoft (M.); M.M. Nö then (M.); M. Rietschel (Marcella); R.A. Ophoff (Roel); S. Cichon (Sven); R.H. Yolken (Robert); D.M. Hougaard (David); P.B. Mortensen; O. Mors

    2014-01-01

    textabstractGenetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all

  5. Trend analyses in the health behaviour in school-aged children study

    DEFF Research Database (Denmark)

    Schnohr, Christina W; Molcho, Michal; Rasmussen, Mette

    2015-01-01

    are considered. When analysing trends, researchers must be able to assess whether a change in prevalence is an expression of an actual change in the observed outcome, whether it is a result of methodological artefacts, or whether it is due to changes in the conceptualization of the outcome by the respondents....... CONCLUSION: The article present recommendations to take a number of the considerations into account. The considerations imply methodological challenges, which are core issues in undertaking trend analyses....... collecting data from adolescents aged 11-15 years, on a broad variety of health determinants and health behaviours. RESULTS: A number of methodological challenges have stemmed from the growth of the HBSC-study, in particular given that the study has a focus on monitoring trends. Some of those challenges...

  6. Associations between self-esteem, general self-efficacy and approaches to studying in occupational therapy students: A cross-sectional study

    OpenAIRE

    Bonsaksen, Tore; Sadeghi, Talieh; Thørrisen, Mikkel Magnus

    2017-01-01

    The aim of this study was to explore associations between self-esteem, general self-efficacy, and the deep, strategic, and surface approaches to studying. Norwegian occupational therapy students (n = 125) completed questionnaires measuring study approaches, self-esteem, and general self-efficacy. Regression analyses were used to explore the direct relationships between self-esteem, general self-efficacy and the approaches to studying, after controlling for age, gender, prior higher education,...

  7. Bayesian graphical models for genomewide association studies.

    Science.gov (United States)

    Verzilli, Claudio J; Stallard, Nigel; Whittaker, John C

    2006-07-01

    As the extent of human genetic variation becomes more fully characterized, the research community is faced with the challenging task of using this information to dissect the heritable components of complex traits. Genomewide association studies offer great promise in this respect, but their analysis poses formidable difficulties. In this article, we describe a computationally efficient approach to mining genotype-phenotype associations that scales to the size of the data sets currently being collected in such studies. We use discrete graphical models as a data-mining tool, searching for single- or multilocus patterns of association around a causative site. The approach is fully Bayesian, allowing us to incorporate prior knowledge on the spatial dependencies around each marker due to linkage disequilibrium, which reduces considerably the number of possible graphical structures. A Markov chain-Monte Carlo scheme is developed that yields samples from the posterior distribution of graphs conditional on the data from which probabilistic statements about the strength of any genotype-phenotype association can be made. Using data simulated under scenarios that vary in marker density, genotype relative risk of a causative allele, and mode of inheritance, we show that the proposed approach has better localization properties and leads to lower false-positive rates than do single-locus analyses. Finally, we present an application of our method to a quasi-synthetic data set in which data from the CYP2D6 region are embedded within simulated data on 100K single-nucleotide polymorphisms. Analysis is quick (<5 min), and we are able to localize the causative site to a very short interval.

  8. Monte Carlo parameter studies and uncertainty analyses with MCNP5

    International Nuclear Information System (INIS)

    Brown, F. B.; Sweezy, J. E.; Hayes, R.

    2004-01-01

    A software tool called mcnp p study has been developed to automate the setup, execution, and collection of results from a series of MCNP5 Monte Carlo calculations. This tool provides a convenient means of performing parameter studies, total uncertainty analyses, parallel job execution on clusters, stochastic geometry modeling, and other types of calculations where a series of MCNP5 jobs must be performed with varying problem input specifications. (authors)

  9. Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott

    Full Text Available Genome-wide association studies (GWAS have successfully identified common genetic variants that contribute to breast cancer risk. Discovering additional variants has become difficult, as power to detect variants of weaker effect with present sample sizes is limited. An alternative approach is to look for variants associated with quantitative traits that in turn affect disease risk. As exposure to high circulating estradiol and testosterone, and low sex hormone-binding globulin (SHBG levels is implicated in breast cancer etiology, we conducted GWAS analyses of plasma estradiol, testosterone, and SHBG to identify new susceptibility alleles. Cancer Genetic Markers of Susceptibility (CGEMS data from the Nurses' Health Study (NHS, and Sisters in Breast Cancer Screening data were used to carry out primary meta-analyses among ~1600 postmenopausal women who were not taking postmenopausal hormones at blood draw. We observed a genome-wide significant association between SHBG levels and rs727428 (joint β = -0.126; joint P = 2.09 × 10(-16, downstream of the SHBG gene. No genome-wide significant associations were observed with estradiol or testosterone levels. Among variants that were suggestively associated with estradiol (P<10(-5, several were located at the CYP19A1 gene locus. Overall results were similar in secondary meta-analyses that included ~900 NHS current postmenopausal hormone users. No variant associated with estradiol, testosterone, or SHBG at P<10(-5 was associated with postmenopausal breast cancer risk among CGEMS participants. Our results suggest that the small magnitude of difference in hormone levels associated with common genetic variants is likely insufficient to detectably contribute to breast cancer risk.

  10. Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses

    Science.gov (United States)

    van der Klift, Heleen M; Jansen, Anne M L; van der Steenstraten, Niki; Bik, Elsa C; Tops, Carli M J; Devilee, Peter; Wijnen, Juul T

    2015-01-01

    A subset of DNA variants causes genetic disease through aberrant splicing. Experimental splicing assays, either RT-PCR analyses of patient RNA or functional splicing reporter minigene assays, are required to evaluate the molecular nature of the splice defect. Here, we present minigene assays performed for 17 variants in the consensus splice site regions, 14 exonic variants outside these regions, and two deep intronic variants, all in the DNA mismatch-repair (MMR) genes MLH1, MSH2, MSH6, and PMS2, associated with Lynch syndrome. We also included two deep intronic variants in APC and PKD2. For one variant (MLH1 c.122A>G), our minigene assay and patient RNA analysis could not confirm the previously reported aberrant splicing. The aim of our study was to further investigate the concordance between minigene splicing assays and patient RNA analyses. For 30 variants results from patient RNA analyses were available, either performed by our laboratory or presented in literature. Some variants were deliberately included in this study because they resulted in multiple aberrant transcripts in patient RNA analysis, or caused a splice effect other than the prevalent exon skip. While both methods were completely concordant in the assessment of splice effects, four variants exhibited major differences in aberrant splice patterns. Based on the present and earlier studies, together showing an almost 100% concordance of minigene assays with patient RNA analyses, we discuss the weight given to minigene splicing assays in the current criteria proposed by InSiGHT for clinical classification of MMR variants. PMID:26247049

  11. Limitations and risks of meta-analyses of longevity studies

    DEFF Research Database (Denmark)

    Sebastiani, Paola; Bae, Harold; Gurinovich, Anastasia

    2017-01-01

    Searching for genetic determinants of human longevity has been challenged by the rarity of data sets with large numbers of individuals who have reached extreme old age, inconsistent definitions of the phenotype, and the difficulty of defining appropriate controls. Meta-analysis - a statistical...... method to summarize results from different studies - has become a common tool in genetic epidemiology to accrue large sample sizes for powerful genetic association studies. In conducting a meta-analysis of studies of human longevity however, particular attention must be made to the definition of cases...... and controls (including their health status) and on the effect of possible confounders such as sex and ethnicity upon the genetic effect to be estimated. We will show examples of how a meta-analysis can inflate the false negative rates of genetic association studies or it can bias estimates of the association...

  12. Summary of Prometheus Radiation Shielding Nuclear Design Analyses , for information

    International Nuclear Information System (INIS)

    J. Stephens

    2006-01-01

    This report transmits a summary of radiation shielding nuclear design studies performed to support the Prometheus project. Together, the enclosures and references associated with this document describe NRPCT (KAPL and Bettis) shielding nuclear design analyses done for the project

  13. Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications.

    Science.gov (United States)

    Erzurumluoglu, A Mesut; Baird, Denis; Richardson, Tom G; Timpson, Nicholas J; Rodriguez, Santiago

    2018-01-22

    Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics than in genetic epidemiology, although associations between Y-DNA haplogroups and several traits, including cardiometabolic traits, have been reported. In apparently homogeneous populations defined by principal component analyses, there is still Y-DNA haplogroup variation which will result from population history. Therefore, hidden stratification and/or differential phenotypic effects by Y-DNA haplogroups could exist. To test this, we hypothesised that stratifying individuals according to their Y-DNA haplogroups before testing for associations between autosomal single nucleotide polymorphisms (SNPs) and phenotypes will yield difference in association. For proof of concept, we derived Y-DNA haplogroups from 6537 males from two epidemiological cohorts, Avon Longitudinal Study of Parents and Children (ALSPAC) ( n = 5080; 816 Y-DNA SNPs) and the 1958 Birth Cohort ( n = 1457; 1849 Y-DNA SNPs), and studied the robust associations between 32 SNPs and body mass index (BMI), including SNPs in or near Fat Mass and Obesity-associated protein ( FTO ) which yield the strongest effects. Overall, no association was replicated in both cohorts when Y-DNA haplogroups were considered and this suggests that, for BMI at least, there is little evidence of differences in phenotype or SNP association by Y-DNA structure. Further studies using other traits, phenome-wide association studies (PheWAS), other haplogroups and/or autosomal SNPs are required to test the generalisability and utility of this approach.

  14. Dairy product consumption is associated with pre-diabetes and newly diagnosed type 2 diabetes in the Lifelines Cohort Study

    NARCIS (Netherlands)

    Brouwer, E.M.; Sluik, D.; Singh-Povel, C.M.; Feskens, E.J.M.

    2018-01-01

    Previous studies show associations between dairy product consumption and type 2 diabetes, but only a few studies conducted detailed analyses for a variety of dairy subgroups. Therefore, we examined cross-sectional associations of a broad variety of dairy subgroups with pre-diabetes and newly

  15. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents.

    Directory of Open Access Journals (Sweden)

    Tenna Ruest Haarmark Nielsen

    Full Text Available Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH and free thyroxine (fT4, respectively.This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity.Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5-24.7]. Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2-22.8]. Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses.No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 ∙ 10-16, FOXE1 (rs7847663: β = 0.223SD, p = 1.5 ∙ 10-20, NR3C2 (rs9968300: β = 0.194SD, p = 2.4 ∙ 10-11, VEGFA (rs2396083: β = 0.088SD, p = 2.2 ∙ 10-10. Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (p<0.0002. None of the TSH or fT4 associated SNPs were associated with obesity in our cohort, indicating no pleiotropic effects of these variants on obesity.In a group of Danish children and adolescents, four loci previously associated with plasma TSH concentrations in adults, were associated with plasma TSH

  16. Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two-sample bidirectional Mendelian randomization study.

    Science.gov (United States)

    Verweij, Karin J H; Treur, Jorien L; Vink, Jacqueline M

    2018-07-01

    Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine and cannabis use. Two-sample MR was employed to estimate bidirectional causal effects between four addictive substances: nicotine (smoking initiation and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units per week) and cannabis (initiation). Based on existing genome-wide association results we selected genetic variants associated with the exposure measure as an instrument to estimate causal effects. Where possible we applied sensitivity analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy. Most MR tests did not reveal causal associations. There was some weak evidence for a causal positive effect of genetically instrumented alcohol use on smoking initiation and of cigarettes per day on caffeine use, but these were not supported by the sensitivity analyses. There was also some suggestive evidence for a positive effect of alcohol use on caffeine use (only with MR-Egger) and smoking initiation on cannabis initiation (only with weighted median). None of the suggestive causal associations survived corrections for multiple testing. Two-sample Mendelian randomization analyses found little evidence for causal relationships between nicotine, alcohol, caffeine and cannabis use. © 2018 Society for the Study of Addiction.

  17. The relationship between insomnia with short sleep duration is associated with hypercholesterolemia: a cross-sectional study.

    Science.gov (United States)

    Lin, Chia-Ling; Tsai, Yu-Hsia; Yeh, Mei Chang

    2016-02-01

    To examine the association between insomnia with short sleep duration and hypercholesterolemia in Taiwanese adults. Previous studies mostly focused on the association between sleep duration and hyperlipidemia, but the results were not consistent. Besides, very few studies extensively examined the association between insomnia and hypercholesterolemia. This study hypothesized that insomnia with short sleep duration is associated with hypercholesterolemia. Secondary data analysis. This study analysed the latest database of the cross-sectional Nutrition and Health Survey in Taiwan which was released on 2011 (data collected between 2005-2008) and collected data using stratified three-staged probability sampling design. This study analysed 1533 participants aged between 19-64 (733 males and 800 females) and used logistic regression model to calculate the odds ratio and the 95% confidence interval of insomnia with short sleep duration to hypercholesterolemia. Controlled confounders included age, gender, sample weight, body mass index, waist circumference, fasting plasma glucose, hypertension and diabetes. Insomnia with 5-6 hours of sleep duration was significantly associated with hypercholesterolemia. The odds ratio of mild insomnia or moderate/severe insomnia with 5-6 hours of sleep duration to hypercholesterolemia was higher, compared with the reference group (without insomnia and >6 hours of sleep duration). Insomnia with short sleep duration was associated with increased odds of hypercholesterolemia. Caregivers in clinical practice should watch out for the effect brought by this novel factor. © 2015 John Wiley & Sons Ltd.

  18. Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.

    Directory of Open Access Journals (Sweden)

    Binod Neupane

    Full Text Available In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when

  19. Longitudinal changes in telomere length and associated genetic parameters in dairy cattle analysed using random regression models.

    Directory of Open Access Journals (Sweden)

    Luise A Seeker

    Full Text Available Telomeres cap the ends of linear chromosomes and shorten with age in many organisms. In humans short telomeres have been linked to morbidity and mortality. With the accumulation of longitudinal datasets the focus shifts from investigating telomere length (TL to exploring TL change within individuals over time. Some studies indicate that the speed of telomere attrition is predictive of future disease. The objectives of the present study were to 1 characterize the change in bovine relative leukocyte TL (RLTL across the lifetime in Holstein Friesian dairy cattle, 2 estimate genetic parameters of RLTL over time and 3 investigate the association of differences in individual RLTL profiles with productive lifespan. RLTL measurements were analysed using Legendre polynomials in a random regression model to describe TL profiles and genetic variance over age. The analyses were based on 1,328 repeated RLTL measurements of 308 female Holstein Friesian dairy cattle. A quadratic Legendre polynomial was fitted to the fixed effect of age in months and to the random effect of the animal identity. Changes in RLTL, heritability and within-trait genetic correlation along the age trajectory were calculated and illustrated. At a population level, the relationship between RLTL and age was described by a positive quadratic function. Individuals varied significantly regarding the direction and amount of RLTL change over life. The heritability of RLTL ranged from 0.36 to 0.47 (SE = 0.05-0.08 and remained statistically unchanged over time. The genetic correlation of RLTL at birth with measurements later in life decreased with the time interval between samplings from near unity to 0.69, indicating that TL later in life might be regulated by different genes than TL early in life. Even though animals differed in their RLTL profiles significantly, those differences were not correlated with productive lifespan (p = 0.954.

  20. Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Jingchun

    2011-09-01

    We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r(2)>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10 × 10(-3) and rs2274736, P=1.21 × 10(-3)). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45 × 10(-3) and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29 × 10(-3)). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43 × 10(-3)). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736\\/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.

  1. Dairy consumption is inversely associated with type 2 diabetes: dose-response meta-analysis of prospective cohort studies

    NARCIS (Netherlands)

    Gijsbers, L.; Geleijnse, J.M.; Soedamah-Muthu, S.S.

    2011-01-01

    Observational studies suggest an inverse association between dairy intake and incident type 2 diabetes, but the quantity of dairy is not known. Previous meta-analyses did not take into account the type of dairy product. Therefore, we examined dose-response associations between the intake of total

  2. Patterns and sources of adult personality development: growth curve analyses of the NEO PI-R scales in a longitudinal twin study.

    Science.gov (United States)

    Bleidorn, Wiebke; Kandler, Christian; Riemann, Rainer; Spinath, Frank M; Angleitner, Alois

    2009-07-01

    The present study examined the patterns and sources of 10-year stability and change of adult personality assessed by the 5 domains and 30 facets of the Revised NEO Personality Inventory. Phenotypic and biometric analyses were performed on data from 126 identical and 61 fraternal twins from the Bielefeld Longitudinal Study of Adult Twins (BiLSAT). Consistent with previous research, LGM analyses revealed significant mean-level changes in domains and facets suggesting maturation of personality. There were also substantial individual differences in the change trajectories of both domain and facet scales. Correlations between age and trait changes were modest and there were no significant associations between change and gender. Biometric extensions of growth curve models showed that 10-year stability and change of personality were influenced by both genetic as well as environmental factors. Regarding the etiology of change, the analyses uncovered a more complex picture than originally stated, as findings suggest noticeable differences between traits with respect to the magnitude of genetic and environmental effects. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  3. Association of sedentary behaviour with colon and rectal cancer: a meta-analysis of observational studies.

    Science.gov (United States)

    Cong, Y J; Gan, Y; Sun, H L; Deng, J; Cao, S Y; Xu, X; Lu, Z X

    2014-02-04

    Sedentary behaviour is ubiquitous in modern society. Emerging studies have focused on the health consequences of sedentary behaviour, including colorectal cancer, but whether sedentary behaviour is associated with the risks of colon and rectal cancer remains unclear. No systematic reviews have applied quantitative techniques to independently compute summary risk estimates. We aimed to conduct a meta-analysis to investigate this issue. We searched PubMed, Embase, and Google Scholar databases up to May 2013 to identify cohort and case-control studies that evaluated the association between sedentary behaviour and colon or rectal cancer. A random-effect model was used to pool the results of included studies. Publication bias was assessed by using Begg's funnel plot. Twenty-three studies with 63 reports were included in our meta-analysis. These groups included 4,324,462 participants (27,231 colon cancer cases and 13,813 rectal cancer cases). Sedentary behaviour was significantly associated with colon cancer (relative risk (RR): 1.30, 95% confidence interval (CI): 1.22-1.39) but did not have a statistically significant association with rectal cancer (RR 1.05, 95% CI, 0.98-1.13). Subgroup analyses suggested that the odds ratio (OR) of colon cancer was 1.46 (95% CI: 1.22-1.68) in the case-control studies, and the RR was 1.27 (95% CI: 1.18-1.36) in the cohort studies, the OR of rectal cancer was 1.06 (95% CI: 0.85-1.33) in the case-control studies, and the RR was 1.06 (95% CI, 1.01-1.12) in the cohort studies. Sedentary behaviour is associated with an increased risk of colon cancer. Subgroup analyses suggest a positive association between sedentary behaviour and risk of rectal cancer in cohort studies. Reducing sedentary behaviour is potentially important for the prevention of colorectal cancer.

  4. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    International Nuclear Information System (INIS)

    Fukunaga, Satoki; Kakehashi, Anna; Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki; Gi, Min; Wanibuchi, Hideki

    2015-01-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis

  5. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

  6. Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up.

    Science.gov (United States)

    Piirtola, Maarit; Kaprio, Jaakko; Kujala, Urho M; Heikkilä, Kauko; Koskenvuo, Markku; Svedberg, Pia; Silventoinen, Karri; Ropponen, Annina

    2016-08-04

    Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The association between years of education and leisure-time physical inactivity (inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were calculated using logistic and conditional (fixed-effects) regression models. Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding) of education on inactivity. However, the point estimates were lower than in the individual-level analyses. Adjustment for multiple covariates did not change these associations. Higher education is associated with lower odds of leisure-time physical inactivity during the three-decade follow

  7. Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up

    Directory of Open Access Journals (Sweden)

    Maarit Piirtola

    2016-08-01

    Full Text Available Abstract Background Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. Methods This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945–1957 (59 % women, of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %. The association between years of education and leisure-time physical inactivity (<1.5 metabolic equivalent hours/day was first analysed for each survey. Then, the role of education was investigated for 15-year and 35-year inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR with 95 % Confidence Intervals (CI were calculated using logistic and conditional (fixed-effects regression models. Results Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99 in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00 and OR 0.94 (95 % CI 0.91, 0.98, respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding of education on inactivity. However, the point estimates were lower than in the individual

  8. Association of Educational Level and Marital Status With Obesity: A Study of Chinese Twins.

    Science.gov (United States)

    Liao, Chunxiao; Gao, Wenjing; Cao, Weihua; Lv, Jun; Yu, Canqing; Wang, Shengfeng; Li, Chunxiao; Pang, Zengchang; Cong, Liming; Dong, Zhong; Wu, Fan; Wang, Hua; Wu, Xianping; Jiang, Guohong; Wang, Xiaojie; Wang, Binyou; Li, Liming

    2018-04-01

    The prevalence of overweight and obesity is growing rapidly in many countries. Socioeconomic inequalities might be important for this increase. The aim of this study was to determine associations of body mass index (BMI), overweight and obesity with educational level and marital status in Chinese twins. Participants were adult twins recruited through the Chinese National Twin Registry (CNTR), aged 18 to 79 years, and the sample comprised 10,448 same-sex twin pairs. Current height, weight, educational attainment, and marital status were self-reported. Regression analyses and structural equation models were conducted to evaluate BMI, overweight, and obesity associated with educational level and marital status in both sexes. At an individual level, both educational level and marital status were associated with higher BMI and higher risk of being overweight and obesity in men, while in women the effects of educational level on BMI were in the opposite direction. In within-Monozygotic (MZ) twin-pair analyses, the effects of educational level on BMI disappeared in females. Bivariate structural equation models showed that genetic factors and shared environmental confounded the relationship between education and BMI in females, whereas marital status was associated with BMI on account of significant positive unique environmental correlation apart in both sexes. The present data suggested that marital status and BMI were associated, independent of familiar factors, for both sexes of this study population, while common genetic and shared environmental factors contributed to education-associated disparities in BMI in females.

  9. Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population.

    Directory of Open Access Journals (Sweden)

    Po-Hsiu Kuo

    Full Text Available Autism spectrum disorder (ASD is a neurodevelopmental disorder with strong genetic components. Several recent genome-wide association (GWA studies in Caucasian samples have reported a number of gene regions and loci correlated with the risk of ASD--albeit with very little consensus across studies.A two-stage GWA study was employed to identify common genetic variants for ASD in the Taiwanese Han population. The discovery stage included 315 patients with ASD and 1,115 healthy controls, using the Affymetrix SNP array 6.0 platform for genotyping. Several gene regions were then selected for fine-mapping and top markers were examined in extended samples. Single marker, haplotype, gene-based, and pathway analyses were conducted for associations.Seven SNPs had p-values ranging from 3.4~9.9*10-6, but none reached the genome-wide significant level. Five of them were mapped to three known genes (OR2M4, STYK1, and MNT with significant empirical gene-based p-values in OR2M4 (p = 3.4*10(-5 and MNT (p = 0.0008. Results of the fine-mapping study showed single-marker associations in the GLIS1 (rs12082358 and rs12080993 and NAALADL2 (rs3914502 and rs2222447 genes, and gene-based associations for the OR2M3-OR2T5 (olfactory receptor genes, p = 0.02, and GLIPR1/KRR1 gene regions (p = 0.015. Pathway analyses revealed important pathways for ASD, such as olfactory and G protein-coupled receptors signaling pathways.We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism.

  10. Relationships between menstrual and menopausal attitudes and associated demographic and health characteristics: the Hilo Women's Health Study.

    Science.gov (United States)

    Morrison, Lynn A; Sievert, Lynnette L; Brown, Daniel E; Rahberg, Nichole; Reza, Angela

    2010-07-01

    The objective of this study was to examine the relation of menstrual attitudes to menopausal attitudes and the demographic and health characteristics associated with each. This cross-sectional study consisted of a randomly selected sample of 1,824 respondents aged 16 to 100 years in multi-ethnic Hilo, Hawai'i. Women completed questionnaires for demographic and health information, such as age, ethnicity, education, residency in Hawai'i, menopausal status, exercise, and attitudes toward menstruation and menopause. Women more often chose positive terms, such as "natural," to describe menstruation (60.8%) and menopause (59.4%). In bivariate analyses, post-menopausal women were significantly more likely to have positive menstrual and menopausal attitudes than pre-menopausal women. Factor analyses were used to cluster attitudes followed by linear regression to identify demographic characteristics associated with factor scores. Asian-American ethnicity, higher education, reporting more exercise, and growing up outside of Hawai'i were associated with positive menstrual attitudes. Higher education, older age, post-menopausal status, growing up outside of Hawai'i and having hot flashes were associated with positive menopausal attitudes. Bivariate correlation analyses suggested significant associations between factor scores for menstrual and menopausal attitudes. Both negative and positive menstrual attitudes were positively correlated with the anticipation of menopause, although negative attitudes toward menstruation were negatively correlated with menopause as a positive, natural life event. Demographic variables, specifically education and where one grows up, influenced women's attitudes toward menstruation and menopause and should be considered for inclusion in subsequent multi-ethnic studies. Further research is also warranted in assessing the relationship between menstrual and menopausal attitudes.

  11. ATHENA/INTRA analyses for ITER, NSSR-2

    International Nuclear Information System (INIS)

    Shen, Kecheng; Eriksson, John; Sjoeberg, A.

    1999-02-01

    The present report is a summary report including thermal-hydraulic analyses made at Studsvik Eco and Safety AB for the ITER NSSR-2 safety documentation. The objective of the analyses was to reveal the safety characteristics of various heat transfer systems at specified operating conditions and to indicate the conditions for which there were obvious risks of jeopardising the structural integrity of the coolant systems. In the latter case also some analyses were made to indicate conceivable mitigating measures for maintaining the integrity.The analyses were primarily concerned with the First Wall and Divertor heat transfer systems. Several enveloping transients were analysed with associated specific flow and heat load boundary conditions. The analyses were performed with the ATHENA and INTRA codes

  12. ATHENA/INTRA analyses for ITER, NSSR-2

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Kecheng; Eriksson, John; Sjoeberg, A

    1999-02-01

    The present report is a summary report including thermal-hydraulic analyses made at Studsvik Eco and Safety AB for the ITER NSSR-2 safety documentation. The objective of the analyses was to reveal the safety characteristics of various heat transfer systems at specified operating conditions and to indicate the conditions for which there were obvious risks of jeopardising the structural integrity of the coolant systems. In the latter case also some analyses were made to indicate conceivable mitigating measures for maintaining the integrity.The analyses were primarily concerned with the First Wall and Divertor heat transfer systems. Several enveloping transients were analysed with associated specific flow and heat load boundary conditions. The analyses were performed with the ATHENA and INTRA codes 8 refs, 14 figs, 15 tabs

  13. Genome-wide association study of smoking initiation and current smoking

    DEFF Research Database (Denmark)

    Vink, Jacqueline M; Smit, August B; de Geus, Eco J C

    2009-01-01

    For the identification of genes associated with smoking initiation and current smoking, genome-wide association analyses were carried out in 3497 subjects. Significant genes that replicated in three independent samples (n = 405, 5810, and 1648) were visualized into a biologically meaningful network......) and cell-adhesion molecules (e.g., CDH23). We conclude that a network-based genome-wide association approach can identify genes influencing smoking behavior....

  14. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers

    Science.gov (United States)

    Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega del Vecchyo, Vicente Diego; Chiang, Charleston W. K.; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M.; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

    2015-01-01

    We report ~17.6M genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from prior sequencing-based compilations and enriched for predicted functional consequence. Furthermore, ~76K variants common in our sample (frequency >5%) are rare elsewhere (Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. Fourteen signals, including two major new loci, were observed for lipid levels, and 19, including two novel loci, for inflammatory markers. New associations would be missed in analyses based on 1000 Genomes data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

  15. GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia

    NARCIS (Netherlands)

    Chen, X.; Lee, G.; Maher, B. S.; Fanous, A. H.; Chen, J.; Zhao, Z.; Guo, A.; van den Oord, E.; Sullivan, P. F.; Shi, J.; Levinson, D. F.; Gejman, P. V.; Sanders, A.; Duan, J.; Owen, M. J.; Craddock, N. J.; O'Donovan, M. C.; Blackman, J.; Lewis, D.; Kirov, G. K.; Qin, W.; Schwab, S.; Wildenauer, D.; Chowdari, K.; Nimgaonkar, V.; Straub, R. E.; Weinberger, D. R.; O'Neill, F. A.; Walsh, D.; Bronstein, M.; Darvasi, A.; Lencz, T.; Malhotra, A. K.; Rujescu, D.; Giegling, I.; Werge, T.; Hansen, T.; Ingason, A.; Nöethen, M. M.; Rietschel, M.; Cichon, S.; Djurovic, S.; Andreassen, O. A.; Cantor, R. M.; Ophoff, R.; Corvin, A.; Morris, D. W.; Gill, M.; Pato, C. N.; Pato, M. T.; Macedo, A.; Gurling, H. M. D.; McQuillin, A.; Pimm, J.; Hultman, C.; Lichtenstein, P.; Sklar, P.; Purcell, S. M.; Scolnick, E.; St Clair, D.; Blackwood, D. H. R.; Kendler, K. S.; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez; O'Donovan, Michael C.; Kirov, George K.; Craddock, Nick J.; Holmans, Peter A.; Williams, Nigel M.; Georgieva, Lyudmila; Nikolov, Ivan; Norton, N.; Williams, H.; Toncheva, Draga; Milanova, Vihra; Owen, Michael J.; Hultman, Christina M.; Lichtenstein, Paul; Thelander, Emma F.; Sullivan, Patrick; Morris, Derek W.; O'Dushlaine, Colm T.; Kenny, Elaine; Quinn, Emma M.; Gill, Michael; Corvin, Aiden; McQuillin, Andrew; Choudhury, Khalid; Datta, Susmita; Pimm, Jonathan; Thirumalai, Srinivasa; Puri, Vinay; Krasucki, Robert; Lawrence, Jacob; Quested, Digby; Bass, Nicholas; Gurling, Hugh; Crombie, Caroline; Fraser, Gillian; Kuan, Soh Leh; Walker, Nicholas; St Clair, David; Blackwood, Douglas H. R.; Muir, Walter J.; McGhee, Kevin A.; Pickard, Ben; Malloy, Pat; Maclean, Alan W.; van Beck, Margaret; Wray, Naomi R.; Macgregor, Stuart; Visscher, Peter M.; Pato, Michele T.; Medeiros, Helena; Middleton, Frank; Carvalho, Celia; Morley, Christopher; Fanous, Ayman; Conti, David; Knowles, James A.; Ferreira, Carlos Paz; Macedo, Antonio; Azevedo, M. Helena; Pato, Carlos N.; Stone, Jennifer L.; Ruderfer, Douglas M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Purcell, Shaun M.; Sklar, Pamela; Chambert, Kimberly; Kuruvilla, Finny; Gabriel, Stacey B.; Ardlie, Kristin; Moran, Jennifer L.; Scolnick, Edward M.

    2011-01-01

    We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed

  16. Multiple comparison procedures for neuroimaging genomewide association studies.

    Science.gov (United States)

    Hua, Wen-Yu; Nichols, Thomas E; Ghosh, Debashis

    2015-01-01

    Recent research in neuroimaging has focused on assessing associations between genetic variants that are measured on a genomewide scale and brain imaging phenotypes. A large number of works in the area apply massively univariate analyses on a genomewide basis to find single nucleotide polymorphisms that influence brain structure. In this paper, we propose using various dimensionality reduction methods on both brain structural MRI scans and genomic data, motivated by the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We also consider a new multiple testing adjustment method and compare it with two existing false discovery rate (FDR) adjustment methods. The simulation results suggest an increase in power for the proposed method. The real-data analysis suggests that the proposed procedure is able to find associations between genetic variants and brain volume differences that offer potentially new biological insights. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Association between childhood trauma and accelerated telomere erosion in adulthood: A meta-analytic study.

    Science.gov (United States)

    Li, Zongchang; He, Ying; Wang, Dong; Tang, Jingsong; Chen, Xiaogang

    2017-10-01

    Childhood trauma has long-term sequelae on health status and contributes to numbers of somatic and mental disorders in later life. Findings from experimental studies in animals suggest that telomere erosion may be a mediator of this relationship. However, results from human studies are heterogeneous. To address these inconsistencies, we performed a meta-analysis regarding the association between childhood trauma and telomere length in adulthood. Articles were identified by systematically searching the Medline, EMBASE and Web of Science databases. Twenty four studies, which include twenty six sample sets and 30,919 participants, met the inclusion criteria for meta-analyses. This meta-analyses revealed that individuals experienced childhood trauma have accelerated telomere erosion in adulthood, with a small effect size (r = -0.05, 95% CI = -0.08-0.03, p childhood trauma revealed a trend in difference between groups (Q = 5.24, p = 0.07). Analyses for individual trauma types revealed a significant association between childhood separation and telomere erosion (r = -0.09, p childhood trauma and accelerated telomere erosion in adulthood, and further revealed that different trauma types have various impacts on telomere. Additional research on the mechanism that links the individual types of childhood trauma with telomere is needed in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. New insights into survival trend analyses in cancer population-based studies: the SUDCAN methodology.

    Science.gov (United States)

    Uhry, Zoé; Bossard, Nadine; Remontet, Laurent; Iwaz, Jean; Roche, Laurent

    2017-01-01

    The main objective of the SUDCAN study was to compare, for 15 cancer sites, the trends in net survival and excess mortality rates from cancer 5 years after diagnosis between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland). The data were extracted from the EUROCARE-5 database. The study period ranged from 6 (Portugal, 2000-2005) to 18 years (Switzerland, 1989-2007). Trend analyses were carried out separately for each country and cancer site; the number of cases ranged from 1500 to 104 000 cases. We developed an original flexible excess rate modelling strategy that accounts for the continuous effects of age, year of diagnosis, time since diagnosis and their interactions. Nineteen models were constructed; they differed in the modelling of the effect of the year of diagnosis in terms of linearity, proportionality and interaction with age. The final model was chosen according to the Akaike Information Criterion. The fit was assessed graphically by comparing model estimates versus nonparametric (Pohar-Perme) net survival estimates. Out of the 90 analyses carried out, the effect of the year of diagnosis on the excess mortality rate depended on age in 61 and was nonproportional in 64; it was nonlinear in 27 out of the 75 analyses where this effect was considered. The model fit was overall satisfactory. We analysed successfully 15 cancer sites in six countries. The refined methodology proved necessary for detailed trend analyses. It is hoped that three-dimensional parametric modelling will be used more widely in net survival trend studies as it has major advantages over stratified analyses.

  19. Lack of association between PKLR rs3020781 and NOS1AP rs7538490 and type 2 diabetes, overweight, obesity and related metabolic phenotypes in a Danish large-scale study: case-control studies and analyses of quantitative traits

    Directory of Open Access Journals (Sweden)

    Almind Katrine

    2008-12-01

    Full Text Available Abstract Background Several studies in multiple ethnicities have reported linkage to type 2 diabetes on chromosome 1q21-25. Both PKLR encoding the liver pyruvate kinase and NOS1AP encoding the nitric oxide synthase 1 (neuronal adaptor protein (CAPON are positioned within this chromosomal region and are thus positional candidates for the observed linkage peak. The C-allele of PKLR rs3020781 and the T-allele of NOS1AP rs7538490 are reported to strongly associate with type 2 diabetes in various European-descent populations comprising a total of 2,198 individuals with a combined odds ratio (OR of 1.33 [1.16–1.54] and 1.53 [1.28–1.81], respectively. Our aim was to validate these findings by investigating the impact of the two variants on type 2 diabetes and related quantitative metabolic phenotypes in a large study sample of Danes. Further, we intended to expand the analyses by examining the effect of the variants in relation to overweight and obesity. Methods PKLR rs3020781 and NOS1AP rs7538490 were genotyped, using TaqMan allelic discrimination, in a combined study sample comprising a total of 16,801 and 16,913 individuals, respectively. The participants were ascertained from four different study groups; the population-based Inter99 cohort (nPKLR = 5,962, nNOS1AP = 6,008, a type 2 diabetic patient group (nPKLR = 1,873, nNOS1AP = 1,874 from Steno Diabetes Center, a population-based study sample (nPKLR = 599, nNOS1AP = 596 from Steno Diabetes Center and the ADDITION Denmark screening study cohort (nPKLR = 8,367, nNOS1AP = 8,435. Results In case-control studies we evaluated the potential association between rs3020781 and rs7538490 and type 2 diabetes and obesity. No significant associations were observed for type 2 diabetes (rs3020781: pAF = 0.49, OR = 1.02 [0.96–1.10]; rs7538490: pAF = 0.84, OR = 0.99 [0.93–1.06]. Neither did we show association with overweight or obesity. Additionally, the PKLR and the NOS1AP genotypes were demonstrated not

  20. Association between adolescent marriage and intimate partner violence: a study of young adult women in Bangladesh.

    Science.gov (United States)

    Rahman, Mosfequr; Hoque, Md Aminul; Mostofa, Md Golam; Makinoda, Satoru

    2014-03-01

    This study explores the association between adolescent marriage and intimate partner violence (IPV) among young adult women using 2007 Bangladesh Demographic Health Survey data. The analyses are restricted to young women 20 to 24 years old. Logistic regression analyses are constructed to estimate the odds ratios and 95% confidence intervals for the association between adolescent marriage and IPV in the past year. show that there is a strong significant relationship between adolescent marriage and experience of physical IPV in the past year among this population. Association between sexual IPV and adolescent marriage is insignificant. Adolescent marriage puts women at increased risk of physical IPV into their young adult period. Government agencies need to enforce existing law on the minimum age at marriage to reduce IPV among adolescent and young adult girls.

  1. Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder.

    Directory of Open Access Journals (Sweden)

    Fernando Navarro-Mateu

    Full Text Available OBJECTIVE: To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases. METHODS DATA SOURCES: Potential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK, PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network up until December 2011. STUDY SELECTION: Published observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review. DATA EXTRACTION: Two reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol. STATISTICAL ANALYSIS: A biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L' and the recessive model (SS/L+ and S'S'/L'+, was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I(2 index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed. RESULTS: 13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias. CONCLUSIONS: Current evidence does not support a direct effect of 5-HTTLPR

  2. Tritium sample analyses in the Savannah River and associated waterways following the K-reactor release of December 1991

    International Nuclear Information System (INIS)

    Beals, D.M.; Dunn, D.L.; Hall, G.; Kantelo, M.V.

    1992-01-01

    An unplanned release of tritiated water occurred at K reactor on SRS between 22-December and 25-December 1991. This water moved down through the effluent canal, Pen Branch, Steel Creek and finally to the Savannah River. Samples were collected in the Savannah River and associated waterways over a period of a month. The Environmental Technology Section (ETS) of the Savannah River Laboratory performed liquid scintillation analyses to monitor the passage of the tritiated water from SRS to the Atlantic Ocean

  3. Night shift work and breast cancer risk: what do the meta-analyses tell us?

    Science.gov (United States)

    Pahwa, Manisha; Labrèche, France; Demers, Paul A

    2018-05-22

    Objectives This paper aims to compare results, assess the quality, and discuss the implications of recently published meta-analyses of night shift work and breast cancer risk. Methods A comprehensive search was conducted for meta-analyses published from 2007-2017 that included at least one pooled effect size (ES) for breast cancer associated with any night shift work exposure metric and were accompanied by a systematic literature review. Pooled ES from each meta-analysis were ascertained with a focus on ever/never exposure associations. Assessments of heterogeneity and publication bias were also extracted. The AMSTAR 2 checklist was used to evaluate quality. Results Seven meta-analyses, published from 2013-2016, collectively included 30 cohort and case-control studies spanning 1996-2016. Five meta-analyses reported pooled ES for ever/never night shift work exposure; these ranged from 0.99 [95% confidence interval (CI) 0.95-1.03, N=10 cohort studies) to 1.40 (95% CI 1.13-1.73, N=9 high quality studies). Estimates for duration, frequency, and cumulative night shift work exposure were scant and mostly not statistically significant. Meta-analyses of cohort, Asian, and more fully-adjusted studies generally resulted in lower pooled ES than case-control, European, American, or minimally-adjusted studies. Most reported statistically significant between-study heterogeneity. Publication bias was not evident in any of the meta-analyses. Only one meta-analysis was strong in critical quality domains. Conclusions Fairly consistent elevated pooled ES were found for ever/never night shift work and breast cancer risk, but results for other shift work exposure metrics were inconclusive. Future evaluations of shift work should incorporate high quality meta-analyses that better appraise individual study quality.

  4. Sensitivity Study of Poisson's Ratio Used in Soil Structure Interaction (SSI) Analyses

    International Nuclear Information System (INIS)

    Han, Seung-ju; You, Dong-Hyun; Jang, Jung-bum; Yun, Kwan-hee

    2016-01-01

    The preliminary review for Design Certification (DC) of APR1400 was accepted by NRC on March 4, 2015. After the acceptance of the application for standard DC of APR1400, KHNP has responded the Request for Additional Information (RAI) raised by NRC to undertake a full design certification review. Design certification is achieved through the NRC's rulemaking process, and is founded on the staff's review of the application, which addresses the various safety issues associated with the proposed nuclear power plant design, independent of a specific site. The USNRC issued RAIs pertain to Design Control Document (DCD) Ch.3.7 'Seismic Design' is DCD Tables 3.7A-1 and 3.7A-2 show Poisson’s ratios in the S1 and S2 soil profiles used for SSI analysis as great as 0.47 and 0.48 respectively. Based on staff experience, use of Poisson's ratio approaching these values may result in numerical instability of the SSI analysis results. Sensitivity study is performed using the ACS SASSI NI model of APR1400 with S1 and S2 soil profiles to demonstrate that the Poisson’s ratio values used in the SSI analyses of S1 and S2 soil profile cases do not produce numerical instabilities in the SSI analysis results. No abrupt changes or spurious peaks, which tend to indicate existence of numerical sensitivities in the SASSI solutions, appear in the computed transfer functions of the original SSI analyses that have the maximum dynamic Poisson’s ratio values of 0.47 and 0.48 as well as in the re-computed transfer functions that have the maximum dynamic Poisson’s ratio values limited to 0.42 and 0.45

  5. Associations between male infertility and ancestry in South Americans: a case control study.

    Science.gov (United States)

    Skowronek, Maria Fernanda; Velazquez, Tatiana; Mut, Patricia; Figueiro, Gonzalo; Sans, Monica; Bertoni, Bernardo; Sapiro, Rossana

    2017-07-26

    Infertility affects 15% of human couples, with men being responsible in approximately 50% of cases. Moreover, the aetiology of male factor infertility is poorly understood. The majority of male factor infertility remains idiopathic and potentially genetic in origin. The association of the Y chromosome and mitochondrial haplogroups with male infertility has been previously reported. This association differs between studied populations and their geographical distributions. These effects have been only rarely analysed in mixed populations, such as South Americans. In this study, we analysed the contributions of the Y chromosome and mitochondrial haplogroups to male infertility in a mixed population. A case control study was conducted. Regular PCR and high-resolutionmelting- real-time PCR were performed to type haplogroups from fertile and infertile men. The sperm parameters from infertile men were compared in each haplogroup by logistic regression analysis and ANOVA. The genotyping confirmed the known admixture characteristic of the Uruguayan population. The European paternal contribution was higher than the maternal contribution in both fertile and infertile men. Neither maternal nor paternal ancestry presented differences between the cases and controls. Men belonging to the Y chromosome haplogroup F(xK) more frequently presented with an abnormal sperm morphology than men from other haplogroups. The sperm parameters were not associated with the mitochondrial haplogroups. The data presented in this study showed an association between male infertility and ancestry in the Uruguayan population. Specifically, abnormal sperm morphology was associated with the Y chromosome haplogroup F(xK). Since the Y chromosome lacks recombination, these data suggest that some genes that determine sperm morphology might be inherited in blocks with the region that determines specific haplogroups. However, the possible association between the Y chromosome haplogroup F(xK) and sperm

  6. YY1 binding association with sex-biased transcription revealed through X-linked transcript levels and allelic binding analyses.

    Science.gov (United States)

    Chen, Chih-Yu; Shi, Wenqiang; Balaton, Bradley P; Matthews, Allison M; Li, Yifeng; Arenillas, David J; Mathelier, Anthony; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Brown, Carolyn J; Wasserman, Wyeth W

    2016-11-18

    Sex differences in susceptibility and progression have been reported in numerous diseases. Female cells have two copies of the X chromosome with X-chromosome inactivation imparting mono-allelic gene silencing for dosage compensation. However, a subset of genes, named escapees, escape silencing and are transcribed bi-allelically resulting in sexual dimorphism. Here we conducted in silico analyses of the sexes using human datasets to gain perspectives into such regulation. We identified transcription start sites of escapees (escTSSs) based on higher transcription levels in female cells using FANTOM5 CAGE data. Significant over-representations of YY1 transcription factor binding motif and ChIP-seq peaks around escTSSs highlighted its positive association with escapees. Furthermore, YY1 occupancy is significantly biased towards the inactive X (Xi) at long non-coding RNA loci that are frequent contacts of Xi-specific superloops. Our study suggests a role for YY1 in transcriptional activity on Xi in general through sequence-specific binding, and its involvement at superloop anchors.

  7. Altered Brain Activity in Unipolar Depression Revisited: Meta-analyses of Neuroimaging Studies.

    Science.gov (United States)

    Müller, Veronika I; Cieslik, Edna C; Serbanescu, Ilinca; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

    2017-01-01

    major depressive disorder. For meta-analyses with a minimum of 17 experiments available, separate analyses were performed for increases and decreases. In total, 57 studies with 99 individual neuroimaging experiments comprising in total 1058 patients were included; 34 of them tested cognitive and 65 emotional processing. Overall analyses across cognitive processing experiments (P > .29) and across emotional processing experiments (P > .47) revealed no significant results. Similarly, no convergence was found in analyses investigating positive (all P > .15), negative (all P > .76), or memory (all P > .48) processes. Analyses that restricted inclusion of confounds (eg, medication, comorbidity, age) did not change the results. Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual experiments, these inconsistencies may relate to use of uncorrected inference procedures, differences in experimental design and contrasts, or heterogeneous clinical populations; meta-analytically, differences may be attributable to varying inclusion and exclusion criteria or rather liberal statistical inference approaches.

  8. The association between pulse wave velocity and cognitive function: the Sydney Memory and Ageing Study.

    Science.gov (United States)

    Singer, Joel; Trollor, Julian N; Crawford, John; O'Rourke, Michael F; Baune, Bernhard T; Brodaty, Henry; Samaras, Katherine; Kochan, Nicole A; Campbell, Lesley; Sachdev, Perminder S; Smith, Evelyn

    2013-01-01

    Pulse wave velocity (PWV) is a measure of arterial stiffness and its increase with ageing has been associated with damage to cerebral microvessels and cognitive impairment. This study examined the relationship between carotid-femoral PWV and specific domains of cognitive function in a non-demented elderly sample. Data were drawn from the Sydney Memory and Ageing Study, a cohort study of non-demented community-dwelling individuals aged 70-90 years, assessed in successive waves two years apart. In Wave 2, PWV and cognitive function were measured in 319 participants. Linear regression was used to analyse the cross-sectional relationship between arterial stiffness and cognitive function in the whole sample, and separately for men and women. Analysis of covariance was used to assess potential differences in cognition between subjects with PWV measurements in the top and bottom tertiles of the cohort. Covariates were age, education, body mass index, pulse rate, systolic blood pressure, cholesterol, depression, alcohol, smoking, hormone replacement therapy, apolipoprotein E ε4 genotype, use of anti-hypertensive medications, history of stroke, transient ischemic attack, myocardial infarction, angina, diabetes, and also sex for the whole sample analyses. There was no association between PWV and cognition after Bonferroni correction for multiple testing. When examining this association for males and females separately, an association was found in males, with higher PWV being associated with lower global cognition and memory, however, a significant difference between PWV and cognition between males and females was not found. A higher level of PWV was not associated with lower cognitive function in the whole sample.

  9. Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder.

    Science.gov (United States)

    Navarro-Mateu, Fernando; Escámez, Teresa; Koenen, Karestan C; Alonso, Jordi; Sánchez-Meca, Julio

    2013-01-01

    To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases. Potential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011. Published observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review. Two reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol. A biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L') and the recessive model (SS/L+ and S'S'/L'+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I(2) index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed. 13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias. Current evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples

  10. Meta-Analyses of Association Between BRAFV600E Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Qing Zhang

    2016-02-01

    Full Text Available Background/Aims: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. Methods: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs were calculated to assess the relationship between clinicopathological features and BRAFV600E mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. Results: Of 25,241 cases with PTC, 15,290 (60.6% were positive for BRAF mutation and 9,951 (39.4% were tested negative for BRAF mutation. Negative status of BRAFV600E mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97 and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64. By contrast, positive status of BRAFV600E mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32, extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63, TNM stage (OR = 1.67; 95%CI = 1.53-1.81, lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93, vascular invasion (OR = 1.47; 95%CI = 1.22-1.79 and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18. However, there was no significant association between BRAFV600E mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07, tumor size (OR = 0.84; 95%CI = 0.64-1.09 and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27. Conclusion: This meta-analysis confirmed significant associations between BRAFV600E mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence

  11. Methodological Quality Assessment of Meta-analyses in Endodontics.

    Science.gov (United States)

    Kattan, Sereen; Lee, Su-Min; Kohli, Meetu R; Setzer, Frank C; Karabucak, Bekir

    2018-01-01

    The objectives of this review were to assess the methodological quality of published meta-analyses related to endodontics using the assessment of multiple systematic reviews (AMSTAR) tool and to provide a follow-up to previously published reviews. Three electronic databases were searched for eligible studies according to the inclusion and exclusion criteria: Embase via Ovid, The Cochrane Library, and Scopus. The electronic search was amended by a hand search of 6 dental journals (International Endodontic Journal; Journal of Endodontics; Australian Endodontic Journal; Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology; Endodontics and Dental Traumatology; and Journal of Dental Research). The searches were conducted to include articles published after July 2009, and the deadline for inclusion of the meta-analyses was November 30, 2016. The AMSTAR assessment tool was used to evaluate the methodological quality of all included studies. A total of 36 reports of meta-analyses were included. The overall quality of the meta-analyses reports was found to be medium, with an estimated mean overall AMSTAR score of 7.25 (95% confidence interval, 6.59-7.90). The most poorly assessed areas were providing an a priori design, the assessment of the status of publication, and publication bias. In recent publications in the field of endodontics, the overall quality of the reported meta-analyses is medium according to AMSTAR. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Genome-Wide Association Analyses Highlight the Potential for Different Genetic Mechanisms for Litter Size Among Sheep Breeds

    Science.gov (United States)

    Xu, Song-Song; Gao, Lei; Xie, Xing-Long; Ren, Yan-Ling; Shen, Zhi-Qiang; Wang, Feng; Shen, Min; Eyϸórsdóttir, Emma; Hallsson, Jón H.; Kiseleva, Tatyana; Kantanen, Juha; Li, Meng-Hua

    2018-01-01

    Reproduction is an important trait in sheep breeding as well as in other livestock. However, despite its importance the genetic mechanisms of litter size in domestic sheep (Ovis aries) are still poorly understood. To explore genetic mechanisms underlying the variation in litter size, we conducted multiple independent genome-wide association studies in five sheep breeds of high prolificacy (Wadi, Hu, Icelandic, Finnsheep, and Romanov) and one low prolificacy (Texel) using the Ovine Infinium HD BeadChip, respectively. We identified different sets of candidate genes associated with litter size in different breeds: BMPR1B, FBN1, and MMP2 in Wadi; GRIA2, SMAD1, and CTNNB1 in Hu; NCOA1 in Icelandic; INHBB, NF1, FLT1, PTGS2, and PLCB3 in Finnsheep; ESR2 in Romanov and ESR1, GHR, ETS1, MMP15, FLI1, and SPP1 in Texel. Further annotation of genes and bioinformatics analyses revealed that different biological pathways could be involved in the variation in litter size of females: hormone secretion (FSH and LH) in Wadi and Hu, placenta and embryonic lethality in Icelandic, folliculogenesis and LH signaling in Finnsheep, ovulation and preovulatory follicle maturation in Romanov, and estrogen and follicular growth in Texel. Taken together, our results provide new insights into the genetic mechanisms underlying the prolificacy trait in sheep and other mammals, suggesting targets for selection where the aim is to increase prolificacy in breeding projects.

  13. The interrelation between hypothyroidism and glaucoma: a critical review and meta-analyses.

    Science.gov (United States)

    Thvilum, Marianne; Brandt, Frans; Brix, Thomas Heiberg; Hegedüs, Laszlo

    2017-12-01

    Data on the association between hypothyroidism and glaucoma are conflicting. We sought to shed light on this by conducting a critical review and meta-analyses. The meta-analyses were conducted in adherence with the widely accepted MOOSE guidelines. Using the Medical Subject Heading (MeSH) terms: hypothyroidism, myxoedema and glaucoma or intraocular pressure, case-control studies, cohort studies and cross-sectional studies were identified (PubMed) and reviewed. Using meta-analysis, the relative risk (RR) of coexistence of glaucoma and hypothyroidism was calculated. Based on the literature search, thirteen studies fulfilled the inclusion criteria and could be categorized into two groups based on the exposure. The designs of the studies varied considerably, and there was heterogeneity related to lack of power, weak phenotype classifications and length of follow-up. Eight studies had glaucoma (5757 patients) as exposure and hypothyroidism as outcome. Among these, we found a non-significantly increased risk of hypothyroidism associated with glaucoma (RR 1.65; 95% confidence interval [CI]: 0.97-2.82). Based on five studies (168 006 patients) with hypothyroidism as exposure and glaucoma as outcome, we found the risk of glaucoma to be significantly increased (RR 1.33; 95% CI: 1.13-1.58). Based on these meta-analyses, there seems to be an association between hypothyroidism and glaucoma, which does not seem to be the case between glaucoma and hypothyroidism. However, larger scale studies with better phenotype classification, longer follow-up and taking comorbidity and other biases into consideration are needed to address a potential causal relationship. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  14. The association between intelligence and telomere length: a longitudinal population based study.

    Directory of Open Access Journals (Sweden)

    Eva M Kingma

    Full Text Available Low intelligence has been associated with poor health and mortality, but underlying mechanisms remain obscure. We hypothesized that low intelligence is associated with accelerated biological ageing as reflected by telomere length; we suggested potential mediation of this association by unhealthy behaviors and low socioeconomic position. The study was performed in a longitudinal population-based cohort study of 895 participants (46.8% males. Intelligence was measured with the Generalized Aptitude-Test Battery at mean age 52.8 years (33-79 years, SD=11.3. Leukocyte telomere length was measured by PCR. Lifestyle and socioeconomic factors were assessed using written self-report measures. Linear regression analyses, adjusted for age, sex, and telomere length measured at the first assessment wave (T1, showed that low intelligence was associated with shorter leukocyte telomere length at approximately 2 years follow-up (beta= .081, t=2.160, p= .031. Nearly 40% of this association was explained by an unhealthy lifestyle, while low socioeconomic position did not add any significant mediation. Low intelligence may be a risk factor for accelerated biological ageing, thereby providing an explanation for its association with poor health and mortality.

  15. Systematic review and meta-analyses

    DEFF Research Database (Denmark)

    Dreier, Julie Werenberg; Andersen, Anne-Marie Nybo; Berg-Beckhoff, Gabriele

    2014-01-01

    1990 were excluded. RESULTS: The available literature supported an increased risk of adverse offspring health in association with fever during pregnancy. The strongest evidence was available for neural tube defects, congenital heart defects, and oral clefts, in which meta-analyses suggested between a 1...

  16. Phylogenetic study on Shiraia bambusicola by rDNA sequence analyses.

    Science.gov (United States)

    Cheng, Tian-Fan; Jia, Xiao-Ming; Ma, Xiao-Hang; Lin, Hai-Ping; Zhao, Yu-Hua

    2004-01-01

    In this study, 18S rDNA and ITS-5.8S rDNA regions of four Shiraia bambusicola isolates collected from different species of bamboos were amplified by PCR with universal primer pairs NS1/NS8 and ITS5/ITS4, respectively, and sequenced. Phylogenetic analyses were conducted on three selected datasets of rDNA sequences. Maximum parsimony, distance and maximum likelihood criteria were used to infer trees. Morphological characteristics were also observed. The positioning of Shiraia in the order Pleosporales was well supported by bootstrap, which agreed with the placement by Amano (1980) according to their morphology. We did not find significant inter-hostal differences among these four isolates from different species of bamboos. From the results of analyses and comparison of their rDNA sequences, we conclude that Shiraia should be classified into Pleosporales as Amano (1980) proposed and suggest that it might be positioned in the family Phaeosphaeriaceae. Copyright 2004 WILEY-VCH Verlag GmbH & Co.

  17. Smokers' increased risk for disability pension: social confounding or health-mediated effects? Gender-specific analyses of the Hordaland Health Study cohort.

    Science.gov (United States)

    Haukenes, Inger; Riise, Trond; Haug, Kjell; Farbu, Erlend; Maeland, John Gunnar

    2013-09-01

    Studies indicate that cigarette smokers have an increased risk for disability pension, presumably mediated by adverse health effects. However, smoking is also related to socioeconomic status. The current study examined the association between smoking and subsequent disability pension, and whether the association is explained by social confounding and/or health-related mediation. A subsample of 7934 men and 8488 women, aged 40-46, from the Hordaland Health Study, Norway (1997-1999), provided baseline information on smoking status, self-reported health measures and socioeconomic status. Outcome was register-based disability pension from 12 months after baseline to end of 2004. Gender stratified Cox regression analyses were used adjusted for socioeconomic status, physical activity, self-reported health and musculoskeletal pain sites. A total of 155 (2%) men and 333 (3.9%) women were granted disability pension during follow-up. The unadjusted disability risk associated with heavy smoking versus non-smoking was 1.88 (95% CI 1.23 to 2.89) among men and 3.06 (95% CI 2.23 to 4.20) among women. In multivariate analyses, adjusting for socioeconomic status, HRs were 1.33 (95% CI 0.84 to 2.11) among men and 2.22 (95% CI 1.58 to 3.13) among women. Final adjustment for physical activity, self-reported health and musculoskeletal pain further reduced the effect of heavy smoking in women (HR=1.53, 95% CI 1.09 to 2.16). Socioeconomic status confounded the smoking-related risk for disability pension; for female heavy smokers, however, a significant increased risk persisted after adjustment. Women may be particularly vulnerable to heavy smoking and to its sociomedical consequences, such as disability pension.

  18. The Association between Meditation Practice and Job Performance: A Cross-Sectional Study.

    Science.gov (United States)

    Shiba, Koichiro; Nishimoto, Masahiro; Sugimoto, Minami; Ishikawa, Yoshiki

    2015-01-01

    Many previous studies have shown that meditation practice has a positive impact on cognitive and non-cognitive functioning, which are related to job performance. Thus, the aims of this study were to (1) estimate the prevalence of meditation practice, (2) identify the characteristics of individuals who practice meditation, and (3) examine the association between meditation practice and job performance. Two population-based, cross-sectional surveys were conducted. In study 1, we examined the prevalence of meditation practice and the characteristics of the persons practicing meditation; in Study 2, we examined the association between meditation practice and job performance. The outcome variables included work engagement, subjective job performance, and job satisfaction. The Utrecht Work Engagement Scale was used to assess work engagement, the World Health Organization Health and Work Performance Questionnaire (HPQ) was used to measure subjective job performance, and a scale developed by the Japanese government was used to assess job satisfaction. Hierarchical multiple regression analyses were used in Study 2. Demographic characteristics and behavioral risk factors were included as covariates in the analyses. The results of Study 1 indicated that 3.9% of persons surveyed (n = 30,665) practiced meditation; these individuals were younger and had a higher education, higher household income, higher stress level, and lower body mass index than those who did not practice meditation. The results of Study 2 (n = 1,470) indicated that meditation practice was significantly predictive of work engagement (β = 0.112, p meditation practice may positively influence job performance, including job satisfaction, subjective job performance, and work engagement.

  19. Is quality and completeness of reporting of systematic reviews and meta-analyses published in high impact radiology journals associated with citation rates?

    Science.gov (United States)

    van der Pol, Christian B; McInnes, Matthew D F; Petrcich, William; Tunis, Adam S; Hanna, Ramez

    2015-01-01

    The purpose of this study is to determine whether study quality and completeness of reporting of systematic reviews (SR) and meta-analyses (MA) published in high impact factor (IF) radiology journals is associated with citation rates. All SR and MA published in English between Jan 2007-Dec 2011, in radiology journals with an IF >2.75, were identified on Ovid MEDLINE. The Assessing the Methodologic Quality of Systematic Reviews (AMSTAR) checklist for study quality, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for study completeness, was applied to each SR & MA. Each SR & MA was then searched in Google Scholar to yield a citation rate. Spearman correlation coefficients were used to assess the relationship between AMSTAR and PRISMA results with citation rate. Multivariate analyses were performed to account for the effect of journal IF and journal 5-year IF on correlation with citation rate. Values were reported as medians with interquartile range (IQR) provided. 129 studies from 11 journals were included (50 SR and 79 MA). Median AMSTAR result was 8.0/11 (IQR: 5-9) and median PRISMA result was 23.0/27 (IQR: 21-25). The median citation rate for SR & MA was 0.73 citations/month post-publication (IQR: 0.40-1.17). There was a positive correlation between both AMSTAR and PRISMA results and SR & MA citation rate; ρ=0.323 (P=0.0002) and ρ=0.327 (P=0.0002) respectively. Positive correlation persisted for AMSTAR and PRISMA results after journal IF was partialed out; ρ=0.243 (P=0.006) and ρ=0.256 (P=0.004), and after journal 5-year IF was partialed out; ρ=0.235 (P=0.008) and ρ=0.243 (P=0.006) respectively. There is a positive correlation between the quality and the completeness of a reported SR or MA with citation rate which persists when adjusted for journal IF and journal 5-year IF.

  20. Sniffing out significant "Pee values": genome wide association study of asparagus anosmia.

    Science.gov (United States)

    Markt, Sarah C; Nuttall, Elizabeth; Turman, Constance; Sinnott, Jennifer; Rimm, Eric B; Ecsedy, Ethan; Unger, Robert H; Fall, Katja; Finn, Stephen; Jensen, Majken K; Rider, Jennifer R; Kraft, Peter; Mucci, Lorelei A

    2016-12-13

     To determine the inherited factors associated with the ability to smell asparagus metabolites in urine.  Genome wide association study.  Nurses' Health Study and Health Professionals Follow-up Study cohorts.  6909 men and women of European-American descent with available genetic data from genome wide association studies.  Participants were characterized as asparagus smellers if they strongly agreed with the prompt "after eating asparagus, you notice a strong characteristic odor in your urine," and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553.  A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Associations between VO2max and vitality in older workers: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    van der Beek Allard J

    2010-11-01

    Full Text Available Abstract Background To prevent early exit from work, it is important to study which factors contribute to healthy ageing. One concept that is assumed to be closely related to, and therefore may influence healthy ageing, is vitality. Vitality consists of both a mental and a physical component, and is characterised by a perceived high energy level, decreased feelings of fatigue, and feeling fit. Since VO2max gives an indication of one's aerobic fitness, which can be improved by increased levels of physical activity, and because feeling fit is one of the main characteristics of vitality, it is hypothesised that VO2max is related to vitality. Therefore, the aim of this study was to investigate the associations between VO2max and vitality. Methods In 427 older workers (aged 45 + years participating in the Vital@Work study, VO2max was estimated at baseline using the 2-km UKK walk test. Vitality was measured by both the UWES Vitality Scale and the RAND-36 Vitality Scale. Associations were analysed using linear regression analyses. Results The linear regression models, adjusted for age, showed a significant association between VO2max and vitality measured with the RAND-36 Vitality Scale (β = 0.446; 95% CI: 0.220-0.673. There was no significant association between VO2max and vitality measured with the UWES (β = -0.006; 95% CI:-0.017 - 0.006, after adjusting for age, gender and chronic disease status. Conclusions VO2max was associated with a general measure of vitality (measured with the RAND-36 Vitality Scale, but not with occupational health related vitality (measured with the UWES Vitality Scale. The idea that physical exercise can be used as an effective tool for improving vitality was supported in this study. Trial registration NTR1240

  2. Associations between VO2max and vitality in older workers: a cross-sectional study.

    Science.gov (United States)

    Strijk, Jorien E; Proper, Karin I; Klaver, Linda; van der Beek, Allard J; van Mechelen, Willem

    2010-11-09

    To prevent early exit from work, it is important to study which factors contribute to healthy ageing. One concept that is assumed to be closely related to, and therefore may influence healthy ageing, is vitality. Vitality consists of both a mental and a physical component, and is characterised by a perceived high energy level, decreased feelings of fatigue, and feeling fit. Since VO2max gives an indication of one's aerobic fitness, which can be improved by increased levels of physical activity, and because feeling fit is one of the main characteristics of vitality, it is hypothesised that VO2max is related to vitality. Therefore, the aim of this study was to investigate the associations between VO2max and vitality. In 427 older workers (aged 45 + years) participating in the Vital@Work study, VO2max was estimated at baseline using the 2-km UKK walk test. Vitality was measured by both the UWES Vitality Scale and the RAND-36 Vitality Scale. Associations were analysed using linear regression analyses. The linear regression models, adjusted for age, showed a significant association between VO2max and vitality measured with the RAND-36 Vitality Scale (β = 0.446; 95% CI: 0.220-0.673). There was no significant association between VO2max and vitality measured with the UWES (β = -0.006; 95% CI:-0.017 - 0.006), after adjusting for age, gender and chronic disease status. VO2max was associated with a general measure of vitality (measured with the RAND-36 Vitality Scale), but not with occupational health related vitality (measured with the UWES Vitality Scale). The idea that physical exercise can be used as an effective tool for improving vitality was supported in this study. NTR1240.

  3. Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study

    Directory of Open Access Journals (Sweden)

    Venojärvi Mika

    2011-01-01

    Full Text Available Abstract Background Adiponectin, secreted mainly by mature adipocytes, is a protein with insulin-sensitising and anti-atherogenic effects. Human adiponectin is encoded by the ADIPOQ gene on the chromosomal locus 3q27. Variations in ADIPOQ are associated with obesity, type 2 diabetes (T2DM and related phenotypes in several populations. Our aim was to study the association of the ADIPOQ variations with body weight, serum adiponectin concentrations and conversion to T2DM in overweight subjects with impaired glucose tolerance. Moreover, we investigated whether ADIPOQ gene variants modify the effect of lifestyle changes on these traits. Methods Participants in the Finnish Diabetes Prevention Study were randomly assigned to a lifestyle intervention group or a control group. Those whose DNA was available (n = 507 were genotyped for ten ADIPOQ single nucleotide polymorphisms (SNPs. Associations between SNPs and baseline body weight and serum adiponectin concentrations were analysed using the univariate analysis of variance. The 4-year longitudinal weight data were analysed using linear mixed models analysis and the change in serum adiponectin from baseline to year four was analysed using Kruskal-Wallis test. In addition, the association of SNPs with the risk of developing T2DM during the follow-up of 0-11 (mean 6.34 years was analysed by Cox regression analysis. Results rs266729, rs16861205, rs1501299, rs3821799 and rs6773957 associated significantly (p Conclusions These results from the Finnish Diabetes Prevention Study support the concept that genetic variation in ADIPOQ locus contributes to variation in body size and serum adiponectin concentrations and may also modify the risk of developing T2DM. Trial registration number ClinicalTrials.gov NCT00518167

  4. Associations between strain in domestic work and self-rated health: a study of employed women in Sweden.

    Science.gov (United States)

    Staland-Nyman, Carin; Alexanderson, Kristina; Hensing, Gunnel

    2008-01-01

    The aim of this study was to analyse the association between strain in domestic work and self-rated health among employed women in Sweden, using two different methods of measuring strain in domestic work. Questionnaire data were collected on health and living conditions in paid and unpaid work for employed women (n=1,417), aged 17-64 years. "Domestic job strain'' was an application of the demand-control model developed by Karasek and Theorell, and "Domestic work equity and marital satisfaction'' was measured by questions on the division of and responsibility for domestic work and relationship with spouse/cohabiter. Self-rated health was measured using the SF-36 Health Survey. Associations were analysed by bivariate and multivariate linear regression analyses, and reported as standardized regression coefficients. Higher strain in domestic work was associated with lower self-rated health, also after controlling for potential confounders and according to both strain measures. "Domestic work equity and marital satisfaction'' showed for example negative associations with mental health beta -0.211 (p<0.001), vitality beta -0.195 (p<0.001), social function -0.132 (p<0.01) and physical role beta -0.115 (p<0.01). The highest associations between "Domestic job strain'' and SF-36 were found for vitality beta -0.156 (p<0.001), mental health beta -0.123 (p<0.001). Strain in domestic work, including perceived inequity in the relationship and lack of a satisfactory relationship with a spouse/cohabiter, was associated with lower self-rated health in this cross-sectional study. Future research needs to address the specific importance of strain in domestic work as a contributory factor to women's ill-health.

  5. Factors associated with survival of epiploic foramen entrapment colic: a multicentre, international study.

    Science.gov (United States)

    Archer, D C; Pinchbeck, G L; Proudman, C J

    2011-08-01

    Epiploic foramen entrapment (EFE) has been associated with reduced post operative survival compared to other types of colic but specific factors associated with reduced long-term survival of these cases have not been evaluated in a large number of horses using survival analysis. To describe post operative survival of EFE cases and to identify factors associated with long-term survival. A prospective, multicentre, international study was conducted using clinical data and long-term follow-up information for 126 horses diagnosed with EFE during exploratory laparotomy at 15 clinics in the UK, Ireland and USA. Descriptive data were generated and survival analysis performed to identify factors associated with reduced post operative survival. For the EFE cohort that recovered following anaesthesia, survival to hospital discharge was 78.5%. Survival to 1 and 2 years post operatively was 50.6 and 34.3%, respectively. The median survival time of EFE cases undergoing surgery was 397 days. Increased packed cell volume (PCV) and increased length of small intestine (SI) resected were significantly associated with increased likelihood of mortality when multivariable analysis of pre- and intraoperative variables were analysed. When all pre-, intra- and post operative variables were analysed separately, only horses that developed post operative ileus (POI) were shown to be at increased likelihood of mortality. Increased PCV, increased length of SI resected and POI are all associated with increased likelihood of mortality of EFE cases. This emphasises the importance of early diagnosis and treatment and the need for improved strategies in the management of POI in order to reduce post operative mortality in these cases. The present study provides evidence-based information to clinicians and owners of horses undergoing surgery for EFE about long-term survival. These results are applicable to university and large private clinics over a wide geographical area. © 2011 EVJ Ltd.

  6. Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis.

    Science.gov (United States)

    Alg, Varinder S; Ke, Xiayi; Grieve, Joan; Bonner, Stephen; Walsh, Daniel C; Bulters, Diederik; Kitchen, Neil; Houlden, Henry; Werring, David J

    2018-01-15

    Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls. We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured). We also undertook a meta-analysis of two previous studies examining this SNP. The rs243865 T allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33], p = .01) and in multi-variable analyses adjusted for smoking and hypertension status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p = .017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p = .11). Our study demonstrated an association between the functional MMP-2 rs243865 variant and IAs. Our findings suggest a genetic role for altered extracellular matrix integrity in the pathogenesis of IA development and rupture.

  7. The Hanford study: issues in analysing and interpreting data from occupational studies

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1987-01-01

    Updated analyses of workers at the Hanford Site provided no evidence of a correlation of radiation exposure and mortality from all cancers or mortality from leukemia. Potentially confounding factors were examined, and to the extent possible taken account of in these analyses. Risk estimates for leukemia and for all cancers except leukemia were calculated and compared with those from other sources. For leukemia, consideration was given to modifying factors such as age at exposure and time from exposure. (author)

  8. Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Mogensen, Mette S; Borch-Johnsen, Knut

    2008-01-01

    The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case-control stud......The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case......-control studies and analyses of obesity-related quantitative traits. Moreover, since environmental and genetic factors may modulate the impact of a genetic variant, we wanted to perform such interaction analyses. We focused on physical activity as an environmental risk factor, and on the GWA identified obesity...

  9. Mixed Approach Retrospective Analyses of Suicide and Suicidal Ideation for Brand Compared with Generic Central Nervous System Drugs.

    Science.gov (United States)

    Cheng, Ning; Rahman, Md Motiur; Alatawi, Yasser; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, C David; Hansen, Richard A

    2018-04-01

    Several different types of drugs acting on the central nervous system (CNS) have previously been associated with an increased risk of suicide and suicidal ideation (broadly referred to as suicide). However, a differential association between brand and generic CNS drugs and suicide has not been reported. This study compares suicide adverse event rates for brand versus generic CNS drugs using multiple sources of data. Selected examples of CNS drugs (sertraline, gabapentin, zolpidem, and methylphenidate) were evaluated via the US FDA Adverse Event Reporting System (FAERS) for a hypothesis-generating study, and then via administrative claims and electronic health record (EHR) data for a more rigorous retrospective cohort study. Disproportionality analyses with reporting odds ratios and 95% confidence intervals (CIs) were used in the FAERS analyses to quantify the association between each drug and reported suicide. For the cohort studies, Cox proportional hazards models were used, controlling for demographic and clinical characteristics as well as the background risk of suicide in the insured population. The FAERS analyses found significantly lower suicide reporting rates for brands compared with generics for all four studied products (Breslow-Day P brand CNS drugs in FAERS and adjusted retrospective cohort analyses remained significant only for sertraline. However, even for sertraline, temporal confounding related to the close proximity of black box warnings and generic availability is possible. Additional analyses in larger data sources with additional drugs are needed.

  10. Surrogacy of progression free survival for overall survival in metastatic breast cancer studies: Meta-analyses of published studies.

    Science.gov (United States)

    Kundu, Madan G; Acharyya, Suddhasatta

    2017-02-01

    PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR OS (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatment effects on PFS were determined using hazard ratio (HR PFS ), increase in median PFS (ΔMED PFS ) and % increase in median PFS (%ΔMED PFS ). Diagnostic accuracy of PFS measures (HR PFS , ΔMED PFS and %ΔMED PFS ) in predicting significant HR OS was assessed using receiver operating characteristic (ROC) curves and classification tree approach (CART). Seventy-four cases (i.e., treatment to control comparisons) from 65 individual publications were identified for the analyses. Of these, 16 cases reported significant treatment effect on HR OS at 5% level of significance. Median number of deaths reported in these cases were 153. Area under the ROC curve (AUC) for diagnostic measures as HR PFS , ΔMED PFS and %ΔMED PFS were 0.69, 0.70 and 0.75, respectively. Classification tree results identified %ΔMED PFS and number of deaths as diagnostic measure for significant HR OS . Only 7.9% (3/39) cases with ΔMED PFS shorter than 48.27% reported significant HR OS . There were 7 cases with ΔMED PFS of 48.27% or more and number of deaths reported as 227 or more - of these 5 cases reported significant HR OS . %ΔMED PFS was found to be a better diagnostic measure for predicting significant HR OS . Our analysis results also suggest that consideration of total number of deaths may further improve its diagnostic performance. Based on our study results, the studies with 50% improvement in median PFS are more likely to produce significant HR OS if the total number of OS events at the time of analysis is 227 or more. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Suicide assisted by right-to-die associations: a population based cohort study.

    Science.gov (United States)

    Steck, Nicole; Junker, Christoph; Maessen, Maud; Reisch, Thomas; Zwahlen, Marcel; Egger, Matthias

    2014-04-01

    In Switzerland, assisted suicide is legal but there is concern that vulnerable or disadvantaged groups are more likely to die in this way than other people. We examined socio-economic factors associated with assisted suicide. We linked the suicides assisted by right-to-die associations during 2003-08 to a census-based longitudinal study of the Swiss population. We used Cox and logistic regression models to examine associations with gender, age, marital status, education, religion, type of household, urbanization, neighbourhood socio-economic position and other variables. Separate analyses were done for younger (25 to 64 years) and older (65 to 94 years) people. Analyses were based on 5 004 403 Swiss residents and 1301 assisted suicides (439 in the younger and 862 in the older group). In 1093 (84.0%) assisted suicides, an underlying cause was recorded; cancer was the most common cause (508, 46.5%). In both age groups, assisted suicide was more likely in women than in men, those living alone compared with those living with others and in those with no religious affiliation compared with Protestants or Catholics. The rate was also higher in more educated people, in urban compared with rural areas and in neighbourhoods of higher socio-economic position. In older people, assisted suicide was more likely in the divorced compared with the married; in younger people, having children was associated with a lower rate. Assisted suicide in Switzerland was associated with female gender and situations that may indicate greater vulnerability such as living alone or being divorced, but also with higher education and higher socio-economic position.

  12. Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses

    Science.gov (United States)

    Takeuchi, H; Taki, Y; Hashizume, H; Asano, K; Asano, M; Sassa, Y; Yokota, S; Kotozaki, Y; Nouchi, R; Kawashima, R

    2016-01-01

    Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence. PMID:26728566

  13. Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses.

    Science.gov (United States)

    Takeuchi, H; Taki, Y; Hashizume, H; Asano, K; Asano, M; Sassa, Y; Yokota, S; Kotozaki, Y; Nouchi, R; Kawashima, R

    2016-12-01

    Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

  14. Sniffing out significant “Pee values”: genome wide association study of asparagus anosmia

    Science.gov (United States)

    Markt, Sarah C; Nuttall, Elizabeth; Turman, Constance; Sinnott, Jennifer; Rimm, Eric B; Ecsedy, Ethan; Unger, Robert H; Fall, Katja; Finn, Stephen; Jensen, Majken K; Rider, Jennifer R; Kraft, Peter

    2016-01-01

    Objective To determine the inherited factors associated with the ability to smell asparagus metabolites in urine. Design Genome wide association study. Setting Nurses’ Health Study and Health Professionals Follow-up Study cohorts. Participants 6909 men and women of European-American descent with available genetic data from genome wide association studies. Main outcome measure Participants were characterized as asparagus smellers if they strongly agreed with the prompt “after eating asparagus, you notice a strong characteristic odor in your urine,” and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553. Conclusion A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing. PMID:27965198

  15. Genome-wide meta-analyses identify multiple loci associated with smoking behavior

    NARCIS (Netherlands)

    H. Furberg (Helena); Y. Kim (Yunjung); J. Dackor (Jennifer); E.A. Boerwinkle (Eric); N. Franceschini (Nora); D. Ardissino (Diego); L. Bernardinelli (Luisa); P.M. Mannucci (Pier); F. Mauri (Francesco); P.A. Merlini (Piera); D. Absher (Devin); T.L. Assimes (Themistocles); S.P. Fortmann (Stephen); C. Iribarren (Carlos); J.W. Knowles (Joshua); T. Quertermous (Thomas); L. Ferrucci (Luigi); T. Tanaka (Toshiko); J.C. Bis (Joshua); T. Haritunians (Talin); B. McKnight (Barbara); B.M. Psaty (Bruce); K.D. Taylor (Kent); E.L. Thacker (Evan); P. Almgren (Peter); L. Groop (Leif); C. Ladenvall (Claes); M. Boehnke (Michael); A.U. Jackson (Anne); K.L. Mohlke (Karen); H.M. Stringham (Heather); J. Tuomilehto (Jaakko); E.J. Benjamin (Emelia); S.J. Hwang; D. Levy (Daniel); S.R. Preis; R.S. Vasan (Ramachandran Srini); J. Duan (Jubao); P.V. Gejman (Pablo); D.F. Levinson (Douglas); A.R. Sanders (Alan); J. Shi (Jianxin); E.H. Lips (Esther); J.D. McKay (James); A. Agudo (Antonio); L. Barzan (Luigi); V. Bencko (Vladimir); S. Benhamou (Simone); X. Castellsagué (Xavier); C. Canova (Cristina); D.I. Conway (David); E. Fabianova (Eleonora); L. Foretova (Lenka); V. Janout (Vladimir); C.M. Healy (Claire); I. Holcátová (Ivana); K. Kjaerheim (Kristina); P. Lagiou; J. Lissowska (Jolanta); R. Lowry (Ray); T.V. MacFarlane (Tatiana); D. Mates (Dana); L. Richiardi (Lorenzo); P. Rudnai (Peter); N. Szeszenia-Dabrowska (Neonilia); D. Zaridze; A. Znaor (Ariana); M. Lathrop (Mark); P. Brennan (Paul); S. Bandinelli (Stefania); T.M. Frayling (Timothy); J.M. Guralnik (Jack); Y. Milaneschi (Yuri); J.R.B. Perry (John); D. Altshuler (David); R. Elosua (Roberto); S. Kathiresan (Sekar); G. Lucas (Gavin); O. Melander (Olle); V. Salomaa (Veikko); S.M. Schwartz (Stephen); B.F. Voight (Benjamin); B.W.J.H. Penninx (Brenda); J.H. Smit (Johannes); N. Vogelzangs (Nicole); D.I. Boomsma (Dorret); E.J.C. de Geus (Eco); J.M. Vink (Jacqueline); G.A.H.M. Willemsen (Gonneke); S.J. Chanock (Stephen); F. Gu (Fangyi); S.E. Hankinson (Susan); D. Hunter (David); A. Hofman (Albert); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); S. Walter (Stefan); D.I. Chasman (Daniel); B.M. Everett (Brendan); G. Pare (Guillaume); P.M. Ridker (Paul); M.D. Li (Ming); H.H. Maes (Hermine); J. Audrain-Mcgovern (Janet); D. Posthuma (Danielle); L.M. Thornton (Laura); C. Lerman (Caryn); J. Kaprio (Jaakko); J.E. Rose (Jed); J.P.A. Ioannidis (John); P. Kraft (Peter); D.Y. Lin (Dan); P.F. Sullivan (Patrick); C.J. O'Donnell (Christopher)

    2010-01-01

    textabstractConsistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology

  16. The association between pulse wave velocity and cognitive function: the Sydney Memory and Ageing Study.

    Directory of Open Access Journals (Sweden)

    Joel Singer

    Full Text Available OBJECTIVES: Pulse wave velocity (PWV is a measure of arterial stiffness and its increase with ageing has been associated with damage to cerebral microvessels and cognitive impairment. This study examined the relationship between carotid-femoral PWV and specific domains of cognitive function in a non-demented elderly sample. METHOD: Data were drawn from the Sydney Memory and Ageing Study, a cohort study of non-demented community-dwelling individuals aged 70-90 years, assessed in successive waves two years apart. In Wave 2, PWV and cognitive function were measured in 319 participants. Linear regression was used to analyse the cross-sectional relationship between arterial stiffness and cognitive function in the whole sample, and separately for men and women. Analysis of covariance was used to assess potential differences in cognition between subjects with PWV measurements in the top and bottom tertiles of the cohort. Covariates were age, education, body mass index, pulse rate, systolic blood pressure, cholesterol, depression, alcohol, smoking, hormone replacement therapy, apolipoprotein E ε4 genotype, use of anti-hypertensive medications, history of stroke, transient ischemic attack, myocardial infarction, angina, diabetes, and also sex for the whole sample analyses. RESULTS: There was no association between PWV and cognition after Bonferroni correction for multiple testing. When examining this association for males and females separately, an association was found in males, with higher PWV being associated with lower global cognition and memory, however, a significant difference between PWV and cognition between males and females was not found. CONCLUSION: A higher level of PWV was not associated with lower cognitive function in the whole sample.

  17. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

  18. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

    Science.gov (United States)

    Davies, G; Marioni, R E; Liewald, D C; Hill, W D; Hagenaars, S P; Harris, S E; Ritchie, S J; Luciano, M; Fawns-Ritchie, C; Lyall, D; Cullen, B; Cox, S R; Hayward, C; Porteous, D J; Evans, J; McIntosh, A M; Gallacher, J; Craddock, N; Pell, J P; Smith, D J; Gale, C R; Deary, I J

    2016-01-01

    People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal–numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal–numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia. PMID:27046643

  19. Cooling tower wood sampling and analyses: A case study

    International Nuclear Information System (INIS)

    Haymore, J.L.

    1985-01-01

    Extensive wood sampling and analyses programs were initiated on crossflow and counterflow cooling towers that have been in service since 1951 and 1955, respectively. Wood samples were taken from all areas of the towers and were subjected to biological, chemical and physical tests. The tests and results for the analyses are discussed. The results indicate the degree of wood deterioration, and areas of the towers which experience the most advanced degree of degradation

  20. Use of genome-wide association studies for cancer research and drug repositioning.

    Directory of Open Access Journals (Sweden)

    Jizhun Zhang

    Full Text Available Although genome-wide association studies have identified many risk loci associated with colorectal cancer, the molecular basis of these associations are still unclear. We aimed to infer biological insights and highlight candidate genes of interest within GWAS risk loci. We used an in silico pipeline based on functional annotation, quantitative trait loci mapping of cis-acting gene, PubMed text-mining, protein-protein interaction studies, genetic overlaps with cancer somatic mutations and knockout mouse phenotypes, and functional enrichment analysis to prioritize the candidate genes at the colorectal cancer risk loci. Based on these analyses, we observed that these genes were the targets of approved therapies for colorectal cancer, and suggested that drugs approved for other indications may be repurposed for the treatment of colorectal cancer. This study highlights the use of publicly available data as a cost effective solution to derive biological insights, and provides an empirical evidence that the molecular basis of colorectal cancer can provide important leads for the discovery of new drugs.

  1. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

    DEFF Research Database (Denmark)

    Day, Felix R; Thompson, Deborah J; Helgason, Hannes

    2017-01-01

    The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P ... pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare...... variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women...

  2. Analyses of associations between reactive oxygen metabolites and antioxidant capacity and related factors among healthy adolescents.

    Science.gov (United States)

    Tamae, Kazuyoshi; Eto, Toshiharu; Aoki, Kazuhiro; Nakamaru, Shingo; Koshikawa, Kazunori; Sakuma, Kazuhiko; Hirano, Takeshi

    2013-12-01

    Evidence based on epidemiologic investigations using biochemical parameter is meaningful for health promotion and administration among adolescents. We conducted Reactive Oxygen Metabolites (ROM) and Biological Antioxidant Potentials (BAP) tests, along with a questionnaire survey, for a sample of 74 high school students (16.51±0.11 years of aged mean±SE), to investigate the associations between ROM, BAP, and related factors, including BMI and blood biochemical data. Venous blood samples (approximately 7cc) were collected. At the same time, each individual's information was obtained from the questionnaire. The mental health status was investigated using the Center for Epidemiologic Study Depression scale (CES-D) included in the same questionnaire. The mean values and standard errors of all variables were calculated. In addition, the relationships between ROM and BAP with these factors were analyzed. The results revealed the preferred levels of ROM (261.95 ± 9.52 U.CARR) and, BAP (2429.89±53.39 µmol/L) and blood biochemical data. Few significant relationships between two markers and related factors were found. So, we detected a cluster with an imbalance between ROM and BAP, which means low antioxidant ability, whereas the other clusters had conditions with moderate balance or good balance between them. Moreover, we determined the Oxidative stress-Antioxidant capacity ratio (OAR), using the ROM and BAP values, in order to clarify the characteristic of the detected clusters.However, comparative analyses across the three clusters did not yield significant differences in all related factors. No correlations between ROM, BAP and related factors were indicated, although significant association between ROM and BAP was observed (R2=0.1156, R=0.340, P=0.013). The reason for these results can be explained by the influences of good health and young age. On the other hand, present study suggests that some latent problems among adolescents may be related to unhealthy

  3. Correction of population stratification in large multi-ethnic association studies.

    Directory of Open Access Journals (Sweden)

    David Serre

    2008-01-01

    Full Text Available The vast majority of genetic risk factors for complex diseases have, taken individually, a small effect on the end phenotype. Population-based association studies therefore need very large sample sizes to detect significant differences between affected and non-affected individuals. Including thousands of affected individuals in a study requires recruitment in numerous centers, possibly from different geographic regions. Unfortunately such a recruitment strategy is likely to complicate the study design and to generate concerns regarding population stratification.We analyzed 9,751 individuals representing three main ethnic groups - Europeans, Arabs and South Asians - that had been enrolled from 154 centers involving 52 countries for a global case/control study of acute myocardial infarction. All individuals were genotyped at 103 candidate genes using 1,536 SNPs selected with a tagging strategy that captures most of the genetic diversity in different populations. We show that relying solely on self-reported ethnicity is not sufficient to exclude population stratification and we present additional methods to identify and correct for stratification.Our results highlight the importance of carefully addressing population stratification and of carefully "cleaning" the sample prior to analyses to obtain stronger signals of association and to avoid spurious results.

  4. Relationships between menstrual and menopausal attitudes and associated demographic and health characteristics: The Hilo Women’s Health Study

    Science.gov (United States)

    Sievert, Lynnette L.; Brown, Daniel E.; Rahberg, Nichole; Reza, Angela

    2010-01-01

    The objective of this study was to examine the relation of menstrual attitudes to menopausal attitudes and the demographic and health characteristics associated with each. This cross-sectional study consisted of a randomly selected sample of 1824 respondents aged 16 to 100 years in multi-ethnic Hilo, Hawai`i. Women completed questionnaires for demographic and health information, such as age, ethnicity, education, residency in Hawai`i, menopausal status, exercise, and attitudes toward menstruation and menopause. Women more often chose positive terms, such as “natural,” to describe menstruation (60.8%) and menopause (59.4%). In bivariate analyses, post-menopausal women were significantly more likely to have positive menstrual and menopausal attitudes than pre-menopausal women. Factor analyses were used to cluster attitudes followed by linear regression to identify demographic characteristics associated with factor scores. Asian-American ethnicity, higher education, reporting more exercise, and growing up outside of Hawai`i were associated with positive menstrual attitudes. Higher education, older age, post-menopausal status, growing up outside of Hawai`i and having hot flashes were associated with positive menopausal attitudes. Bivariate correlation analyses suggested significant associations between factor scores for menstrual and menopausal attitudes. Both negative and positive menstrual attitudes were positively correlated with the anticipation of menopause, although negative attitudes toward menstruation were negatively correlated with menopause as a positive, natural life event. Demographic variables, specifically education and where one grows up, influenced women’s attitudes toward menstruation and menopause and should be considered for inclusion in subsequent multi-ethnic studies. Further research is also warranted in assessing the relationship between menstrual and menopausal attitudes. PMID:20853216

  5. Groundwater flow analyses in Japan. 1. Case studies in Hokkaido and Northeast Japan

    International Nuclear Information System (INIS)

    Inaba, Hideo; Maekawa, Keisuke; Koide, Kaoru; Yanagizawa, Koichi

    1995-01-01

    An extensive study program has been carried out to estimate hydrogeological characteristics of deep underground in Japan. As a part of this program, groundwater flow analysis in Hokkaido and Northeast Japan were conducted. For the analyses of these area, hydrogeological models representing topography, geology, distribution of hydraulic conductivity were developed using available informations from open literature. By use of these models, steady state three-dimensional groundwater flow under a saturated/unsaturated condition was calculated by means of finite element method. The results are as follows: (1) Distribution of piezometric head corresponds with topography in the study area. (2) Piezometric head distribution is hydrostatic below E.L.-1000m in the study area. (3) Hydraulic gradient in the study area is less than 0.04 below E.L.-500m. (4) Difference of boundary conditions at the shore side of these models does not affect the results of the analyses. (author)

  6. Epizoanthus spp. associations revealed using DNA markers: a case study from Kochi, Japan.

    Science.gov (United States)

    Reimer, James Davis; Hirose, Mamiko; Nishisaka, Taiki; Sinniger, Frederic; Itani, Gyo

    2010-09-01

    Zoanthids (Cnidaria, Hexacorallia) of the genus Epizoanthus are often found in association with other marine invertebrates, including gastropods and hermit crabs. However, little information exists on the specificity and nature of these associations due to a lack of investigation into Epizoanthus species diversity, and the taxonomy of Epizoanthus is therefore confused. In this study, analyses of morphological data (tentacle number, polyp size, etc) and molecular data (mitochondrial cytochrome oxidase subunit 1 = COI, 16S ribosomal DNA = 16S rDNA) were used to examine Epizoanthus specimens from Tosa Bay, Kochi, Japan. The Epizoanthus specimens were found on both live gastropods (Gemmula unedo) and hermit crabs (Paguristes palythophilus) inhabiting G. unedo and G. cosmoi shells. While morphological analyses did not show clear differences between examined specimens, both COI and mt 16S rDNA clearly divided the specimens into two groups, one associated only with hermit crabs (= Epizoanthus sp. C), and another associated only with living gastropods (= Epizoanthus sp. S). Unexpectedly, DNA sequences from both groups did not match with two previously reported Epizoanthus species from Japan (E. indicus, E. ramosus), indicating they both may be undescribed species. These results highlight the utility of DNA "barcoding" of unknown zoanthids, and will provide a foundation for re-examinations of Epizoanthus species diversity and specificity, which will be critical in understanding the evolution of these unique marine invertebrates.

  7. Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE Cohorts

    Directory of Open Access Journals (Sweden)

    Unjin Shim

    2014-12-01

    Full Text Available Metabolic syndrome (MetS is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs, important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs, explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m2. A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10-6, and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10-7, Bonferroni-adjusted p < 0.05. Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF, the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

  8. Association between study design and citation counts of articles published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist.

    Science.gov (United States)

    Allareddy, Veerasathpurush; Lee, Min Kyeong; Shah, Andrea; Elangovan, Satheesh; Lin, Chin-Yu

    2012-01-01

    The scientific community views meta-analyses and systematic reviews, in addition to well-designed randomized controlled clinical trials, as the highest echelon in the continuum of hierarchy of evidence. The objective of this study was to examine the association between different study designs and citation counts of articles published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist. All articles, excluding editorial comments, letters to the editor, commentaries, and special articles, that were published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist during the years 2004 and 2005 were examined in this study. The number of times an article was cited in the first 24 months after its publication was computed. The PubMed database was used to index the study design of the articles. The association between study design and citation counts was examined using the Kruskal-Wallis test. A multivariable negative binomial regression model was used to examine the association between citation count and study design along with several other confounding variables. A total of 624 articles were selected for analysis. Of these, there were 25 meta-analyses or review articles, 42 randomized clinical trials, 59 clinical trials, 48 animal studies, 64 case reports, and 386 quasiexperimental/miscellaneous study designs. The mean ± SD citation count was 1.04 ± 1.46. Nearly half of the articles (n = 311) were not cited even once during the observation period. Case reports were cited less frequently than meta-analyses or reviews (incident risk ratio, 0.37; 95% confidence interval, 0.19 to 0.72; P = .003), even after adjusting for other independent variables. Among various study designs, meta-analyses and review articles are more likely to be cited in the first 24 months after publication. This study demonstrates the importance of publishing more meta-analyses and review articles for quicker dissemination of

  9. Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

    Directory of Open Access Journals (Sweden)

    Wayland Hsiao

    2009-01-01

    Full Text Available HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs and corresponding 95% confidence intervals (CI. The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5. In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.

  10. Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

    Science.gov (United States)

    Hsiao, Wayland; Anastasia, Katrina; Hall, John; Goodman, Michael; Rimland, David; Ritenour, Chad W. M.; Issa, Muta M.

    2009-01-01

    HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients. PMID:19219374

  11. Intention stability assessed using residual change scores moderates the intention-behaviour association: a prospective cohort study.

    Science.gov (United States)

    Rowan, Alicia A; McDermott, Máirtín S; Allen, Mark S

    2017-12-01

    Intention stability is considered to be one of the key pre-requisites for a strong association between intention and behaviour. It has been claimed, however, that studies examining the moderating impact of intention stability may be invalid, as they have relied on statistically inferior methods. Residual change scores have been suggested as a more appropriate method of measuring change (or lack thereof) in constructs. The aim of the current study, therefore, is to test whether intention stability, calculated using residual change scores, moderates the intention-physical activity behaviour association. A total of 163 participants (124 women, 39 men) completed questionnaires online at three time points separated by 14 day intervals. The moderating impact of intention stability was assessed using multiple linear regression followed up using simple slope analyses to identify the direction of any effect. The interaction of intention and intention stability was found to significantly improve the overall model fit. Intentions had a stronger positive association with behaviour when intentions were more stable than when they were more unstable. However, sensitivity analyses revealed that the association was not robust and reduced to non-significant with the removal of potential multivariate outliers. Future research should use residual change scores as the preferred method of assessing intention stability.

  12. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes.

    Science.gov (United States)

    Poole, Robin; Kennedy, Oliver J; Roderick, Paul; Fallowfield, Jonathan A; Hayes, Peter C; Parkes, Julie

    2017-11-22

    Objectives  To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes. Design  Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome. Data sources  PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references. Eligibility criteria for selecting studies  Meta-analyses of both observational and interventional studies that examined the associations between coffee consumption and any health outcome in any adult population in all countries and all settings. Studies of genetic polymorphisms for coffee metabolism were excluded. Results  The umbrella review identified 201 meta-analyses of observational research with 67 unique health outcomes and 17 meta-analyses of interventional research with nine unique outcomes. Coffee consumption was more often associated with benefit than harm for a range of health outcomes across exposures including high versus low, any versus none, and one extra cup a day. There was evidence of a non-linear association between consumption and some outcomes, with summary estimates indicating largest relative risk reduction at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83 (95% confidence interval 0.79 to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an 18% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also associated with a lower risk of several specific cancers and neurological, metabolic, and liver conditions. Harmful associations were largely nullified by adequate adjustment for smoking, except in pregnancy, where high versus low/no consumption was associated with low birth weight (odds ratio 1.31, 95% confidence interval 1.03 to 1.67), preterm birth in the first (1.22, 1.00 to 1.49) and second (1

  13. Quasi-causal associations of physical activity and neighborhood walkability with body mass index: a twin study.

    Science.gov (United States)

    Duncan, Glen E; Cash, Stephanie Whisnant; Horn, Erin E; Turkheimer, Eric

    2015-01-01

    Physical activity, neighborhood walkability, and body mass index (BMI, kg/m(2)) associations were tested using quasi-experimental twin methods. We hypothesized that physical activity and walkability were independently associated with BMI within twin pairs, controlling for genetic and environmental background shared between them. Data were from 6376 (64% female; 58% identical) same-sex pairs, University of Washington Twin Registry, 2008-2013. Neighborhood walking, moderate-to-vigorous physical activity (MVPA), and BMI were self-reported. Residential address was used to calculate walkability. Phenotypic (non-genetically informed) and biometric (genetically informed) regression was employed, controlling for age, sex, and race. Walking and MVPA were associated with BMI in phenotypic analyses; associations were attenuated but significant in biometric analyses (PsWalkability was not associated with BMI, however, was associated with walking (but not MVPA) in both phenotypic and biometric analyses (Pswalkability is not associated with BMI, it is associated with neighborhood walking (but not MVPA) accounting for shared background, suggesting a causal relationship between them. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Assessing the validity of road safety evaluation studies by analysing causal chains.

    Science.gov (United States)

    Elvik, Rune

    2003-09-01

    This paper discusses how the validity of road safety evaluation studies can be assessed by analysing causal chains. A causal chain denotes the path through which a road safety measure influences the number of accidents. Two cases are examined. One involves chemical de-icing of roads (salting). The intended causal chain of this measure is: spread of salt --> removal of snow and ice from the road surface --> improved friction --> shorter stopping distance --> fewer accidents. A Norwegian study that evaluated the effects of salting on accident rate provides information that describes this causal chain. This information indicates that the study overestimated the effect of salting on accident rate, and suggests that this estimate is influenced by confounding variables the study did not control for. The other case involves a traffic club for children. The intended causal chain in this study was: join the club --> improve knowledge --> improve behaviour --> reduce accident rate. In this case, results are rather messy, which suggests that the observed difference in accident rate between members and non-members of the traffic club is not primarily attributable to membership in the club. The two cases show that by analysing causal chains, one may uncover confounding factors that were not adequately controlled in a study. Lack of control for confounding factors remains the most serious threat to the validity of road safety evaluation studies.

  15. Genome-wide association study of retinopathy in individuals without diabetes.

    Directory of Open Access Journals (Sweden)

    Richard A Jensen

    Full Text Available Mild retinopathy (microaneurysms or dot-blot hemorrhages is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS of mild retinopathy in persons without diabetes.A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9 on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error, p = 6.6×10(-9. Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%, the quality of the imputation was moderate (r(2 ∼0.7, and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

  16. Infrared study of new star cluster candidates associated to dusty globules

    Science.gov (United States)

    Soto King, P.; Barbá, R.; Roman-Lopes, A.; Jaque, M.; Firpo, V.; Nilo, J. L.; Soto, M.; Minniti, D.

    2014-10-01

    We present results from a study of a sample of small star clusters associated to dusty globules and bright-rimmed clouds that have been observed under ESO/Chile public infrared survey Vista Variables in the Vía Láctea (VVV). In this short communication, we analyse the near-infrared properties of a set of four small clusters candidates associated to dark clouds. This sample of clusters associated to dusty globules are selected from the new VVV stellar cluster candidates developed by members of La Serena VVV Group (Barbá et al. 2014). Firstly, we are producing color-color and color-magnitude diagrams for both, cluster candidates and surrounding areas for comparison through PSF photometry. The cluster positions are determined from the morphology on the images and also from the comparison of the observed luminosity function for the cluster candidates and the surrounding star fields. Now, we are working in the procedures to establish the full sample of clusters to be analyzed and methods for subtraction of the star field contamination. These clusters associated to dusty globules are simple laboratories to study the star formation relatively free of the influence of large star-forming regions and populous clusters, and they will be compared with those clusters associated to bright-rimmed globules, which are influenced by the energetic action of nearby O and B massive stars.

  17. A comparison of Cox and logistic regression for use in genome-wide association studies of cohort and case-cohort design.

    Science.gov (United States)

    Staley, James R; Jones, Edmund; Kaptoge, Stephen; Butterworth, Adam S; Sweeting, Michael J; Wood, Angela M; Howson, Joanna M M

    2017-06-01

    Logistic regression is often used instead of Cox regression to analyse genome-wide association studies (GWAS) of single-nucleotide polymorphisms (SNPs) and disease outcomes with cohort and case-cohort designs, as it is less computationally expensive. Although Cox and logistic regression models have been compared previously in cohort studies, this work does not completely cover the GWAS setting nor extend to the case-cohort study design. Here, we evaluated Cox and logistic regression applied to cohort and case-cohort genetic association studies using simulated data and genetic data from the EPIC-CVD study. In the cohort setting, there was a modest improvement in power to detect SNP-disease associations using Cox regression compared with logistic regression, which increased as the disease incidence increased. In contrast, logistic regression had more power than (Prentice weighted) Cox regression in the case-cohort setting. Logistic regression yielded inflated effect estimates (assuming the hazard ratio is the underlying measure of association) for both study designs, especially for SNPs with greater effect on disease. Given logistic regression is substantially more computationally efficient than Cox regression in both settings, we propose a two-step approach to GWAS in cohort and case-cohort studies. First to analyse all SNPs with logistic regression to identify associated variants below a pre-defined P-value threshold, and second to fit Cox regression (appropriately weighted in case-cohort studies) to those identified SNPs to ensure accurate estimation of association with disease.

  18. Oral contraceptive use is associated with prostate cancer: an ecological study.

    Science.gov (United States)

    Margel, David; Fleshner, Neil E

    2011-01-01

    Background Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa). Objectives To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality. Methods The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed by individual nations and by continents worldwide. Results OC use was significantly associated with prostate cancer incidence and mortality in the individual nations worldwide (r=0.61 and r=0.53, respectively; pnation's wealth. Conclusion A significant association between OCs and PCa has been shown. It is hypothesised that the OC effect may be mediated through environmental oestrogen levels; this novel concept is worth further investigation.

  19. Prevalence and factors associated with neck pain: a population-based study.

    Science.gov (United States)

    Genebra, Caio Vitor Dos Santos; Maciel, Nicoly Machado; Bento, Thiago Paulo Frascareli; Simeão, Sandra Fiorelli Almeida Penteado; Vitta, Alberto De

    Neck pain is a musculoskeletal condition with high prevalence that may affect the physical, social, and psychological aspects of the individual, contributing to the increase in costs in society and business. To determine the prevalence of neck pain and associated factors in a population-based sample of adults aged 20 and more. Cross-sectional study based on a population survey. A total number of 600 individuals were interviewed in their homes, and the following data were collected: (1) participant characteristics (demographic, socioeconomic, and work-related aspects) using a pre-coded questionnaire; (2) physical activity level using the IPAQ; and (3) musculoskeletal symptoms using the Nordic questionnaire. Descriptive, bivariate, and Poisson regression analyses were performed. The prevalence of neck pain was 20.3% (95% CI 17.3-23.7). The adjusted analyses showed that individuals who were widowers or separated (PR=2.26; 1.42-5.88), had a low income (PR=1.32; 1.22-6.27) or low educational level (PR=1.83; 1.02-5.26), worked while sitting and leaning (PR=1.55; 1.08-2.40), and who reported having two or more diseases (PR=1.71; 1.55-6.31) remained associated with neck pain. This study reveals the high prevalence of neck pain and remarkable association with widowed/separated people who have low income and low educational level, who perform their occupational activities in sitting and leaning positions, and who reported having two or more diseases. Knowledge of these risk factors will contribute to the development of forms of assistance in which neck pain can be prevented and better managed. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

  20. Factors associated with occupational strain among Chinese teachers: a cross-sectional study.

    Science.gov (United States)

    Yang, X; Wang, L; Ge, C; Hu, B; Chi, T

    2011-02-01

    With the reform of the education system in China, teachers are suffering from more occupational strain, which is believed to impair their working state indirectly and affect their health. This study assessed occupational strain and explored the related factors among Chinese teachers. Cross-sectional with cluster sampling. The study population was composed of 3570 school teachers working in 64 primary and middle schools in Heping District in Shenyang, China. Data were collected using a self-administered questionnaire (the Chinese version of the Occupational Stress Inventory scale). Multivariate linear regression analyses were performed to study the factors related to occupational strain. The average score on the Personal Strain Questionnaire (PSQ) for the whole study population was 106.5 (107.5 in men and 106.3 in women). Teachers with chronic disease, a greater number of days of sick leave, recent experience of a stressful life event and divorced/separated/widowed status tended to suffer greater strain than their peers. Regression analyses showed that the PSQ score was significantly associated with role overload, role boundary, responsibility and physical environment, and inversely associated with recreation and rational coping. The most crucial predictors of occupational strain were chronic disease, days of sick leave, recent experience of a stressful life event and marital status. Being a class teacher was the strongest indicator of interpersonal strain. Self-care was associated with vocational strain and psychological strain, and inversely associated with physical strain. Most teachers in this study experienced a high degree of occupational strain. Chronic disease, days of sick leave, recent experience of a stressful life event and divorced/separated/widowed status played prominent roles in occupational strain. In addition, role overload, role boundary, responsibility and physical environment induce occupational strain, while recreation and rational coping have

  1. Positive associations between consumerism and tobacco and alcohol use in early adolescence: cross-sectional study.

    Science.gov (United States)

    Sweeting, Helen N; Bhaskar, Abita; Hunt, Kate

    2012-01-01

    There is concern about the negative impact of modern consumer culture on young people's mental health, but very few studies have investigated associations with substance use. In those which have, positive associations have been attributed to attempts to satisfy the unmet needs of more materialistic individuals. This study examines associations between different dimensions of consumerism and tobacco and alcohol use among Scottish early adolescents. Cross-sectional study. 2937 (92% of those eligible) secondary school pupils (ages 12-14) completed questionnaires in examination conditions. Analyses were restricted to those with complete data on all relevant variables (N=2736 smoking; N=2737 drinking). Dependent variables comprised ever smoking and current drinking. Measures of consumerism comprised number of 'premium' (range 0-7) and 'standard' (range 0-5) material possessions and three Consumer Involvement subscales, 'dissatisfaction', 'consumer orientation' and 'brand awareness' (each range 3-12). Analyses also included school-year group and family affluence. Ever smoking and current drinking were both more prevalent among adolescents with more 'premium' and 'standard' material possessions, greater consumer 'dissatisfaction' and 'brand awareness' (mutually adjusted analyses including school-year group and family affluence). The strongest relationships occurred for 'brand awareness': for each unit increase in 'brand awareness' the ORs (95% CI) of ever smoking were 1.17 (1.08 to 1.26) and 1.23 (1.14 to 1.33) in males and females, respectively; and those for drinking were 1.15 (1.08 to 1.23) and 1.21 (1.13 to 1.30). 'Brand awareness' had an equal or stronger relationship with both smoking and drinking than did family affluence. These results suggest aassociations between consumerism and both smoking and drinking might arise because adolescent identities incorporate both consumerism and substance use, or be the result of promotion (indirectly in the case of tobacco

  2. A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

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    Johanna Hass

    Full Text Available Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328. A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170 on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10 had p-values between 6.75×10(-6 and 8.3×10(-7. Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings

  3. Associations between Distal Upper Extremity Job Physical Factors and Psychosocial Measures in a Pooled Study

    Directory of Open Access Journals (Sweden)

    Matthew S. Thiese

    2015-01-01

    Full Text Available Introduction. There is an increasing body of literature relating musculoskeletal diseases to both job physical exposures and psychosocial outcomes. Relationships between job physical exposure measures and psychosocial factors have not been well examined or quantified. These exploratory analyses evaluate relationships between quantified exposures and psychosocial outcomes. Methods. Individualized quantification of duration, repetition, and force and composite scores of the Strain Index (SI and the Threshold Limit Value for Hand Activity Level (TLV for HAL were compared to 10 psychosocial measures. Relationships and predicted probabilities were assessed using ordered logistic regression. Analyses were adjusted for age, BMI, and gender. Results and Discussion. Among 1834 study participants there were multiple statistically significant relationships. In general, as duration, repetition, and force increased, psychosocial factors worsened. However, general health and mental exhaustion improved with increasing job exposures. Depression was most strongly associated with increased repetition, while physical exhaustion was most strongly associated with increased force. SI and TLV for HAL were significantly related to multiple psychosocial factors. These relationships persisted after adjustment for strong confounders. Conclusion. This study quantified multiple associations between job physical exposures and occupational and nonoccupational psychosocial factors. Further research is needed to quantify the impacts on occupational health outcomes.

  4. Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.

    Science.gov (United States)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika; Wang, Zhaoming; Henriksson, Roger; Hallmans, Göran; Bondy, Melissa L; Johansen, Christoffer; Feychting, Maria; Ahlbom, Anders; Kitahara, Cari M; Wang, Sophia S; Ruder, Avima M; Carreón, Tania; Butler, Mary Ann; Inskip, Peter D; Purdue, Mark; Hsing, Ann W; Mechanic, Leah; Gillanders, Elizabeth; Yeager, Meredith; Linet, Martha; Chanock, Stephen J; Hartge, Patricia; Rajaraman, Preetha

    2013-05-15

    Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours. Copyright © 2012 UICC.

  5. Associations between Narrow Angle and Adult Anthropometry: The Liwan Eye Study

    Science.gov (United States)

    Jiang, Yuzhen; He, Mingguang; Friedman, David S.; Khawaja, Anthony P.; Lee, Pak Sang; Nolan, Winifred P.; Yin, Qiuxia; Foster, Paul J.

    2015-01-01

    Purpose To assess the associations between narrow angle and adult anthropometry. Methods Chinese adults aged 50 years and older were recruited from a population-based survey in the Liwan District of Guangzhou, China. Narrow angle was defined as the posterior trabecular meshwork not visible under static gonioscopy in at least three quadrants (i.e. a circumference of at least 270°). Logistic regression models were used to examine the associations between narrow angle and anthropomorphic measures (height, weight and body mass index, BMI). Results Among the 912 participants, lower weight, shorter height, and lower BMI were significantly associated with narrower angle width (tests for trend: mean angle width in degrees vs weight p<0.001; vs height p<0.001; vs BMI p = 0.012). In univariate analyses, shorter height, lower weight and lower BMI were all significantly associated with greater odds of narrow angle. The crude association between height and narrow angle was largely attributable to a stronger association with age and sex. Lower BMI and weight remained significantly associated with narrow angle after adjustment for height, age, sex, axial ocular biometric measures and education. In analyses stratified by sex, the association between BMI and narrow angle was only observed in women. Conclusion Lower BMI and weight were associated with significantly greater odds of narrow angle after adjusting for age, education, axial ocular biometric measures and height. The odds of narrow angle increased 7% per 1 unit decrease in BMI. This association was most evident in women. PMID:24707840

  6. Methods and procedures for shielding analyses for the SNS

    International Nuclear Information System (INIS)

    Popova, I.; Ferguson, F.; Gallmeier, F.X.; Iverson, E.; Lu, Wei

    2011-01-01

    In order to provide radiologically safe Spallation Neutron Source operation, shielding analyses are performed according to Oak Ridge National Laboratory internal regulations and to comply with the Code of Federal Regulations. An overview of on-going shielding work for the accelerator facility and neutrons beam lines, methods used for the analyses, and associated procedures and regulations are presented. Methods used to perform shielding analyses are described as well. (author)

  7. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    OpenAIRE

    Okbay, Aysu; Baselmans, B.M.L. (Bart M.L.); Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel; Fontana, M.A. (Mark Alan); Meddens, S.F.W. (S. Fleur W.); Linnér, R.K. (Richard Karlsson); Rietveld, C.A. (Cornelius A); Derringer, J.; Gratten, Jacob; Lee, James J.; Liu, J.Z. (Jimmy Z); Vlaming, Ronald; SAhluwalia, T. (Tarunveer)

    2016-01-01

    textabstractVery few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associ...

  8. Large-scale association study for structural soundness and leg locomotion traits in the pig

    Directory of Open Access Journals (Sweden)

    Serenius Timo

    2009-01-01

    Full Text Available Abstract Background Identification and culling of replacement gilts with poor skeletal conformation and feet and leg (FL unsoundness is an approach used to reduce sow culling and mortality rates in breeding stock. Few candidate genes related to soundness traits have been identified in the pig. Methods In this study, 2066 commercial females were scored for 17 traits describing body conformation and FL structure, and were used for association analyses. Genotyping of 121 SNPs derived from 95 genes was implemented using Sequenom's MassARRAY system. Results Based on the association results from single trait and principal components using mixed linear model analyses and false discovery rate testing, it was observed that APOE, BMP8, CALCR, COL1A2, COL9A1, DKFZ, FBN1 and VDBP were very highly significantly (P ALOX5, BMP8, CALCR, OPG, OXTR and WNT16 were very highly significantly (P APOE, CALCR, COL1A2, GNRHR, IHH, MTHFR and WNT16 were highly significantly (P CALCR and COL1A2 on SSC9 was detected, and haplotype -ACGACC- was highly significantly (P Conclusion The present findings provide a comprehensive list of candidate genes for further use in fine mapping and biological functional analyses.

  9. Heritability and Genome-Wide Association Analyses of Serum Uric Acid in Middle and Old-Aged Chinese Twins

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    Weijing Wang

    2018-03-01

    Full Text Available Serum uric acid (SUA, as the end product of purine metabolism, has proven emerging roles in human disorders. Here based on a sample of 379 middle and old-aged Chinese twin pairs, we aimed to explore the magnitude of genetic impact on SUA variation by performing sex-limitation twin modeling analyses and further detect specific genetic variants related to SUA by conducting a genome-wide association study. Monozygotic (MZ twin correlation for SUA level (rMZ = 0.56 was larger than for dizygotic (DZ twin correlation (rDZ = 0.39. The common effects sex-limitation model provided the best fit with additive genetic parameter (A accounting for 46.3%, common or shared environmental parameter (C accounting for 26.3% and unique/nonshared environmental parameter (E accounting for 27.5% for females and 29.9, 33.1, and 37.0% for males, respectively. Although no SUA-related genetic variants reached genome-wide significance level, 25 SNPs were suggestive of association (P < 1 × 10−5. Most of the SNPs were located in an intronic region and detected to have regulatory effects on gene transcription. The cell-type specific enhancer of skeletal muscle was detected which has been reported to implicate SUA. Two promising genetic regions on chromosome 17 around rs2253277 and chromosome 14 around rs11621523 were found. Gene-based analysis found 167 genes nominally associated with SUA level (P < 0.05, including PTGR2, ENTPD5, well-known SLC2A9, etc. Enrichment analysis identified one pathway of transmembrane transport of small molecules and 20 GO gene sets involving in ion transport, transmembrane transporter activity, hydrolase activity acting on acid anhydrides, etc. In conclusion, SUA shows moderate heritability in women and low heritability in men in the Chinese population and genetic variations are significantly involved in functional genes and regulatory domains that mediate SUA level. Our findings provide clues to further elucidate molecular

  10. Association of polymorphisms of the CHI3L1 gene with asthma and atopy: a populations-based study of 6514 Danish adults

    DEFF Research Database (Denmark)

    Rathcke, Camilla Noelle; Holmkvist, Johan; Husmoen, Lise Lotte N

    2009-01-01

    associated with FEV1. However, two SNPs (rs10399931 and rs4950930) appeared to be significantly associated with FEV(1)/FVC-ratio. Subgroup analyses of never-smokers did not consistently influence the associations in an either positively og negatively way. CONCLUSIONS: In contrast to previous studies, the rs...

  11. SNPpy--database management for SNP data from genome wide association studies.

    Directory of Open Access Journals (Sweden)

    Faheem Mitha

    Full Text Available BACKGROUND: We describe SNPpy, a hybrid script database system using the Python SQLAlchemy library coupled with the PostgreSQL database to manage genotype data from Genome-Wide Association Studies (GWAS. This system makes it possible to merge study data with HapMap data and merge across studies for meta-analyses, including data filtering based on the values of phenotype and Single-Nucleotide Polymorphism (SNP data. SNPpy and its dependencies are open source software. RESULTS: The current version of SNPpy offers utility functions to import genotype and annotation data from two commercial platforms. We use these to import data from two GWAS studies and the HapMap Project. We then export these individual datasets to standard data format files that can be imported into statistical software for downstream analyses. CONCLUSIONS: By leveraging the power of relational databases, SNPpy offers integrated management and manipulation of genotype and phenotype data from GWAS studies. The analysis of these studies requires merging across GWAS datasets as well as patient and marker selection. To this end, SNPpy enables the user to filter the data and output the results as standardized GWAS file formats. It does low level and flexible data validation, including validation of patient data. SNPpy is a practical and extensible solution for investigators who seek to deploy central management of their GWAS data.

  12. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents

    Science.gov (United States)

    Schoenaker, Danielle AJM; Jackson, Caroline A; Rowlands, Jemma V; Mishra, Gita D

    2014-01-01

    Background: Age at natural menopause (ANM) is considered a marker of biological ageing and is increasingly recognized as a sentinel for chronic disease risk in later life. Socioeconomic position (SEP) and lifestyle factors are thought to be associated with ANM. Methods: We performed a systematic review and meta-analyses to determine the overall mean ANM, and the effect of SEP and lifestyle factors on ANM by calculating the weighted mean difference (WMD) and pooling adjusted hazard ratios. We explored heterogeneity using meta-regression and also included unpublished findings from the Australian Longitudinal Study on Women’s Health. Results: We identified 46 studies across 24 countries. Mean ANM was 48.8 years [95% confidence interval (CI): 48.3, 49.2], with between-study heterogeneity partly explained by geographical region. ANM was lowest among African, Latin American, Asian and Middle Eastern countries and highest in Europe and Australia, followed by the USA. Education was associated with later ANM (WMD middle vs low education 0.30, 95% CI: 0.10, 0.51; high vs low education 0.64, 95% CI 0.26, 1.02). A similar dose-response relationship was also observed for occupation. Smoking was associated with a 1-year reduction of ANM (WMD: -0.91, 95% CI: –1.34, –0.48). Being overweight and moderate/high physical activity were modestly associated with later ANM, but findings were less conclusive. Conclusions: ANM varies across populations, partly due to differences across geographical regions. SEP and some lifestyle factors are associated with ANM, but further research is needed to examine the impact of the associations between risk factors and ANM on future health outcomes. PMID:24771324

  13. Evaluation of the association between acne and smoking: systematic review and meta-analysis of cross-sectional studies

    Directory of Open Access Journals (Sweden)

    Alice Mannocci

    2010-09-01

    Full Text Available

    Background: Acne vulgaris is one of the most common skin diseases with a multifactorial pathogenesis. Examination of the literature regarding the contribution of smoking to acne shows contradictory results. The aim of this study was to undertake a systematic review of the literature and meta-analysis about the association between acne and smoking.

    Methods: A systematic review and meta-analysis, when possible were performed. The literature review was based on Pubmed, Scopus and Google Scholar searches using the keywords “(smoking OR tobacco OR nicotine OR cigarettes AND acne”. Only cross-sectional studies were included. Meta-analyses were performed using the RevMan software version 5 for Windows. Four different meta-analyses were carried out: one evaluating the association between smoking habit and acne, one including data stratified by gender, one for studies with a quality score > 6, and one relating to acne classification.

    Results: Six studies were selected. The first meta-analysis, including all studies, showed a non significant role of smoke in the development of acne: OR 1.05 (95% CI: 0.66–1.67 with random effect estimate. The second meta-analyses, including data stratified by gender, showed a OR=0.99 (95% CI: 0.57–1.73 for males and a OR of 1.45 (95% CI: 0.08–24.64 for females, using random effect for the heterogeneity in both cases. The third meta-analysis, included studies with a quality score >6 resulted in an estimated OR= 0.69 (95% CI: 0.55–0.85: in this case it was possible to use the fixed effect estimate. The last meta-analysis, concerning the severity grading, showed a non-significant result: OR=1.09 (95% CI: 0.61–1.95 using the random effect approach.

    Conclusions: The first two meta-analyses found no signification association between smoking and

  14. The association between Colombian medical students' healthy personal habits and a positive attitude toward preventive counseling: cross-sectional analyses

    Science.gov (United States)

    Duperly, John; Lobelo, Felipe; Segura, Carolina; Sarmiento, Francisco; Herrera, Deisy; Sarmiento, Olga L; Frank, Erica

    2009-01-01

    Background Physician-delivered preventive counseling is important for the prevention and management of chronic diseases. Data from the U.S. indicates that medical students with healthy personal habits have a better attitude towards preventive counseling. However, this association and its correlates have not been addressed in rapidly urbanized settings where chronic disease prevention strategies constitute a top public health priority. This study examines the association between personal health practices and attitudes toward preventive counseling among first and fifth-year students from 8 medical schools in Bogotá, Colombia. Methods During 2006, a total of 661 first- and fifth-year medical students completed a culturally adapted Spanish version of the "Healthy Doctor = Healthy Patient" survey (response rate = 78%). Logistic regression analyses were used to assess the association between overall personal practices on physical activity, nutrition, weight control, smoking, alcohol use (main exposure variable) and student attitudes toward preventive counseling on these issues (main outcome variable), stratified by year of training and adjusting by gender and medical training-related factors (basic knowledge, perceived adequacy of training and perception of the school's promotion on each healthy habit). Results The median age and percentage of females for the first- and fifth-year students were 21 years and 59.5% and 25 years and 65%, respectively. After controlling for gender and medical training-related factors, consumption of ≥ 5 daily servings of fruits and/or vegetables, not being a smoker or binge drinker were associated with a positive attitude toward counseling on nutrition (OR = 4.71; CI = 1.6–14.1; p = 0.006 smoking (OR = 2.62; CI = 1.1–5.9; p = 0.022), and alcohol consumption (OR = 2.61; CI = 1.3–5.4; p = 0.009), respectively. Conclusion As for U.S. physician and medical students, a positive association was found between the personal health habits of

  15. A Study for Visual Realism of Designed Pictures on Computer Screens by Investigation and Brain-Wave Analyses.

    Science.gov (United States)

    Wang, Lan-Ting; Lee, Kun-Chou

    2016-08-01

    In this article, the visual realism of designed pictures on computer screens is studied by investigation and brain-wave analyses. The practical electroencephalogram (EEG) measurement is always time-varying and fluctuating so that conventional statistical techniques are not adequate for analyses. This study proposes a new scheme based on "fingerprinting" to analyze the EEG. Fingerprinting is a technique of probabilistic pattern recognition used in electrical engineering, very like the identification of human fingerprinting in a criminal investigation. The goal of this study was to assess whether subjective preference for pictures could be manifested physiologically by EEG fingerprinting analyses. The most important advantage of the fingerprinting technique is that it does not require accurate measurement. Instead, it uses probabilistic classification. Participants' preference for pictures can be assessed using fingerprinting analyses of physiological EEG measurements. © The Author(s) 2016.

  16. Genome-Wide Association Study of the Genetic Determinants of Emphysema Distribution.

    Science.gov (United States)

    Boueiz, Adel; Lutz, Sharon M; Cho, Michael H; Hersh, Craig P; Bowler, Russell P; Washko, George R; Halper-Stromberg, Eitan; Bakke, Per; Gulsvik, Amund; Laird, Nan M; Beaty, Terri H; Coxson, Harvey O; Crapo, James D; Silverman, Edwin K; Castaldi, Peter J; DeMeo, Dawn L

    2017-03-15

    Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe-predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. To identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin-deficient smokers. A total of 11,532 subjects with complete genotype and computed tomography densitometry data in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]; non-Hispanic white and African American), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints), and GenKOLS (Genetics of Chronic Obstructive Lung Disease) studies were analyzed. Two computed tomography scan emphysema distribution measures (difference between upper-third and lower-third emphysema; ratio of upper-third to lower-third emphysema) were tested for genetic associations in all study subjects. Separate analyses in each study population were followed by a fixed effect metaanalysis. Single-nucleotide polymorphism-, gene-, and pathway-based approaches were used. In silico functional evaluation was also performed. We identified five loci associated with emphysema distribution at genome-wide significance. These loci included two previously reported associations with COPD susceptibility (4q31 near HHIP and 15q25 near CHRNA5) and three new associations near SOWAHB, TRAPPC9, and KIAA1462. Gene set analysis and in silico functional evaluation revealed pathways and cell types that may potentially contribute to the pathogenesis of emphysema distribution. This multicohort genome-wide association study identified new genomic loci associated with differential emphysematous destruction throughout the lungs. These findings may point to new biologic pathways on which to expand diagnostic and therapeutic

  17. The Association between Meditation Practice and Job Performance: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Koichiro Shiba

    Full Text Available Many previous studies have shown that meditation practice has a positive impact on cognitive and non-cognitive functioning, which are related to job performance. Thus, the aims of this study were to (1 estimate the prevalence of meditation practice, (2 identify the characteristics of individuals who practice meditation, and (3 examine the association between meditation practice and job performance. Two population-based, cross-sectional surveys were conducted. In study 1, we examined the prevalence of meditation practice and the characteristics of the persons practicing meditation; in Study 2, we examined the association between meditation practice and job performance. The outcome variables included work engagement, subjective job performance, and job satisfaction. The Utrecht Work Engagement Scale was used to assess work engagement, the World Health Organization Health and Work Performance Questionnaire (HPQ was used to measure subjective job performance, and a scale developed by the Japanese government was used to assess job satisfaction. Hierarchical multiple regression analyses were used in Study 2. Demographic characteristics and behavioral risk factors were included as covariates in the analyses. The results of Study 1 indicated that 3.9% of persons surveyed (n = 30,665 practiced meditation; these individuals were younger and had a higher education, higher household income, higher stress level, and lower body mass index than those who did not practice meditation. The results of Study 2 (n = 1,470 indicated that meditation practice was significantly predictive of work engagement (β = 0.112, p < .001, subjective job performance (β = 0.116, p < .001, and job satisfaction (β = 0.079, p = .002, even after adjusting for covariates (β = 0.083, p < .001; β = 0.104, p < .001; β = 0.060, p = .015, respectively. The results indicate that meditation practice may positively influence job performance, including job satisfaction, subjective job

  18. Study of thermal-hydraulic analyses with CIP method

    International Nuclear Information System (INIS)

    Doi, Yoshihiro

    1996-09-01

    New type of numerical scheme CIP has been proposed for solving hyperbolic type equations and the CIP is focused on as a less numerical diffusive scheme. C-CUP method with the CIP scheme is adopted to numerical simulations that treat compressible and incompressible fluids, phase change phenomena and Mixture fluids. To evaluate applicabilities of the CIP scheme and C-CUP method for thermal hydraulic analyses related to Fast Breeder Reactors (FBRs), the scheme and the method were reviewed. Feature of the CIP scheme and procedure of the C-CUP method were presented. The CIP scheme is used to solve linear hyperbolic type equations for advection term in basic equations of fluids. Key issues of the scheme is that profile between grid points is described to solve the equation by cubic polynomial and spatial derivatives of the polynomial. The scheme can capture steep change of solution and suppress numerical error. In the C-CUP method, the basic equations of fluids are divided into advection terms and the other terms. The advection terms is solved with CIP scheme and the other terms is solved with difference method. The C-CUP method is robust for numerical instability, but mass of fluid will be in unfair preservation with nonconservative equations for fluids. Numerical analyses with the CIP scheme and the C-CUP method has been performed for phase change, mixture and moving object. These analyses are depend on characteristics of that the scheme and the method are robust for steep change of density and useful for interface tracking. (author)

  19. Methodological issues of genetic association studies.

    Science.gov (United States)

    Simundic, Ana-Maria

    2010-12-01

    Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.

  20. The association between depression and eating styles in four European countries: The MooDFOOD prevention study.

    Science.gov (United States)

    Paans, Nadine P G; Bot, Mariska; Brouwer, Ingeborg A; Visser, Marjolein; Roca, Miquel; Kohls, Elisabeth; Watkins, Ed; Penninx, Brenda W J H

    2018-05-01

    Depression, one of the most prevalent and disabling disorders in Europe, is thought to be associated with unhealthy eating styles. As prevalence of depression and eating styles potentially differ across Europe, the current study aimed to investigate in a large, European sample, the associations of history of major depressive disorder and depression severity with unhealthy eating styles. Baseline data of the MooDFOOD prevention study was used. The current analysis included 990 participants of four European countries (The Netherlands, United Kingdom, Germany, Spain). Analyses of Covariance and linear regression analyses were performed with depression history or depression severity as determinants, and emotional, uncontrolled, and cognitive restrained eating (Three Factor Eating Questionnaire Revised, 18 item) as outcomes. Depression history and severity were associated with more emotional and uncontrolled eating and with less cognitive restrained eating. Mood, somatic, and cognitive symptom clusters were also associated with more emotional and uncontrolled eating, and with less cognitive restrained eating. The somatic depressive symptoms "increased appetite" and "increased weight" were more strongly associated to unhealthy eating styles compared to other symptoms. No differences in associations between depression and unhealthy eating were found between European countries. Our results suggest that depression is related to more unhealthy eating styles. Diminishing unhealthy eating styles in subthreshold depressed persons could potentially reduce adverse health consequences like weight gain, unhealthy dietary patterns and weight-related diseases. It is also possible that interventions that decrease depressive symptoms can lead to a decrease in unhealthy eating styles. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Associations between food and beverage groups and major diet-related chronic diseases: an exhaustive review of pooled/meta-analyses and systematic reviews.

    Science.gov (United States)

    Fardet, Anthony; Boirie, Yves

    2014-12-01

    Associations between food and beverage groups and the risk of diet-related chronic disease (DRCD) have been the subject of intensive research in preventive nutrition. Pooled/meta-analyses and systematic reviews (PMASRs) aim to better characterize these associations. To date, however, there has been no attempt to synthesize all PMASRs that have assessed the relationship between food and beverage groups and DRCDs. The objectives of this review were to aggregate PMASRs to obtain an overview of the associations between food and beverage groups (n = 17) and DRCDs (n = 10) and to establish new directions for future research needs. The present review of 304 PMASRs published between 1950 and 2013 confirmed that plant food groups are more protective than animal food groups against DRCDs. Within plant food groups, grain products are more protective than fruits and vegetables. Among animal food groups, dairy/milk products have a neutral effect on the risk of DRCDs, while red/processed meats tend to increase the risk. Among beverages, tea was the most protective and soft drinks the least protective against DRCDs. For two of the DRCDs examined, sarcopenia and kidney disease, no PMASR was found. Overweight/obesity, type 2 diabetes, and various types of cardiovascular disease and cancer accounted for 289 of the PMASRs. There is a crucial need to further study the associations between food and beverage groups and mental health, skeletal health, digestive diseases, liver diseases, kidney diseases, obesity, and type 2 diabetes. © 2014 International Life Sciences Institute.

  2. Is a schizo-obsessive subtype associated with cognitive impairment?: results from a large cross-sectional study in patients with psychosis and their unaffected relatives.

    NARCIS (Netherlands)

    Meijer, J.H.; Swets, M.; Keeman, S.; Nieman, D.H.; Meijer, C.J.; Kahn, R.S.; Linszen, D.H.; van Os, J.; Wiersma, D.; Bruggeman, R.; Cahn, W.; de Haan, L.; Krabbendam, L.; Myin-Germeys, I.

    2013-01-01

    The current study investigated whether candidate cognitive endophenotypes may be used to validate a schizo-obsessive subtype. Using within-subject random effect regression analyses and cross-trait cross-relative analyses, we evaluated the association between obsessive-compulsive symptoms (OCSs) and

  3. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

    DEFF Research Database (Denmark)

    Nielsen, Tenna Ruest Haarmark; Appel, Emil Vincent Rosenbaum; Svendstrup, Mathilde

    2017-01-01

    BackgroundHypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH......) and free thyroxine (fT4), respectively.ObjectiveThis study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity.MethodsGenome-wide association analyses of imputed genotype...... data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5-24.7]). Replication...

  4. Toward a panoramic perspective of the association between environmental factors and cardiovascular disease: An environment-wide association study from National Health and Nutrition Examination Survey 1999-2014.

    Science.gov (United States)

    Zhuang, Xiaodong; Guo, Yue; Ni, Ao; Yang, Daya; Liao, Lizhen; Zhang, Shaozhao; Zhou, Huimin; Sun, Xiuting; Wang, Lichun; Wang, Xueqin; Liao, Xinxue

    2018-06-04

    An environment-wide association study (EWAS) may be useful to comprehensively test and validate associations between environmental factors and cardiovascular disease (CVD) in an unbiased manner. Data from National Health and Nutrition Examination Survey (1999-2014) were randomly 50:50 spilt into training set and testing set. CVD was ascertained by a self-reported diagnosis of myocardial infarction, coronary heart disease or stroke. We performed multiple linear regression analyses associating 203 environmental factors and 132 clinical phenotypes with CVD in training set (false discovery rate multicollinearity elimination and variable importance ranking. Discriminative power of factors for CVD was calculated by area under the receiver operating characteristic (AUROC). Overall, 43,568 participants with 4084 (9.4%) CVD were included. After adjusting for age, sex, race, body mass index, blood pressure and socio-economic level, we identified 5 environmental variables and 19 clinical phenotypes associated with CVD in training and testing dataset. Top five factors in RF importance ranking were: waist, glucose, uric acid, and red cell distribution width and glycated hemoglobin. AUROC of the RF model was 0.816 (top 5 factors) and 0.819 (full model). Sensitivity analyses reveal no specific moderators of the associations. Our systematic evaluation provides new knowledge on the complex array of environmental correlates of CVD. These identified correlates may serve as a complementary approach to CVD risk assessment. Our findings need to be probed in further observational and interventional studies. Copyright © 2018. Published by Elsevier Ltd.

  5. Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study.

    Science.gov (United States)

    Andersen, Vibeke; Ernst, Anja; Sventoraityte, Jurgita; Kupcinskas, Limas; Jacobsen, Bent A; Krarup, Henrik B; Vogel, Ulla; Jonaitis, Laimas; Denapiene, Goda; Kiudelis, Gediminas; Balschun, Tobias; Franke, Andre

    2011-10-13

    Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).No SNP reached genome

  6. Genome-wide association study identifies novel locus for neuroticism and shows polygenic association with Major Depressive Disorder

    Science.gov (United States)

    de Moor, Marleen H.M.; van den Berg, Stéphanie M.; Verweij, Karin J.H.; Krueger, Robert F.; Luciano, Michelle; Vasquez, Alejandro Arias; Matteson, Lindsay K.; Derringer, Jaime; Esko, Tõnu; Amin, Najaf; Gordon, Scott D.; Hansell, Narelle K.; Hart, Amy B.; Seppälä, Ilkka; Huffman, Jennifer E.; Konte, Bettina; Lahti, Jari; Lee, Minyoung; Miller, Mike; Nutile, Teresa; Tanaka, Toshiko; Teumer, Alexander; Viktorin, Alexander; Wedenoja, Juho; Abecasis, Goncalo R.; Adkins, Daniel E.; Agrawal, Arpana; Allik, Jüri; Appel, Katja; Bigdeli, Timothy B.; Busonero, Fabio; Campbell, Harry; Costa, Paul T.; Smith, George Davey; Davies, Gail; de Wit, Harriet; Ding, Jun; Engelhardt, Barbara E.; Eriksson, Johan G.; Fedko, Iryna O.; Ferrucci, Luigi; Franke, Barbara; Giegling, Ina; Grucza, Richard; Hartmann, Annette M.; Heath, Andrew C.; Heinonen, Kati; Henders, Anjali K.; Homuth, Georg; Hottenga, Jouke-Jan; Janzing, Joost; Jokela, Markus; Karlsson, Robert; Kemp, John P.; Kirkpatrick, Matthew G.; Latvala, Antti; Lehtimäki, Terho; Liewald, David C.; Madden, Pamela A.F.; Magri, Chiara; Magnusson, Patrik K.E.; Marten, Jonathan; Maschio, Andrea; Medland, Sarah E.; Mihailov, Evelin; Milaneschi, Yuri; Montgomery, Grant W.; Nauck, Matthias; Ouwens, Klaasjan G.; Palotie, Aarno; Pettersson, Erik; Polasek, Ozren; Qian, Yong; Pulkki-Råback, Laura; Raitakari, Olli T.; Realo, Anu; Rose, Richard J.; Ruggiero, Daniela; Schmidt, Carsten O.; Slutske, Wendy S.; Sorice, Rossella; Starr, John M.; Pourcain, Beate St; Sutin, Angelina R.; Timpson, Nicholas J.; Trochet, Holly; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Wouda, Jasper; Wright, Margaret J.; Zgaga, Lina; Scotland, Generation; Porteous, David; Minelli, Alessandra; Palmer, Abraham A.; Rujescu, Dan; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Metspalu, Andres; Kaprio, Jaakko; Deary, Ian J.; Räikkönen, Katri; Wilson, James F.; Keltikangas-Järvinen, Liisa; Bierut, Laura J.; Hettema, John M.; Grabe, Hans J.; van Duijn, Cornelia M.; Evans, David M.; Schlessinger, David; Pedersen, Nancy L.; Terracciano, Antonio; McGue, Matt; Penninx, Brenda W.J.H.; Martin, Nicholas G.; Boomsma, Dorret I.

    2015-01-01

    Importance Neuroticism is a personality trait that is briefly defined by emotional instability. It is a robust genetic risk factor for Major Depressive Disorder (MDD) and other psychiatric disorders. Hence, neuroticism is an important phenotype for psychiatric genetics. The Genetics of Personality Consortium (GPC) has created a resource for genome-wide association analyses of personality traits in over 63,000 participants (including MDD cases). Objective To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association (GWA) results based on 1000Genomes imputation, to evaluate if common genetic variants as assessed by Single Nucleotide Polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability, and to examine whether SNPs that predict neuroticism also predict MDD. Setting 30 cohorts with genome-wide genotype, personality and MDD data from the GPC. Participants The study included 63,661 participants from 29 discovery cohorts and 9,786 participants from a replication cohort. Participants came from Europe, the United States or Australia. Main outcome measure(s) Neuroticism scores harmonized across all cohorts by Item Response Theory (IRT) analysis, and clinically assessed MDD case-control status. Results A genome-wide significant SNP was found in the MAGI1 gene (rs35855737; P=9.26 × 10−9 in the discovery meta-analysis, and P=2.38 × 10−8 in the meta-analysis of all 30 cohorts). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 of the discovery cohorts significantly predicted neuroticism in 2 independent cohorts. Importantly, polygenic scores also predicted MDD in these cohorts. Conclusions and relevance This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study

  7. Association between dietary nitrate and nitrite intake and sitespecific cancer risk: evidence from observational studies.

    Science.gov (United States)

    Xie, Li; Mo, Miao; Jia, Hui-Xun; Liang, Fei; Yuan, Jing; Zhu, Ji

    2016-08-30

    Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30th, 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted. Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers.

  8. 14C-analyses of calcite coatings in open fractures from the Klipperaas study site, Southern Sweden

    International Nuclear Information System (INIS)

    Possnert, G.; Tullborg, E.L.

    1989-11-01

    Carbonate samples from open fractures in crystalline rock from the Klipperaas study site have been analysed for their 14 C contents using accelerator mass spectrometry. This technique makes it possible to analyse very small carbonate samples (c. 1 mg C). The analyses show low but varying contents of 14 C. However, contamination by CO 2 have taken place affecting small samples more than others. Attempts have been made to quantify the contamination and thus evaluate the analyses of the fracture samples. The obtained low 14 C values can be due to: 1. An effective retention of 14 C by sorption/fractionation forcing 14 C onto the calcite surfaces in the near-surface zone which means that the 14 C contribution to the deeper levels is diminished or 2. the penetration depth of surface groundwater is very shallow. The former is suggested as more probable based on evaluations of the hydrochemical conditions and the fracture mineral studies. (10 figs., 3 tabs., 9 refs.) (authors)

  9. Association between Frequency of Consumption of Fruit, Vegetables, Nuts and Pulses and BMI: Analyses of the International Study of Asthma and Allergies in Childhood (ISAAC).

    Science.gov (United States)

    Wall, Clare R; Stewart, Alistair W; Hancox, Robert J; Murphy, Rinki; Braithwaite, Irene; Beasley, Richard; Mitchell, Edwin A

    2018-03-07

    Diets which emphasize intakes of plant-based foods are recommended to reduce disease risk and for promoting healthy weight. The aim of this study was to examine the association between fruit, vegetables, pulses and nut intake and body mass index (BMI) across countries in adolescents (13-14 years) and children (6-7 years). Data from the International Study of Asthma and Allergies in Childhood; 77,243 children's parents and 201,871 adolescents was used to examine the association between dietary intake (Food Frequency Questionnaire) and BMI using general linear models, adjusting for country gross national index. Adolescents who consumed fruit, vegetables, pulses and nuts three or more times a week had a lower BMI than the never or occasional group; eating nuts three or more times a week, was associated with a BMI value of 0.274 kg/m² lower than the never group ( p BMI of -0.079 kg/m². In this large global study, an inverse association was observed between BMI and the reported increasing intake of vegetables in 6-7 years old and fruit, vegetables, pulses and nuts in adolescents. This study supports current dietary recommendations which emphasize the consumption of vegetables, nut and pulses, although the effect sizes were small.

  10. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Science.gov (United States)

    Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

    2015-06-01

    study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure--or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications--may reduce AD risk.

  11. Association of airborne moisture-indicating microorganisms withbuilding-related symptoms and water damage in 100 U.S. office buildings:Analyses of the U.S. EPA BASE data

    Energy Technology Data Exchange (ETDEWEB)

    Mendell, Mark J.; Lei, Quanhong; Cozen, Myrna O.; Shendell, DerekG.; Macher, Janet M.; Tsai, Feng C.

    2003-10-01

    Metrics of culturable airborne microorganisms for either total organisms or suspected harmful subgroups have generally not been associated with symptoms among building occupants. However, the visible presence of moisture damage or mold in residences and other buildings has consistently been associated with respiratory symptoms and other health effects. This relationship is presumably caused by adverse but uncharacterized exposures to moisture-related microbiological growth. In order to assess this hypothesis, we studied relationships in U.S. office buildings between the prevalence of respiratory and irritant symptoms, the concentrations of airborne microorganisms that require moist surfaces on which to grow, and the presence of visible water damage. For these analyses we used data on buildings, indoor environments, and occupants collected from a representative sample of 100 U.S. office buildings in the U.S. Environmental Protection Agency's Building Assessment Survey and Evaluation (EPA BASE) study. We created 19 alternate metrics, using scales ranging from 3-10 units, that summarized the concentrations of airborne moisture-indicating microorganisms (AMIMOs) as indicators of moisture in buildings. Two were constructed to resemble a metric previously reported to be associated with lung function changes in building occupants; the others were based on another metric from the same group of Finnish researchers, concentration cutpoints from other studies, and professional judgment. We assessed three types of associations: between AMIMO metrics and symptoms in office workers, between evidence of water damage and symptoms, and between water damage and AMIMO metrics. We estimated (as odds ratios (ORs) with 95% confidence intervals) the unadjusted and adjusted associations between the 19 metrics and two types of weekly, work-related symptoms--lower respiratory and mucous membrane--using logistic regression models. Analyses used the original AMIMO metrics and were

  12. Temporomandibular disorders are differentially associated with headache diagnoses: a controlled study.

    Science.gov (United States)

    Gonçalves, Daniela A G; Camparis, Cinara M; Speciali, José G; Franco, Ana L; Castanharo, Sabrina M; Bigal, Marcelo E

    2011-09-01

    Temporomandibular disorders (TMDs) are considered to be comorbid with headaches. Earlier population studies have suggested that TMD may also be a risk factor for migraine progression. If that is true, TMD should be associated with specific headache syndromes (eg, migraine and chronic migraine), but not with headaches overall. Accordingly, our aim was to explore the relationship between TMD subtypes and severity with primary headaches in a controlled clinical study. The sample consisted of 300 individuals. TMDs were assessed using the Research Diagnostic Criteria for TMD, and primary headache was classified according to International Classification for Headache Disorders-2. Univariate and multivariate models assessed headache diagnoses and frequency as a function of the parameters of TMD. Relative to those without TMD, individuals with myofascial TMD were significantly more likely to have chronic daily headaches (CDHs) [relative risk (RR)=7.8; 95% confidence interval (CI), 3.1-19.6], migraine (RR=4.4; 95% CI, 1.7-11.7), and episodic tension-type headache (RR=4.4; 95% CI, 1.5-12.6). Grade of TMD pain was associated with increased odds of CDH (Pheadache (Pheadache frequency. In multivariate analyses, TMD was associated with migraine and CDH (P=0.001). Painful TMD (P=0.0034) and grade of TMD pain (Pheadache frequency. TMD, TMD subtypes, and TMD severity are independently associated with specific headache syndromes and with headache frequency. This differential association suggests that the presence of central facilitation of nociceptive inputs may be of importance, as positive association was observed only when muscular TMD pain was involved.

  13. A survey of the modern auto- and cross-spectral analyses for the purpose of tokamak study

    International Nuclear Information System (INIS)

    Iwama, N.

    1984-09-01

    The modern techniques of digital auto- and cross-spectral analyses are surveyed for the purpose of the CO 2 -laser scattering experiment on the microinstability and the associated anomalous diffusion in TFR tokamak. The outline of the practical procedures of spectral estimation and the underlying mathematical principles are described with emphasis on the comparison between the maximum entropy method and the conventional methods. The statistical properties of the spectral estimators are discussed and examined by experiments

  14. Methodological barriers to studying the association between the economic crisis and suicide in Spain.

    Science.gov (United States)

    Alvarez-Galvez, Javier; Salinas-Perez, Jose A; Rodero-Cosano, María Luisa; Salvador-Carulla, Luis

    2017-09-06

    The hypothetical relationship between economic recession and the increase in suicides in Spain is subject to various arguments. In addition to the inherent complexity of capturing and explaining the underlining mechanisms that could describe this causal link, different points of contention have been be identified. The period of this association and its possible starting points, the socioeconomic determinants that may explain the variation in suicide rate, and the data sources available are the main focus of controversy. The present study aims to identify the phases of association between different periods of economic recession and suicide rates, and compare the effect of different social determinants of health that have been mentioned in previous studies. We have used interrupted time series analyses to assess the impact of economic recession on national rates of suicide mortality provided by the Spanish Statistical Office (1980-2014). In an attempt to consider the factors that have affected the study of suicide in Spain, different data sources/periods, predictors, and regions in Spain were analysed. The analysis revealed a positive and significant relationship between the Great Recession and suicide rates during the second period of economic recession (2011-2014), while appeared to decrease during the first recession period. However, the first decreasing trend was not statistically significant in the global analysis of the evolution of monthly suicide rates for the entire country. Both unemployment and per capita GDP were positively related to suicide trends. Finally, the regional analysis demonstrates a similar pattern in different Spanish areas. Although previous studies have mentioned the double-dip in the suicide rate associated with the corresponding period of double recession, our study only identify a positive relationship during the second recession period. These results points out that the major impact of economic problems might have had a delayed effect

  15. Preterm Birth Associated With Group B Streptococcus Maternal Colonization Worldwide: Systematic Review and Meta-analyses.

    Science.gov (United States)

    Bianchi-Jassir, Fiorella; Seale, Anna C; Kohli-Lynch, Maya; Lawn, Joy E; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Heath, Paul T; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Saha, Samir K; Schrag, Stephanie; Sobanjo-Ter Meulen, Ajoke; Vekemans, Johan; Rubens, Craig E

    2017-11-06

    Preterm birth complications are the leading cause of deaths among children birth in order to inform estimates of the burden of GBS. We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on the association of preterm birth (birth with maternal GBS colonization to be 1.21 (95% confidence interval [CI], .99-1.48; P = .061) in cohort and cross-sectional studies, and the odds ratio to be 1.85 (95% CI, 1.24-2.77; P = .003) in case-control studies. Preterm birth was associated with GBS bacteriuria in cohort studies (RR, 1.98 [95% CI, 1.45-2.69]; P birth is associated with maternal GBS colonization, especially where there is evidence of ascending infection (bacteriuria). Several biases reduce the chance of detecting an effect. Equally, however, results, including evidence for the association, may be due to confounding, which is rarely addressed in studies. Assessment of any effect on preterm delivery should be included in future maternal GBS vaccine trials. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  16. CVD diamond Brewster window: feasibility study by FEM analyses

    Directory of Open Access Journals (Sweden)

    Vaccaro A.

    2012-09-01

    Full Text Available Chemical vapor deposition (CVD diamond windows are a crucial component in heating and current drive (H&CD applications. In order to minimize the amount of reflected power from the diamond disc, its thickness must match the desired beam wavelength, thus proper targeting of the plasma requires movable beam reflectors. This is the case, for instance, of the ITER electron cyclotron H&CD system. However, looking at DEMO, the higher heat loads and neutron fluxes could make the use of movable parts close to the plasma difficult. The issue might be solved by using gyrotrons able to tune the beam frequency to the desired resonance, but this concept requires transmission windows that work in a given frequency range, such as the Brewster window. It consists of a CVD diamond disc brazed to two copper cuffs at the Brewster angle. The brazing process is carried out at about 800°C and then the temperature is decreased down to room temperature. Diamond and copper have very different thermal expansion coefficients, therefore high stresses build up during the cool down phase that might lead to failure of the disc. Considering also the complex geometry of the window with the skewed position of the disc, analyses are required in the first place to check its feasibility. The cool down phase was simulated by FEM structural analyses for several geometric and constraint configurations of the window. A study of indirect cooling of the window by water was also performed considering a HE11 mode beam. The results are here reported.

  17. Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

    Directory of Open Access Journals (Sweden)

    Sandosh Padmanabhan

    2010-10-01

    Full Text Available Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹. The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91], reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027. In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003. In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

  18. Electroencephalographic power and coherence analyses suggest altered brain function in abstinent male heroin-dependent patients

    NARCIS (Netherlands)

    Franken, Ingmar H. A.; Stam, Cornelis J.; Hendriks, Vincent M.; van den Brink, Wim

    2004-01-01

    Previous studies have shown that drug abuse is associated with altered brain function. However, studies of heroin abuse-related brain dysfunctions are scarce. Electroencephalographic ( EEG) power and coherence analyses are two important tools for examining the effects of drugs on brain function. In

  19. Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

    Science.gov (United States)

    Demirkan, A; Lahti, J; Direk, N; Viktorin, A; Lunetta, K L; Terracciano, A; Nalls, M A; Tanaka, T; Hek, K; Fornage, M; Wellmann, J; Cornelis, M C; Ollila, H M; Yu, L; Smith, J A; Pilling, L C; Isaacs, A; Palotie, A; Zhuang, W V; Zonderman, A; Faul, J D; Sutin, A; Meirelles, O; Mulas, A; Hofman, A; Uitterlinden, A; Rivadeneira, F; Perola, M; Zhao, W; Salomaa, V; Yaffe, K; Luik, A I; Liu, Y; Ding, J; Lichtenstein, P; Landén, M; Widen, E; Weir, D R; Llewellyn, D J; Murray, A; Kardia, S L R; Eriksson, J G; Koenen, K; Magnusson, P K E; Ferrucci, L; Mosley, T H; Cucca, F; Oostra, B A; Bennett, D A; Paunio, T; Berger, K; Harris, T B; Pedersen, N L; Murabito, J M; Tiemeier, H; van Duijn, C M; Räikkönen, K

    2016-06-01

    Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

  20. Study of the factors associated with substance use in adolescence using Association Rules.

    Science.gov (United States)

    García, Elena Gervilla; Blasco, Berta Cajal; López, Rafael Jiménez; Pol, Alfonso Palmer

    2010-01-01

    The aim of this study is to analyse the factors related to the use of addictive substances in adolescence using association rules, descriptive tools included in Data Mining. Thus, we have a database referring to the consumption of addictive substances in adolescence, and use the free distribution program in the R arules package (version 2.10.0). The sample was made up of 9,300 students between the ages of 14 and 18 (47.1% boys and 52.9% girls) with an average age of 15.6 (SE=1.2). The adolescents answered an anonymous questionnaire on personal, family and environmental risk factors related to substance use. The best rules obtained with regard to substance use relate the consumption of alcohol to perceived parenting style and peer consumption (confidence = 0.8528), the use of tobacco (smoking), cannabis and cocaine to perceived parental action and illegal behaviour (confidence = 0.8032, 0.8718 and 1.0000, respectively), and the use of ecstasy to peer consumption (confidence = 1.0000). In general, the association rules show in a simple manner the relationship between certain patterns of perceived parental action, behaviours that deviate from social behavioural norms, peer consumption and the use of different legal and illegal drugs of abuse in adolescence. The implications of the results obtained are described, together with the usefulness of this new methodology of analysis.

  1. Grey literature in meta-analyses.

    Science.gov (United States)

    Conn, Vicki S; Valentine, Jeffrey C; Cooper, Harris M; Rantz, Marilyn J

    2003-01-01

    In meta-analysis, researchers combine the results of individual studies to arrive at cumulative conclusions. Meta-analysts sometimes include "grey literature" in their evidential base, which includes unpublished studies and studies published outside widely available journals. Because grey literature is a source of data that might not employ peer review, critics have questioned the validity of its data and the results of meta-analyses that include it. To examine evidence regarding whether grey literature should be included in meta-analyses and strategies to manage grey literature in quantitative synthesis. This article reviews evidence on whether the results of studies published in peer-reviewed journals are representative of results from broader samplings of research on a topic as a rationale for inclusion of grey literature. Strategies to enhance access to grey literature are addressed. The most consistent and robust difference between published and grey literature is that published research is more likely to contain results that are statistically significant. Effect size estimates of published research are about one-third larger than those of unpublished studies. Unfunded and small sample studies are less likely to be published. Yet, importantly, methodological rigor does not differ between published and grey literature. Meta-analyses that exclude grey literature likely (a) over-represent studies with statistically significant findings, (b) inflate effect size estimates, and (c) provide less precise effect size estimates than meta-analyses including grey literature. Meta-analyses should include grey literature to fully reflect the existing evidential base and should assess the impact of methodological variations through moderator analysis.

  2. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Kottgen, A.; Albrecht, E.; Teumer, A.; Vitart, V.; Krumsiek, J.; Hundertmark, C.; Pistis, G.; Ruggiero, D.; O'Seaghdha, C.M.; Haller, T.; Yang, Q.; Johnson, A.D.; Kutalik, Z.; Smith, A.V.; Shi, J.L.; Struchalin, M.; Middelberg, R.P.S.; Brown, M.J.; Gaffo, A.L.; Pirastu, N.; Li, G.; Hayward, C.; Zemunik, T.; Huffman, J.; Yengo, L.; Zhao, J.H.; Demirkan, A.; Feitosa, M.F.; Liu, X.; Malerba, G.; Lopez, L.M.; van der Harst, P.; Li, X.Z.; Kleber, M.E.; Hicks, A.A.; Nolte, I.M.; Johansson, A.; Murgia, F.; Wild, S.H.; Bakker, S.J.L.; Peden, J.F.; Dehghan, A.; Steri, M.; Tenesa, A.; Lagou, V.; Salo, P.; Mangino, M.; Rose, L.M.; Lehtimaki, T.; Woodward, O.M.; Okada, Y.; Tin, A.; Muller, C.; Oldmeadow, C.; Putku, M.; Czamara, D.; Kraft, P.; Frogheri, L.; Thun, G.A.; Grotevendt, A.; Gislason, G.K.; Harris, T.B.; Launer, L.J.; McArdle, P.; Shuldiner, A.R.; Boerwinkle, E.; Coresh, J.; Schmidt, H.; Schallert, M.; Martin, N.G.; Montgomery, G.W.; Kubo, M.; Nakamura, Y.; Tanaka, T.; Munroe, P.B.; Samani, N.J.; Jacobs, D.R.; Liu, K.; d'Adamo, P.; Ulivi, S.; Rotter, J.I.; Psaty, B.M.; Vollenweider, P.; Waeber, G.; Campbell, S.; Devuyst, O.; Navarro, P.; Kolcic, I.; Hastie, N.; Balkau, B.; Froguel, P.; Esko, T.; Salumets, A.; Khaw, K.T.; Langenberg, C.; Wareham, N.J.; Isaacs, A.; Kraja, A.; Zhang, Q.Y.; Penninx, B.W.J.H.; Smit, J.H.; Bochud, M.; Gieger, C.

    2013-01-01

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with

  3. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    NARCIS (Netherlands)

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O'Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Bakker, Stephan J L; Lagou, Vasiliki; Bruinenberg, Marcel; Stolk, Ronald P; Penninx, Brenda W; Mateo Leach, Irene; van Gilst, Wiek H; Hillege, Hans L; Wolffenbuttel, Bruce H R; Snieder, Harold; Navis, Gerjan

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with

  4. A case study of discordant overlapping meta-analyses: vitamin d supplements and fracture.

    Directory of Open Access Journals (Sweden)

    Mark J Bolland

    Full Text Available BACKGROUND: Overlapping meta-analyses on the same topic are now very common, and discordant results often occur. To explore why discordant results arise, we examined a common topic for overlapping meta-analyses- vitamin D supplements and fracture. METHODS AND FINDINGS: We identified 24 meta-analyses of vitamin D (with or without calcium and fracture in a PubMed search in October 2013, and analysed a sample of 7 meta-analyses in the highest ranking general medicine journals. We used the AMSTAR tool to assess the quality of the meta-analyses, and compared their methodologies, analytic techniques and results. Applying the AMSTAR tool suggested the meta-analyses were generally of high quality. Despite this, there were important differences in trial selection, data extraction, and analytical methods that were only apparent after detailed assessment. 25 trials were included in at least one meta-analysis. Four meta-analyses included all eligible trials according to the stated inclusion and exclusion criteria, but the other 3 meta-analyses "missed" between 3 and 8 trials, and 2 meta-analyses included apparently ineligible trials. The relative risks used for individual trials differed between meta-analyses for total fracture in 10 of 15 trials, and for hip fracture in 6 of 12 trials, because of different outcome definitions and analytic approaches. The majority of differences (11/16 led to more favourable estimates of vitamin D efficacy compared to estimates derived from unadjusted intention-to-treat analyses using all randomised participants. The conclusions of the meta-analyses were discordant, ranging from strong statements that vitamin D prevents fractures to equally strong statements that vitamin D without calcium does not prevent fractures. CONCLUSIONS: Substantial differences in trial selection, outcome definition and analytic methods between overlapping meta-analyses led to discordant estimates of the efficacy of vitamin D for fracture prevention

  5. Change in organizational justice as a predictor of insomnia symptoms: longitudinal study analysing observational data as a non-randomized pseudo-trial.

    Science.gov (United States)

    Lallukka, Tea; Halonen, Jaana I; Sivertsen, Børge; Pentti, Jaana; Stenholm, Sari; Virtanen, Marianna; Salo, Paula; Oksanen, Tuula; Elovainio, Marko; Vahtera, Jussi; Kivimäki, Mika

    2017-08-01

    Despite injustice at the workplace being a potential source of sleep problems, longitudinal evidence remains scarce. We examined whether changes in perceived organizational justice predicted changes in insomnia symptoms. Data on 24 287 Finnish public sector employees (82% women), from three consecutive survey waves between 2000 and 2012, were treated as 'pseudo-trials'. Thus, the analysis of unfavourable changes in organizational justice included participants without insomnia symptoms in Waves 1 and 2, with high organizational justice in Wave 1 and high or low justice in Wave 2 (N = 6307). In the analyses of favourable changes in justice, participants had insomnia symptoms in Waves 1 and 2, low justice in Wave 1 and high or low justice in Wave 2 (N = 2903). In both analyses, the outcome was insomnia symptoms in Wave 3. We used generalized estimating equation models to analyse the data. After adjusting for social and health-related covariates in Wave 1, unfavourable changes in relational organizational justice (i.e. fairness of managerial behaviours) were associated with increased odds of developing insomnia symptoms [odds ratio = 1.15; 95% confidence interval (CI) 1.02-1.30]. A favourable change in relational organizational justice was associated with lower odds of persistent insomnia symptoms (odds ratio = 0.83; 95% CI 0.71-0.96). Changes in procedural justice (i.e. the fairness of decision-making procedures) were not associated with insomnia symptoms. These data suggest that changes in perceived relational justice may affect employees' sleep quality. Decreases in the fairness of managerial behaviours were linked to increases in insomnia symptoms, whereas rises in fairness were associated with reduced insomnia symptoms. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

  6. Evaluation of European Schizophrenia GWAS Loci in Asian Populations via Comprehensive Meta-Analyses.

    Science.gov (United States)

    Xiao, Xiao; Luo, Xiong-Jian; Chang, Hong; Liu, Zichao; Li, Ming

    2017-08-01

    Schizophrenia is a severe and highly heritable neuropsychiatric disorder. Recent genetic analyses including genome-wide association studies (GWAS) have implicated multiple genome-wide significant variants for schizophrenia among European populations. However, many of these risk variants were not largely validated in other populations of different ancestry such as Asians. To validate whether these European GWAS significant loci are associated with schizophrenia in Asian populations, we conducted a systematic literature search and meta-analyses on 19 single nucleotide polymorphisms (SNPs) in Asian populations by combining all available case-control and family-based samples, including up to 30,000 individuals. We employed classical fixed (or random) effects inverse variance weighted methods to calculate summary odds ratios (ORs) and 95 % confidence intervals (CIs). Among the 19 GWAS loci, we replicated the risk associations of nine markers (e.g., SNPs at VRK2, ITIH3/4, NDST3, NOTCH4) surpassing significance level (two-tailed P Asian replication samples and initial European GWAS findings, and the successful replications of these GWAS loci in a different ethnic group provide stronger evidence for their clinical associations with schizophrenia. Further studies, focusing on the molecular mechanisms of these GWAS significant loci, will become increasingly important for understanding of the pathogenesis to schizophrenia.

  7. Using trajectory analyses to refine phenotype for genetic association: conduct problems and the serotonin transporter (5HTTLPR).

    Science.gov (United States)

    Sakai, Joseph T; Boardman, Jason D; Gelhorn, Heather L; Smolen, Andrew; Corley, Robin P; Huizinga, David; Menard, Scott; Hewitt, John K; Stallings, Michael C

    2010-10-01

    Conduct disorder is a serious, relatively common disorder of childhood and adolescence. Findings from genetic association studies searching for genetic determinants of the liability toward such behaviors have been inconsistent. One possible explanation for differential results is that most studies define phenotype from a single assessment; for many adolescents conduct problems decrease in severity over time, whereas for others such behaviors persist. Therefore, longitudinal datasets offer the opportunity to refine phenotype. We used Caucasians that were first assessed during adolescence from the National Youth Survey Family Study. Nine waves of data were used to create latent growth trajectories and test for associations between trajectory class and 5HTTLPR genotype. For the full sample, 5HTTLPR was not associated with conduct problem phenotypes. However, the short (s) allele was associated with chronic conduct problems in females; a nominally significant sex by 5HTTLPR genotype interaction was noted. Longitudinal studies provide unique opportunities for phenotypic refinement and such techniques, with large samples, may be useful for phenotypic definition with other study designs, such as whole genome association studies.

  8. Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure

    DEFF Research Database (Denmark)

    Winckelmans, Ellen; Nawrot, Tim S.; Tsamou, Maria

    2017-01-01

    validation cohort (n = 169, 55.6% women). Results: Overrepresentation analyses revealed significant pathways (p-value transport chain (ETC) for medium-term exposure in women. For men, medium-term PM10....... Conclusions: In this exploratory study, we identified mitochondrial genes and pathways associated with particulate air pollution indicating upregulation of energy producing pathways as a potential mechanism to compensate for PM-induced mitochondrial damage....

  9. No association between nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow: a cross-sectional general population study

    DEFF Research Database (Denmark)

    Thyssen, J P; Linneberg, A; Menné, T

    2010-01-01

    dermatitis and nickel in make-up products remains controversial. OBJECTIVE: This cross-sectional patch test study investigated whether the frequency of self-reported cosmetic dermatitis from mascara or eye shadow use was higher among nickel allergic Danish women than women without nickel allergy. METHODS......: In 2006, a total of 1843 18-69 year old women completed a postal questionnaire including questions on cosmetic dermatitis and were patch tested with nickel sulphate. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs......). RESULTS: The prevalence of nickel allergy was similar among women who reported cosmetic dermatitis from eye shadow or mascara and among women who did not report such symptoms. Cosmetic dermatitis was positively associated with self-reported atopic dermatitis and age. CONCLUSION: Overall, no association...

  10. Models and analyses for inertial-confinement fusion-reactor studies

    International Nuclear Information System (INIS)

    Bohachevsky, I.O.

    1981-05-01

    This report describes models and analyses devised at Los Alamos National Laboratory to determine the technical characteristics of different inertial confinement fusion (ICF) reactor elements required for component integration into a functional unit. We emphasize the generic properties of the different elements rather than specific designs. The topics discussed are general ICF reactor design considerations; reactor cavity phenomena, including the restoration of interpulse ambient conditions; first-wall temperature increases and material losses; reactor neutronics and hydrodynamic blanket response to neutron energy deposition; and analyses of loads and stresses in the reactor vessel walls, including remarks about the generation and propagation of very short wavelength stress waves. A discussion of analytic approaches useful in integrations and optimizations of ICF reactor systems concludes the report

  11. Energy and exergy analyses of electrolytic hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, M A [Ryerson Polytechnic Univ., Toronto, ON (Canada). Dept. of Mechanical Engineering

    1995-07-01

    The thermodynamic performance is investigated of a water-electrolysis process for producing hydrogen, based on current-technology equipment. Both energy and exergy analyses are used. Three cases are considered in which the principal driving energy inputs are (i) electricity, (ii) the high-temperature heat used to generate the electricity, and (iii) the heat source used to produce the high-temperature heat. The nature of the heat source (e.g.) fossil fuel, nuclear fuel, solar energy, (etc.) is left as general as possible. The analyses indicate that, when the main driving input is the hypothetical heat source, the principal thermodynamic losses are associated with water splitting, electricity generation and heat production; the losses are mainly due to the irreversibilities associated with converting a heat source to heat, and heat transfer across large temperature differences. The losses associated with the waste heat in used cooling water, because of its low quality, are not as significant as energy analysis indicates. (Author)

  12. Shotgun pyrosequencing metagenomic analyses of dusts from swine confinement and grain facilities.

    Science.gov (United States)

    Boissy, Robert J; Romberger, Debra J; Roughead, William A; Weissenburger-Moser, Lisa; Poole, Jill A; LeVan, Tricia D

    2014-01-01

    Inhalation of agricultural dusts causes inflammatory reactions and symptoms such as headache, fever, and malaise, which can progress to chronic airway inflammation and associated diseases, e.g. asthma, chronic bronchitis, chronic obstructive pulmonary disease, and hypersensitivity pneumonitis. Although in many agricultural environments feed particles are the major constituent of these dusts, the inflammatory responses that they provoke are likely attributable to particle-associated bacteria, archaebacteria, fungi, and viruses. In this study, we performed shotgun pyrosequencing metagenomic analyses of DNA from dusts from swine confinement facilities or grain elevators, with comparisons to dusts from pet-free households. DNA sequence alignment showed that 19% or 62% of shotgun pyrosequencing metagenomic DNA sequence reads from swine facility or household dusts, respectively, were of swine or human origin, respectively. In contrast only 2% of such reads from grain elevator dust were of mammalian origin. These metagenomic shotgun reads of mammalian origin were excluded from our analyses of agricultural dust microbiota. The ten most prevalent bacterial taxa identified in swine facility compared to grain elevator or household dust were comprised of 75%, 16%, and 42% gram-positive organisms, respectively. Four of the top five swine facility dust genera were assignable (Clostridium, Lactobacillus, Ruminococcus, and Eubacterium, ranging from 4% to 19% relative abundance). The relative abundances of these four genera were lower in dust from grain elevators or pet-free households. These analyses also highlighted the predominance in swine facility dust of Firmicutes (70%) at the phylum level, Clostridia (44%) at the Class level, and Clostridiales at the Order level (41%). In summary, shotgun pyrosequencing metagenomic analyses of agricultural dusts show that they differ qualitatively and quantitatively at the level of microbial taxa present, and that the bioinformatic analyses

  13. Shotgun pyrosequencing metagenomic analyses of dusts from swine confinement and grain facilities.

    Directory of Open Access Journals (Sweden)

    Robert J Boissy

    Full Text Available Inhalation of agricultural dusts causes inflammatory reactions and symptoms such as headache, fever, and malaise, which can progress to chronic airway inflammation and associated diseases, e.g. asthma, chronic bronchitis, chronic obstructive pulmonary disease, and hypersensitivity pneumonitis. Although in many agricultural environments feed particles are the major constituent of these dusts, the inflammatory responses that they provoke are likely attributable to particle-associated bacteria, archaebacteria, fungi, and viruses. In this study, we performed shotgun pyrosequencing metagenomic analyses of DNA from dusts from swine confinement facilities or grain elevators, with comparisons to dusts from pet-free households. DNA sequence alignment showed that 19% or 62% of shotgun pyrosequencing metagenomic DNA sequence reads from swine facility or household dusts, respectively, were of swine or human origin, respectively. In contrast only 2% of such reads from grain elevator dust were of mammalian origin. These metagenomic shotgun reads of mammalian origin were excluded from our analyses of agricultural dust microbiota. The ten most prevalent bacterial taxa identified in swine facility compared to grain elevator or household dust were comprised of 75%, 16%, and 42% gram-positive organisms, respectively. Four of the top five swine facility dust genera were assignable (Clostridium, Lactobacillus, Ruminococcus, and Eubacterium, ranging from 4% to 19% relative abundance. The relative abundances of these four genera were lower in dust from grain elevators or pet-free households. These analyses also highlighted the predominance in swine facility dust of Firmicutes (70% at the phylum level, Clostridia (44% at the Class level, and Clostridiales at the Order level (41%. In summary, shotgun pyrosequencing metagenomic analyses of agricultural dusts show that they differ qualitatively and quantitatively at the level of microbial taxa present, and that the

  14. Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study

    Science.gov (United States)

    Alonso-Perez, Elisa; Suarez-Gestal, Marian; Calaza, Manuel; Ordi-Ros, Josep; Balada, Eva; Bijl, Marc; Papasteriades, Chryssa; Carreira, Patricia; Skopouli, Fotini N.; Witte, Torsten; Endreffy, Emöke; Marchini, Maurizio; Migliaresi, Sergio; Sebastiani, Gian Domenico; Santos, Maria Jose; Suarez, Ana; Blanco, Francisco J.; Barizzone, Nadia; Pullmann, Rudolf; Ruzickova, Sarka; Lauwerys, Bernard R.; Gomez-Reino, Juan J.; Gonzalez, Antonio

    2012-01-01

    Introduction Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. Methods European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. Results There were three new associations: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30, Pcorr = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. Conclusion Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component. PMID:23049788

  15. Atherogenic index of plasma is a novel and better biomarker associated with obesity: a population-based cross-sectional study in China.

    Science.gov (United States)

    Zhu, Xiaowei; Yu, Lugang; Zhou, Hui; Ma, Qinhua; Zhou, Xiaohua; Lei, Ting; Hu, Jiarong; Xu, Wenxin; Yi, Nengjun; Lei, Shufeng

    2018-03-05

    Atherogenic index of plasma (AIP) has been reported to be associated with cardiovascular diseases. However no study has yet systematically evaluated the association between AIP and obesity and its advantage in obesity prediction compared with conventional lipid components. A total of 6465 participants aged over 30 years were included in this study. Blood lipid components including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured, and AIP was calculated as log 10 (TG/HDL-C). Pearson correlation analyses, multivariable logistic analyses and predictive analyses were used to evaluate the association and discrimination ability between AIP, four conventional lipid profiles and obesity. Subjects in the higher quartiles of AIP all had a significantly increased risk of obesity compared with those in the lowest quartile (P for trend< 0.01). AIP showed a stronger association with obesity than the conventional lipid components as the pearson coefficient reached up to 0.372 and the adjusted odds ratio was 5.55. Using AIP rather than HDL-C and TG significantly improved risk prediction for obesity (AUC improvement = 0.011, P = 0.011; Continuous net reclassification index = 29.55%, P < 0.01; Category net reclassification index = 6.06%; Integrated discrimination improvement = 0.68%, P < 0.01). Higher AIP level was positively and strongly associated with obesity. AIP is a novel and better biomarker associated with obesity. Controlling the AIP level would be more helpful for the prevention of obesity.

  16. Associations of socioeconomic factors with inadequate dietary intake in food aid users in France (the ABENA study 2004–2005)

    OpenAIRE

    Méjean, Caroline; Deschamps, V.; Bellin-Lestienne, C.; Oleko, A.; Darmon, Nicole; Serge, H.; Katia, C.

    2010-01-01

    Background/Objectives: Few studies in Europe have examined the relationship of sociodemographic and economic factors with diet in deprived populations. We analysed the association between socioeconomic characteristics and consumption of different food groups in food aid users. Subjects/Methods: A cross-sectional study was conducted among food aid users in four urban French zones (n=1664). Associations of sociodemographic and economic factors and food aid use with frequency of consumption of t...

  17. Positive associations between consumerism and tobacco and alcohol use in early adolescence: cross-sectional study

    Science.gov (United States)

    Sweeting, Helen N; Bhaskar, Abita; Hunt, Kate

    2012-01-01

    Background There is concern about the negative impact of modern consumer culture on young people's mental health, but very few studies have investigated associations with substance use. In those which have, positive associations have been attributed to attempts to satisfy the unmet needs of more materialistic individuals. Objectives This study examines associations between different dimensions of consumerism and tobacco and alcohol use among Scottish early adolescents. Design Cross-sectional study. Setting and participants 2937 (92% of those eligible) secondary school pupils (ages 12–14) completed questionnaires in examination conditions. Analyses were restricted to those with complete data on all relevant variables (N=2736 smoking; N=2737 drinking). Measures Dependent variables comprised ever smoking and current drinking. Measures of consumerism comprised number of ‘premium’ (range 0–7) and ‘standard’ (range 0–5) material possessions and three Consumer Involvement subscales, ‘dissatisfaction’, ‘consumer orientation’ and ‘brand awareness’ (each range 3–12). Analyses also included school-year group and family affluence. Results Ever smoking and current drinking were both more prevalent among adolescents with more ‘premium’ and ‘standard’ material possessions, greater consumer ‘dissatisfaction’ and ‘brand awareness’ (mutually adjusted analyses including school-year group and family affluence). The strongest relationships occurred for ‘brand awareness’: for each unit increase in ‘brand awareness’ the ORs (95% CI) of ever smoking were 1.17 (1.08 to 1.26) and 1.23 (1.14 to 1.33) in males and females, respectively; and those for drinking were 1.15 (1.08 to 1.23) and 1.21 (1.13 to 1.30). ‘Brand awareness’ had an equal or stronger relationship with both smoking and drinking than did family affluence. Conclusions These results suggest aassociations between consumerism and both smoking and drinking might arise because

  18. Volunteering is associated with increased survival in able-bodied participants of the English Longitudinal Study of Ageing.

    Science.gov (United States)

    Rogers, Nina Trivedy; Demakakos, Panayotes; Taylor, Mark Steven; Steptoe, Andrew; Hamer, Mark; Shankar, Aparna

    2016-06-01

    Volunteering has been linked to reduced mortality in older adults, but the mechanisms explaining this effect remain unclear. This study investigated whether volunteering is associated with increased survival in participants of the English Longitudinal Study of Ageing and whether differences in survival are modified by functional disabilities. A multivariate Cox Proportional Hazards model was used to estimate the association of volunteering with survival over a period of 10.9 years in 10 324 participants, while controlling for selected confounders. To investigate effect modification by disability, the analyses were repeated in participants with and without self-reported functional disabilities. Volunteering was associated with a reduced probability of death from all causes in univariate analyses (HR=0.65, CI 0.58 to 0.73, pvolunteers had significantly increased survival compared with able-bodied non-volunteers (HR=0.81, 95% CI 0.69 to 0.95, p=0.009). There was no significant survival advantage among disabled volunteers, compared with disabled non-volunteers (HR=1.06, CI 0.88 to 1.29, p=0.53). Volunteering is associated with reduced mortality in older adults in England, but this effect appears to be limited to volunteers who report no disabilities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. Genome-Wide Study of Percent Emphysema on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study

    Science.gov (United States)

    Manichaikul, Ani; Hoffman, Eric A.; Smolonska, Joanna; Gao, Wei; Cho, Michael H.; Baumhauer, Heather; Budoff, Matthew; Austin, John H. M.; Washko, George R.; Carr, J. Jeffrey; Kaufman, Joel D.; Pottinger, Tess; Powell, Charles A.; Wijmenga, Cisca; Zanen, Pieter; Groen, Harry J. M.; Postma, Dirkje S.; Wanner, Adam; Rouhani, Farshid N.; Brantly, Mark L.; Powell, Rhea; Smith, Benjamin M.; Rabinowitz, Dan; Raffel, Leslie J.; Hinckley Stukovsky, Karen D.; Crapo, James D.; Beaty, Terri H.; Hokanson, John E.; Silverman, Edwin K.; Dupuis, Josée; O’Connor, George T.; Boezen, H. Marike; Rich, Stephen S.

    2014-01-01

    Rationale: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering. Objectives: To complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States. Methods: We determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than −950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity. Measurements and Main Results: Among 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10−8) and PPT2 (rs10947233; P = 3.2 × 10−8), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase–related gene MAN2B1 (rs10411619; P = 1.1 × 10−9; minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10−10; MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10−8; MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase–related gene, MAN1C1 (rs12130495; P = 9.9 × 10−6; MAF, 13.3%) was associated with percent emphysema. Conclusions: Our results suggest that some genes previously identified as

  20. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.

    Science.gov (United States)

    Day, Felix R; Thompson, Deborah J; Helgason, Hannes; Chasman, Daniel I; Finucane, Hilary; Sulem, Patrick; Ruth, Katherine S; Whalen, Sean; Sarkar, Abhishek K; Albrecht, Eva; Altmaier, Elisabeth; Amini, Marzyeh; Barbieri, Caterina M; Boutin, Thibaud; Campbell, Archie; Demerath, Ellen; Giri, Ayush; He, Chunyan; Hottenga, Jouke J; Karlsson, Robert; Kolcic, Ivana; Loh, Po-Ru; Lunetta, Kathryn L; Mangino, Massimo; Marco, Brumat; McMahon, George; Medland, Sarah E; Nolte, Ilja M; Noordam, Raymond; Nutile, Teresa; Paternoster, Lavinia; Perjakova, Natalia; Porcu, Eleonora; Rose, Lynda M; Schraut, Katharina E; Segrè, Ayellet V; Smith, Albert V; Stolk, Lisette; Teumer, Alexander; Andrulis, Irene L; Bandinelli, Stefania; Beckmann, Matthias W; Benitez, Javier; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bojesen, Stig E; Bolla, Manjeet K; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Broer, Linda; Brüning, Thomas; Buring, Julie E; Campbell, Harry; Catamo, Eulalia; Chanock, Stephen; Chenevix-Trench, Georgia; Corre, Tanguy; Couch, Fergus J; Cousminer, Diana L; Cox, Angela; Crisponi, Laura; Czene, Kamila; Davey Smith, George; de Geus, Eco J C N; de Mutsert, Renée; De Vivo, Immaculata; Dennis, Joe; Devilee, Peter; Dos-Santos-Silva, Isabel; Dunning, Alison M; Eriksson, Johan G; Fasching, Peter A; Fernández-Rhodes, Lindsay; Ferrucci, Luigi; Flesch-Janys, Dieter; Franke, Lude; Gabrielson, Marike; Gandin, Ilaria; Giles, Graham G; Grallert, Harald; Gudbjartsson, Daniel F; Guénel, Pascal; Hall, Per; Hallberg, Emily; Hamann, Ute; Harris, Tamara B; Hartman, Catharina A; Heiss, Gerardo; Hooning, Maartje J; Hopper, John L; Hu, Frank; Hunter, David J; Ikram, M Arfan; Im, Hae Kyung; Järvelin, Marjo-Riitta; Joshi, Peter K; Karasik, David; Kellis, Manolis; Kutalik, Zoltan; LaChance, Genevieve; Lambrechts, Diether; Langenberg, Claudia; Launer, Lenore J; Laven, Joop S E; Lenarduzzi, Stefania; Li, Jingmei; Lind, Penelope A; Lindstrom, Sara; Liu, YongMei; Luan, Jian'an; Mägi, Reedik; Mannermaa, Arto; Mbarek, Hamdi; McCarthy, Mark I; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Metspalu, Andres; Michailidou, Kyriaki; Milani, Lili; Milne, Roger L; Montgomery, Grant W; Mulligan, Anna M; Nalls, Mike A; Navarro, Pau; Nevanlinna, Heli; Nyholt, Dale R; Oldehinkel, Albertine J; O'Mara, Tracy A; Padmanabhan, Sandosh; Palotie, Aarno; Pedersen, Nancy; Peters, Annette; Peto, Julian; Pharoah, Paul D P; Pouta, Anneli; Radice, Paolo; Rahman, Iffat; Ring, Susan M; Robino, Antonietta; Rosendaal, Frits R; Rudan, Igor; Rueedi, Rico; Ruggiero, Daniela; Sala, Cinzia F; Schmidt, Marjanka K; Scott, Robert A; Shah, Mitul; Sorice, Rossella; Southey, Melissa C; Sovio, Ulla; Stampfer, Meir; Steri, Maristella; Strauch, Konstantin; Tanaka, Toshiko; Tikkanen, Emmi; Timpson, Nicholas J; Traglia, Michela; Truong, Thérèse; Tyrer, Jonathan P; Uitterlinden, André G; Edwards, Digna R Velez; Vitart, Veronique; Völker, Uwe; Vollenweider, Peter; Wang, Qin; Widen, Elisabeth; van Dijk, Ko Willems; Willemsen, Gonneke; Winqvist, Robert; Wolffenbuttel, Bruce H R; Zhao, Jing Hua; Zoledziewska, Magdalena; Zygmunt, Marek; Alizadeh, Behrooz Z; Boomsma, Dorret I; Ciullo, Marina; Cucca, Francesco; Esko, Tõnu; Franceschini, Nora; Gieger, Christian; Gudnason, Vilmundur; Hayward, Caroline; Kraft, Peter; Lawlor, Debbie A; Magnusson, Patrik K E; Martin, Nicholas G; Mook-Kanamori, Dennis O; Nohr, Ellen A; Polasek, Ozren; Porteous, David; Price, Alkes L; Ridker, Paul M; Snieder, Harold; Spector, Tim D; Stöckl, Doris; Toniolo, Daniela; Ulivi, Sheila; Visser, Jenny A; Völzke, Henry; Wareham, Nicholas J; Wilson, James F; Spurdle, Amanda B; Thorsteindottir, Unnur; Pollard, Katherine S; Easton, Douglas F; Tung, Joyce Y; Chang-Claude, Jenny; Hinds, David; Murray, Anna; Murabito, Joanne M; Stefansson, Kari; Ong, Ken K; Perry, John R B

    2017-06-01

    The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10 -8 ) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

  1. Analyses of non-fatal accidents in an opencast mine by logistic regression model - a case study.

    Science.gov (United States)

    Onder, Seyhan; Mutlu, Mert

    2017-09-01

    Accidents cause major damage for both workers and enterprises in the mining industry. To reduce the number of occupational accidents, these incidents should be properly registered and carefully analysed. This study efficiently examines the Aegean Lignite Enterprise (ELI) of Turkish Coal Enterprises (TKI) in Soma between 2006 and 2011, and opencast coal mine occupational accident records were used for statistical analyses. A total of 231 occupational accidents were analysed for this study. The accident records were categorized into seven groups: area, reason, occupation, part of body, age, shift hour and lost days. The SPSS package program was used in this study for logistic regression analyses, which predicted the probability of accidents resulting in greater or less than 3 lost workdays for non-fatal injuries. Social facilities-area of surface installations, workshops and opencast mining areas are the areas with the highest probability for accidents with greater than 3 lost workdays for non-fatal injuries, while the reasons with the highest probability for these types of accidents are transporting and manual handling. Additionally, the model was tested for such reported accidents that occurred in 2012 for the ELI in Soma and estimated the probability of exposure to accidents with lost workdays correctly by 70%.

  2. Remote sensing and spatial analysis based study for detecting deforestation and the associated drivers

    Science.gov (United States)

    El-Abbas, Mustafa M.; Csaplovics, Elmar; Deafalla, Taisser H.

    2013-10-01

    Nowadays, remote-sensing technologies are becoming increasingly interlinked to the issue of deforestation. They offer a systematized and objective strategy to document, understand and simulate the deforestation process and its associated causes. In this context, the main goal of this study, conducted in the Blue Nile region of Sudan, in which most of the natural habitats were dramatically destroyed, was to develop spatial methodologies to assess the deforestation dynamics and its associated factors. To achieve that, optical multispectral satellite scenes (i.e., ASTER and LANDSAT) integrated with field survey in addition to multiple data sources were used for the analyses. Spatiotemporal Object Based Image Analysis (STOBIA) was applied to assess the change dynamics within the period of study. Broadly, the above mentioned analyses include; Object Based (OB) classifications, post-classification change detection, data fusion, information extraction and spatial analysis. Hierarchical multi-scale segmentation thresholds were applied and each class was delimited with semantic meanings by a set of rules associated with membership functions. Consequently, the fused multi-temporal data were introduced to create detailed objects of change classes from the input LU/LC classes. The dynamic changes were quantified and spatially located as well as the spatial and contextual relations from adjacent areas were analyzed. The main finding of the present study is that, the forest areas were drastically decreased, while the agrarian structure in conversion of forest into agricultural fields and grassland was the main force of deforestation. In contrast, the capability of the area to recover was clearly observed. The study concludes with a brief assessment of an 'oriented' framework, focused on the alarming areas where serious dynamics are located and where urgent plans and interventions are most critical, guided with potential solutions based on the identified driving forces.

  3. Metagenomic analyses of bacteria on human hairs: a qualitative assessment for applications in forensic science.

    Science.gov (United States)

    Tridico, Silvana R; Murray, Dáithí C; Addison, Jayne; Kirkbride, Kenneth P; Bunce, Michael

    2014-01-01

    Mammalian hairs are one of the most ubiquitous types of trace evidence collected in the course of forensic investigations. However, hairs that are naturally shed or that lack roots are problematic substrates for DNA profiling; these hair types often contain insufficient nuclear DNA to yield short tandem repeat (STR) profiles. Whilst there have been a number of initial investigations evaluating the value of metagenomics analyses for forensic applications (e.g. examination of computer keyboards), there have been no metagenomic evaluations of human hairs-a substrate commonly encountered during forensic practice. This present study attempts to address this forensic capability gap, by conducting a qualitative assessment into the applicability of metagenomic analyses of human scalp and pubic hair. Forty-two DNA extracts obtained from human scalp and pubic hairs generated a total of 79,766 reads, yielding 39,814 reads post control and abundance filtering. The results revealed the presence of unique combinations of microbial taxa that can enable discrimination between individuals and signature taxa indigenous to female pubic hairs. Microbial data from a single co-habiting couple added an extra dimension to the study by suggesting that metagenomic analyses might be of evidentiary value in sexual assault cases when other associative evidence is not present. Of all the data generated in this study, the next-generation sequencing (NGS) data generated from pubic hair held the most potential for forensic applications. Metagenomic analyses of human hairs may provide independent data to augment other forensic results and possibly provide association between victims of sexual assault and offender when other associative evidence is absent. Based on results garnered in the present study, we believe that with further development, bacterial profiling of hair will become a valuable addition to the forensic toolkit.

  4. Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study.

    Science.gov (United States)

    Kasperaviciūte, Dalia; Catarino, Claudia B; Heinzen, Erin L; Depondt, Chantal; Cavalleri, Gianpiero L; Caboclo, Luis O; Tate, Sarah K; Jamnadas-Khoda, Jenny; Chinthapalli, Krishna; Clayton, Lisa M S; Shianna, Kevin V; Radtke, Rodney A; Mikati, Mohamad A; Gallentine, William B; Husain, Aatif M; Alhusaini, Saud; Leppert, David; Middleton, Lefkos T; Gibson, Rachel A; Johnson, Michael R; Matthews, Paul M; Hosford, David; Heuser, Kjell; Amos, Leslie; Ortega, Marcos; Zumsteg, Dominik; Wieser, Heinz-Gregor; Steinhoff, Bernhard J; Krämer, Günter; Hansen, Jörg; Dorn, Thomas; Kantanen, Anne-Mari; Gjerstad, Leif; Peuralinna, Terhi; Hernandez, Dena G; Eriksson, Kai J; Kälviäinen, Reetta K; Doherty, Colin P; Wood, Nicholas W; Pandolfo, Massimo; Duncan, John S; Sander, Josemir W; Delanty, Norman; Goldstein, David B; Sisodiya, Sanjay M

    2010-07-01

    Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many other common diseases for which genetic association-studies have successfully revealed common variants associated with disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We undertook a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller effect sizes (odds ratio<1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the genetic variation emerging from whole-genome sequencing studies.

  5. Genome-wide association studies dissect the genetic networks underlying agronomical traits in soybean.

    Science.gov (United States)

    Fang, Chao; Ma, Yanming; Wu, Shiwen; Liu, Zhi; Wang, Zheng; Yang, Rui; Hu, Guanghui; Zhou, Zhengkui; Yu, Hong; Zhang, Min; Pan, Yi; Zhou, Guoan; Ren, Haixiang; Du, Weiguang; Yan, Hongrui; Wang, Yanping; Han, Dezhi; Shen, Yanting; Liu, Shulin; Liu, Tengfei; Zhang, Jixiang; Qin, Hao; Yuan, Jia; Yuan, Xiaohui; Kong, Fanjiang; Liu, Baohui; Li, Jiayang; Zhang, Zhiwu; Wang, Guodong; Zhu, Baoge; Tian, Zhixi

    2017-08-24

    Soybean (Glycine max [L.] Merr.) is one of the most important oil and protein crops. Ever-increasing soybean consumption necessitates the improvement of varieties for more efficient production. However, both correlations among different traits and genetic interactions among genes that affect a single trait pose a challenge to soybean breeding. To understand the genetic networks underlying phenotypic correlations, we collected 809 soybean accessions worldwide and phenotyped them for two years at three locations for 84 agronomic traits. Genome-wide association studies identified 245 significant genetic loci, among which 95 genetically interacted with other loci. We determined that 14 oil synthesis-related genes are responsible for fatty acid accumulation in soybean and function in line with an additive model. Network analyses demonstrated that 51 traits could be linked through the linkage disequilibrium of 115 associated loci and these links reflect phenotypic correlations. We revealed that 23 loci, including the known Dt1, E2, E1, Ln, Dt2, Fan, and Fap loci, as well as 16 undefined associated loci, have pleiotropic effects on different traits. This study provides insights into the genetic correlation among complex traits and will facilitate future soybean functional studies and breeding through molecular design.

  6. Comparative Genomic and Transcriptional Analyses of CRISPR Systems Across the Genus Pyrobaculum

    Directory of Open Access Journals (Sweden)

    David L Bernick

    2012-07-01

    Full Text Available Within the domain Archaea, the CRISPR immune system appears to be nearly ubiquitous based on computational genome analyses. Initial studies in bacteria demonstrated that the CRISPR system targets invading plasmid and viral DNA. Recent experiments in the model archaeon Pyrococcus furiosus uncovered a novel RNA-targeting variant of the CRISPR system potentially unique to archaea. Because our understanding of CRISPR system evolution in other archaea is limited, we have taken a comparative genomic and transcriptomic view of the CRISPR arrays across six diverse species within the crenarchaeal genus Pyrobaculum. We present transcriptional data from each of four species in the genus (P. aerophilum, P. islandicum, P. calidifontis, P. arsenaticum, analyzing mature CRISPR-associated small RNA abundance from over 20 arrays. Within the genus, there is remarkable conservation of CRISPR array structure, as well as unique features that are have not been studied in other archaeal systems. These unique features include: a nearly invariant CRISPR promoter, conservation of direct repeat families, the 5' polarity of CRISPR-associated small RNA abundance, and a novel CRISPR-specific association with homologues of nurA and herA. These analyses provide a genus-level evolutionary perspective on archaeal CRISPR systems, broadening our understanding beyond existing non-comparative model systems.

  7. Association between Frequency of Consumption of Fruit, Vegetables, Nuts and Pulses and BMI: Analyses of the International Study of Asthma and Allergies in Childhood (ISAAC

    Directory of Open Access Journals (Sweden)

    Clare R. Wall

    2018-03-01

    Full Text Available Diets which emphasize intakes of plant-based foods are recommended to reduce disease risk and for promoting healthy weight. The aim of this study was to examine the association between fruit, vegetables, pulses and nut intake and body mass index (BMI across countries in adolescents (13–14 years and children (6–7 years. Data from the International Study of Asthma and Allergies in Childhood; 77,243 children’s parents and 201,871 adolescents was used to examine the association between dietary intake (Food Frequency Questionnaire and BMI using general linear models, adjusting for country gross national index. Adolescents who consumed fruit, vegetables, pulses and nuts three or more times a week had a lower BMI than the never or occasional group; eating nuts three or more times a week, was associated with a BMI value of 0.274 kg/m2 lower than the never group (p < 0.001. Compared to children who never or occasionally reported eating vegetables, those reporting that they ate vegetables three or more times per week had a lower BMI of −0.079 kg/m2. In this large global study, an inverse association was observed between BMI and the reported increasing intake of vegetables in 6–7 years old and fruit, vegetables, pulses and nuts in adolescents. This study supports current dietary recommendations which emphasize the consumption of vegetables, nut and pulses, although the effect sizes were small.

  8. Macrophage Gene Expression Associated with Remodeling of the Prepartum Rat Cervix: Microarray and Pathway Analyses

    Science.gov (United States)

    Dobyns, Abigail E.; Goyal, Ravi; Carpenter, Lauren Grisham; Freeman, Tom C.; Longo, Lawrence D.; Yellon, Steven M.

    2015-01-01

    As the critical gatekeeper for birth, prepartum remodeling of the cervix is associated with increased resident macrophages (Mφ), proinflammatory processes, and extracellular matrix degradation. This study tested the hypothesis that expression of genes unique to Mφs characterizes the prepartum from unremodeled nonpregnant cervix. Perfused cervix from prepartum day 21 postbreeding (D21) or nonpregnant (NP) rats, with or without Mφs, had RNA extracted and whole genome microarray analysis performed. By subtractive analyses, expression of 194 and 120 genes related to Mφs in the cervix from D21 rats were increased and decreased, respectively. In both D21 and NP groups, 158 and 57 Mφ genes were also more or less up- or down-regulated, respectively. Mφ gene expression patterns were most strongly correlated within groups and in 5 major clustering patterns. In the cervix from D21 rats, functional categories and canonical pathways of increased expression by Mφ gene related to extracellular matrix, cell proliferation, differentiation, as well as cell signaling. Pathways were characteristic of inflammation and wound healing, e.g., CD163, CD206, and CCR2. Signatures of only inflammation pathways, e.g., CSF1R, EMR1, and MMP12 were common to both D21 and NP groups. Thus, a novel and complex balance of Mφ genes and clusters differentiated the degraded extracellular matrix and cellular genomic activities in the cervix before birth from the unremodeled state. Predicted Mφ activities, pathways, and networks raise the possibility that expression patterns of specific genes characterize and promote prepartum remodeling of the cervix for parturition at term and with preterm labor. PMID:25811906

  9. Association between Herpesviruses and Chronic Periodontitis: A Meta-Analysis Based on Case-Control Studies.

    Science.gov (United States)

    Zhu, Ce; Li, Fei; Wong, May Chun Mei; Feng, Xi-Ping; Lu, Hai-Xia; Xu, Wei

    2015-01-01

    Numerous studies have investigated the associations between herpesviruses and chronic periodontitis; however, the results remain controversial. To derive a more precise estimation, a meta-analysis on all available studies was performed to identify the association between herpesviruses and chronic periodontitis. A computerized literature search was conducted in December 2014 to identify eligible case-control studies from the PUBMED and EMBASE databases according to inclusion and exclusion criteria. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to assess the association between herpesviruses and risk of chronic periodontitis. A fixed or random effects model was determined based on a heterogeneity test. Sensitivity analysis was conducted to investigate stability and reliability. Publication bias was investigated using the Begg rank correlation test and Egger's funnel plot. Ten eligible studies were included to investigate the association between Epstein-Barr virus (EBV) and chronic periodontitis. The results showed that EBV has a significant association with chronic periodontitis compared with periodontally healthy group (OR = 5.74, 95% CI = 2.53-13.00, Pchronic periodontitis was analyzed in 10 studies. The pooled result showed that HCMV also has a significant association with chronic periodontitis (OR = 3.59, 95% CI = 1.41-9.16, P = 0.007). Similar results were found in the sensitivity analyses. No significant publication bias was observed. Two eligible studies were included to investigate the association between herpes simplex virus (HSV) and chronic periodontitis risk. The association between HSV and chronic periodontitis was inconclusive (OR = 2.81 95% CI = 0.95-8.27, P = 0.06). Only one included study investigated the association between human herpesvirus 7 (HHV-7) and chronic periodontitis risk (OR = 1.00, 95% CI = 0.21-4.86). The findings of this meta-analysis suggest that two members of the herpesvirus family, EBV

  10. Trajectory data analyses for pedestrian space-time activity study.

    Science.gov (United States)

    Qi, Feng; Du, Fei

    2013-02-25

    It is well recognized that human movement in the spatial and temporal dimensions has direct influence on disease transmission(1-3). An infectious disease typically spreads via contact between infected and susceptible individuals in their overlapped activity spaces. Therefore, daily mobility-activity information can be used as an indicator to measure exposures to risk factors of infection. However, a major difficulty and thus the reason for paucity of studies of infectious disease transmission at the micro scale arise from the lack of detailed individual mobility data. Previously in transportation and tourism research detailed space-time activity data often relied on the time-space diary technique, which requires subjects to actively record their activities in time and space. This is highly demanding for the participants and collaboration from the participants greatly affects the quality of data(4). Modern technologies such as GPS and mobile communications have made possible the automatic collection of trajectory data. The data collected, however, is not ideal for modeling human space-time activities, limited by the accuracies of existing devices. There is also no readily available tool for efficient processing of the data for human behavior study. We present here a suite of methods and an integrated ArcGIS desktop-based visual interface for the pre-processing and spatiotemporal analyses of trajectory data. We provide examples of how such processing may be used to model human space-time activities, especially with error-rich pedestrian trajectory data, that could be useful in public health studies such as infectious disease transmission modeling. The procedure presented includes pre-processing, trajectory segmentation, activity space characterization, density estimation and visualization, and a few other exploratory analysis methods. Pre-processing is the cleaning of noisy raw trajectory data. We introduce an interactive visual pre-processing interface as well as an

  11. Association between dietary nitrate and nitrite intake and site-specific cancer risk: evidence from observational studies

    Science.gov (United States)

    Jia, Hui-Xun; Liang, Fei; Yuan, Jing; Zhu, Ji

    2016-01-01

    Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30th, 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted. Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers. PMID:27486968

  12. Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study

    Directory of Open Access Journals (Sweden)

    Jonaitis Laimas

    2011-10-01

    Full Text Available Abstract Background Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS (Franke et al., 2010, for 1 association with UC in the Nordic countries, 2 for population heterogeneity between the Nordic countries and the rest of Europe, and, 3 eventually, to drive some of the previous findings towards overall genome-wide significance. Methods Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD and Cochran-Mantel-Haenszel (CMH tests were used for association analyses and heterogeneity testing. Results The rs5771069 (IL17REL SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02. No association was found between rs7809799 (SMURF1/KPNA7 and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10 or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7 in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs. Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001, rs12518307 (P = 0.007, and rs2395609 (TCP11 (P = 0

  13. Association study of interleukin-4 polymorphisms with paranoid schizophrenia in the Polish population: a critical approach.

    Science.gov (United States)

    Fila-Danilow, Anna; Kucia, Krzysztof; Kowalczyk, Malgorzata; Owczarek, Aleksander; Paul-Samojedny, Monika; Borkowska, Paulina; Suchanek, Renata; Kowalski, Jan

    2012-08-01

    Changes in immunological system are one of dysfunctions reported in schizophrenia. Some changes based on an imbalance between Th1 and Th2 cytokines results from cytokine gene polymorphisms. Interleukin-4 gene (IL4) is considered as a potential candidate gene in schizophrenia association studies. The aim of the current case-control study was to examine whether the -590C/T (rs2243250) and -33C/T (rs2070874) IL4 gene polymorphisms are implicated in paranoid schizophrenia development in the Polish population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. The genotypes and alleles distribution of both SNPs were analysed in patients (n = 182) and healthy individuals constituted the control group (n = 215). The connection between some clinical variables and studied polymorphisms has been examined as well. We did not revealed any association between the -590C/T and -33C/T polymorphisms and paranoid schizophrenia. In case of both SNPs the homozygous TT genotype was extremely rare. Both polymorphic sites of the IL4 gene were found to be in a very strong linkage disequilibrium. However we did not identify a haplotype predispose to paranoid schizophrenia. No associations were also observed between the clinical course and psychopathology of the disease and the genotypes of both analysed polymorphisms. Our results suggest that the polymorphisms -590C/T in IL4 gene promoter region and -33C/T in the 5'-UTR are not involved in the pathophysiology of paranoid schizophrenia in Polish residents.

  14. Short leukocyte telomere length is associated with obesity in American Indians: the Strong Heart Family study.

    Science.gov (United States)

    Chen, Shufeng; Yeh, Fawn; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth; Lee, Elisa T; Howard, Barbara V; Zhao, Jinying

    2014-05-01

    Shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders including cardiovascular disease (CVD) and diabetes. Obesity is an important risk factor for CVD and diabetes. The association of LTL with obesity is not well understood. This study for the first time examines the association of LTL with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study. Association of LTL with each adiposity index was examined using multivariate generalized linear mixed model, adjusting for chronological age, sex, study center, education, lifestyle (smoking, alcohol consumption, and total energy intake), high-sensitivity C-reactive protein, hypertension and diabetes. Results show that obese participants had significantly shorter LTL than non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate that LTL was significantly and inversely associated with all of the studied obesity parameters. Our results may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities.

  15. Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.

    Science.gov (United States)

    Wang, Jun; Kurilshikov, Alexander; Radjabzadeh, Djawad; Turpin, Williams; Croitoru, Kenneth; Bonder, Marc Jan; Jackson, Matthew A; Medina-Gomez, Carolina; Frost, Fabian; Homuth, Georg; Rühlemann, Malte; Hughes, David; Kim, Han-Na; Spector, Tim D; Bell, Jordana T; Steves, Claire J; Timpson, Nicolas; Franke, Andre; Wijmenga, Cisca; Meyer, Katie; Kacprowski, Tim; Franke, Lude; Paterson, Andrew D; Raes, Jeroen; Kraaij, Robert; Zhernakova, Alexandra

    2018-06-08

    In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture. Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories. We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

  16. Fluid-structure-interaction analyses of reactor vessel using improved hybrid Lagrangian Eulerian code ALICE-II

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C.Y.

    1993-06-01

    This paper describes fluid-structure-interaction and structure response analyses of a reactor vessel subjected to loadings associated with postulated accidents, using the hybrid Lagrangian-Eulerian code ALICE-II. This code has been improved recently to accommodate many features associated with innovative designs of reactor vessels. Calculational capabilities have been developed to treat water in the reactor cavity outside the vessel, internal shield structures and internal thin shells. The objective of the present analyses is to study the cover response and potential for missile generation in response to a fuel-coolant interaction in the core region. Three calculations were performed using the cover weight as a parameter. To study the effect of the cavity water, vessel response calculations for both wet- and dry-cavity designs are compared. Results indicate that for all cases studied and for the design parameters assumed, the calculated cover displacements are all smaller than the bolts` ultimate displacement and no missile generation of the closure head is predicted. Also, solutions reveal that the cavity water of the wet-cavity design plays an important role of restraining the downward displacement of the bottom head. Based on these studies, the analyses predict that the structure integrity is maintained throughout the postulated accident for the wet-cavity design.

  17. Fluid-structure-interaction analyses of reactor vessel using improved hybrid Lagrangian Eulerian code ALICE-II

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C.Y.

    1993-01-01

    This paper describes fluid-structure-interaction and structure response analyses of a reactor vessel subjected to loadings associated with postulated accidents, using the hybrid Lagrangian-Eulerian code ALICE-II. This code has been improved recently to accommodate many features associated with innovative designs of reactor vessels. Calculational capabilities have been developed to treat water in the reactor cavity outside the vessel, internal shield structures and internal thin shells. The objective of the present analyses is to study the cover response and potential for missile generation in response to a fuel-coolant interaction in the core region. Three calculations were performed using the cover weight as a parameter. To study the effect of the cavity water, vessel response calculations for both wet- and dry-cavity designs are compared. Results indicate that for all cases studied and for the design parameters assumed, the calculated cover displacements are all smaller than the bolts' ultimate displacement and no missile generation of the closure head is predicted. Also, solutions reveal that the cavity water of the wet-cavity design plays an important role of restraining the downward displacement of the bottom head. Based on these studies, the analyses predict that the structure integrity is maintained throughout the postulated accident for the wet-cavity design.

  18. No association between gender inequality and peak HIV prevalence in developing countries - an ecological study.

    Science.gov (United States)

    Kenyon, Chris R; Buyze, Jozefien

    2015-01-01

    The prevalence of both gender inequality and HIV prevalence vary considerably both within all developing countries and within those in sub-Saharan Africa. We test the hypothesis that the extent of gender inequality is associated with national peak HIV prevalence. Linear regression was used to test the association between national peak HIV prevalence and three markers of gender equality - the gender-related development index (GDI), the gender empowerment measure (GEM), and the gender inequality index (GII). No evidence was found of a positive relationship between gender inequality and HIV prevalence, either in the analyses of all developing countries or those limited to Africa. In the bivariate analyses limited to Africa, there was a positive association between the two measures of gender "equality" and peak HIV prevalence (GDI: coefficient 28, 95% confidence interval (CI) 9.1-46.8; GEM: coefficient 54.8, 95% CI 20.5-89.1). There was also a negative association between the marker of gender "inequality" and peak HIV prevalence (GII: coefficient -66.9, 95% CI -112.8 to -21.0). These associations all disappeared on multivariate analyses. We could not find any evidence to support the hypothesis that variations in the extent of gender inequality explain variations in HIV prevalence in developing countries.

  19. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

    Directory of Open Access Journals (Sweden)

    Christina M Lill

    Full Text Available More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD. To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8 association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P  =  1.3 × 10(-8. All meta-analysis results are freely available on a dedicated online database (www.pdgene.org, which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

  20. Associations between nausea, vomiting, fatigue and health-related quality of life of women in early pregnancy: The generation r study

    NARCIS (Netherlands)

    G. Bai (Guannan); I.J. Korfage (Ida); E.H.D. Hafkamp-De Groen (Esther); V.W.V. Jaddoe (Vincent); Mautner, E. (Eva); H. Raat (Hein)

    2016-01-01

    textabstractThe objective of this study was to evaluate the independent associations between nausea, vomiting, fatigue and health-related quality of life of women in early pregnancy in the Generation R study, which is a prospective mother and child cohort. Analyses were based on 5079 women in early

  1. Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

    Directory of Open Access Journals (Sweden)

    Søren D Østergaard

    2015-06-01

    Full Text Available Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR.We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49, fasting glucose (NSNPs = 36, insulin resistance (NSNPs = 10, body mass index (BMI, NSNPs = 32, total cholesterol (NSNPs = 73, HDL-cholesterol (NSNPs = 71, LDL-cholesterol (NSNPs = 57, triglycerides (NSNPs = 39, systolic blood pressure (SBP, NSNPs = 24, smoking initiation (NSNPs = 1, smoking quantity (NSNPs = 3, university completion (NSNPs = 2, and years of education (NSNPs = 1. We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3. Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8. Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3, although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28. We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1. Potential limitations of this study

  2. The impact of parent-child interaction on brain structures: cross-sectional and longitudinal analyses.

    Science.gov (United States)

    Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Asano, Kohei; Asano, Michiko; Sassa, Yuko; Yokota, Susumu; Kotozaki, Yuka; Nouchi, Rui; Kawashima, Ryuta

    2015-02-04

    There is a vast amount of evidence from psychological studies that the amount of parent-child interaction affects the development of children's verbal skills and knowledge. However, despite the vast amount of literature, brain structural development associated with the amount of parent-child interaction has never been investigated. In the present human study, we used voxel-based morphometry to measure regional gray matter density (rGMD) and examined cross-sectional correlations between the amount of time spent with parents and rGMD among 127 boys and 135 girls. We also assessed correlations between the amount of time spent with parents and longitudinal changes that occurred a few years later among 106 boys and 102 girls. After correcting for confounding factors, we found negative effects of spending time with parents on rGMD in areas in the bilateral superior temporal gyrus (STG) via cross-sectional analyses as well as in the contingent areas of the right STG. We also confirmed positive effects of spending time with parents on the Verbal Comprehension score in cross-sectional and longitudinal analyses. rGMD in partly overlapping or contingent areas of the right STG was negatively correlated with age and the Verbal Comprehension score in cross-sectional analyses. Subsequent analyses revealed verbal parent-child interactions have similar effects on Verbal Comprehension scores and rGMD in the right STG in both cross-sectional and longitudinal analyses. These findings indicate that parent-child interactions affect the right STG, which may be associated with verbal skills. Copyright © 2015 the authors 0270-6474/15/352233-13$15.00/0.

  3. Meta-analysis for genome-wide association studies using case-control design: application and practice.

    Science.gov (United States)

    Shim, Sungryul; Kim, Jiyoung; Jung, Wonguen; Shin, In-Soo; Bae, Jong-Myon

    2016-01-01

    This review aimed to arrange the process of a systematic review of genome-wide association studies in order to practice and apply a genome-wide meta-analysis (GWMA). The process has a series of five steps: searching and selection, extraction of related information, evaluation of validity, meta-analysis by type of genetic model, and evaluation of heterogeneity. In contrast to intervention meta-analyses, GWMA has to evaluate the Hardy-Weinberg equilibrium (HWE) in the third step and conduct meta-analyses by five potential genetic models, including dominant, recessive, homozygote contrast, heterozygote contrast, and allelic contrast in the fourth step. The 'genhwcci' and 'metan' commands of STATA software evaluate the HWE and calculate a summary effect size, respectively. A meta-regression using the 'metareg' command of STATA should be conducted to evaluate related factors of heterogeneities.

  4. Meta-analyses of the Association of Sleep Apnea with Insulin Resistance, and the Effects of CPAP on HOMA-IR, Adiponectin, and Visceral Adipose Fat.

    Science.gov (United States)

    Iftikhar, Imran H; Hoyos, Camilla M; Phillips, Craig L; Magalang, Ulysses J

    2015-04-15

    We sought to conduct an updated meta-analysis of randomized controlled trials (RCTs) on the effect of continuous positive airway pressure (CPAP) on insulin resistance, as measured by homeostasis model assessment of insulin resistance (HOMA-IR), visceral abdominal fat (VAF), and adiponectin. Additionally, we performed a separate meta-analysis and meta-regression of studies on the association of insulin resistance and obstructive sleep apnea (OSA). All included studies were searched from PubMed (from conception to March 15, 2014). Data were pooled across all included RCTs as the mean difference in HOMA-IR and VAF, and as the standardized mean difference in the case of adiponectin analysis. From the included case-control studies, data on the difference of HOMA-IR between cases and controls were pooled across all studies, as the standardized mean difference (SMD). There was a significant difference in HOMA-IR (-0.43 [95% CIs: -0.75 to -0.11], p = 0.008) between CPAP treated and non CPAP treated participants. However, there was no significant difference in VAF or adiponectin; (-47.93 [95% CI: -112.58 to 16.72], p = 0.14) and (-0.06 [95% CI: -0.28 to 0.15], p = 0.56), respectively. Meta-analysis of 16 case-control studies showed a pooled SMD in HOMA-IR of 0.51 (95% CI: 0.28 to 0.75), p ≤ 0.001, between cases and controls. The results of our meta-analyses show that CPAP has a favorable effect on insulin resistance. This effect is not associated with any significant changes in total adiponectin levels or amount of VAF. Our findings also confirm a significant association between OSA and insulin resistance. © 2015 American Academy of Sleep Medicine.

  5. Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

    Science.gov (United States)

    Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

    2014-07-16

    To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

  6. Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale Study

    DEFF Research Database (Denmark)

    Prompers, L.; Huijberts, M.; Schaper, N.

    2008-01-01

    Aims/hypothesis The aim of the present study was to investigate resource utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in resource utilisation between individuals with or without peripheral arterial disease (PAD) and/or infection. Methods Data....... In view of the magnitude of the costs associated with in-hospital stay, reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease Udgivelsesdato: 2008/10...

  7. Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.

    Directory of Open Access Journals (Sweden)

    Thijs C van Holten

    Full Text Available BACKGROUND: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. METHODS AND FINDINGS: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. CONCLUSIONS: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a

  8. Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: a cross-sectional, descriptive analysis

    Directory of Open Access Journals (Sweden)

    Davey Jonathan

    2011-11-01

    Full Text Available Abstract Background Cochrane systematic reviews collate and summarise studies of the effects of healthcare interventions. The characteristics of these reviews and the meta-analyses and individual studies they contain provide insights into the nature of healthcare research and important context for the development of relevant statistical and other methods. Methods We classified every meta-analysis with at least two studies in every review in the January 2008 issue of the Cochrane Database of Systematic Reviews (CDSR according to the medical specialty, the types of interventions being compared and the type of outcome. We provide descriptive statistics for numbers of meta-analyses, numbers of component studies and sample sizes of component studies, broken down by these categories. Results We included 2321 reviews containing 22,453 meta-analyses, which themselves consist of data from 112,600 individual studies (which may appear in more than one meta-analysis. Meta-analyses in the areas of gynaecology, pregnancy and childbirth (21%, mental health (13% and respiratory diseases (13% are well represented in the CDSR. Most meta-analyses address drugs, either with a control or placebo group (37% or in a comparison with another drug (25%. The median number of meta-analyses per review is six (inter-quartile range 3 to 12. The median number of studies included in the meta-analyses with at least two studies is three (inter-quartile range 2 to 6. Sample sizes of individual studies range from 2 to 1,242,071, with a median of 91 participants. Discussion It is clear that the numbers of studies eligible for meta-analyses are typically very small for all medical areas, outcomes and interventions covered by Cochrane reviews. This highlights the particular importance of suitable methods for the meta-analysis of small data sets. There was little variation in number of studies per meta-analysis across medical areas, across outcome data types or across types of

  9. Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies

    DEFF Research Database (Denmark)

    Ellinghaus, David; Zhang, Hu; Zeissig, Sebastian

    2013-01-01

    BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through...... detailed sequencing, genetic association, expression, and functional studies. METHODS: We sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico...... mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems. RESULTS: We identified rare...

  10. EVALUATION OF ANAEMIA USING RED CELL AND RETICULOCYTE PARAMETERS USING AUTOMATED HAEMATOLOGY ANALYSER

    Directory of Open Access Journals (Sweden)

    Vidyadhar Rao

    2016-06-01

    Full Text Available Use of current models of Automated Haematology Analysers help in calculating the haemoglobin contents of the mature Red cells, Reticulocytes and percentages of Microcytic and hypochromic Red cells. This has helped the clinician in reaching early diagnosis and management of Different haemopoietic disorders like Iron Deficiency Anaemia, Thalassaemia and anaemia of chronic diseases. AIM This study is conducted using an Automated Haematology Analyser to evaluate anaemia using the Red Cell and Reticulocyte parameters. Three types of anaemia were evaluated; iron deficiency anaemia, anaemia of long duration and anaemia associated with chronic disease and Iron deficiency. MATERIALS AND METHODS The blood samples were collected from 287 adult patients with anaemia differentiated depending upon their iron status, haemoglobinopathies and inflammatory activity. Iron deficiency anaemia (n=132, anaemia of long duration (ACD, (n=97 and anaemia associated with chronic disease with iron deficiency (ACD Combi, (n=58. Microcytic Red cells, hypochromic red cells percentage and levels of haemoglobin in reticulocytes and matured RBCs were calculated. The accuracy of the parameters was analysed using receiver operating characteristic analyser to differentiate between the types of anaemia. OBSERVATIONS AND RESULTS There was no difference in parameters between the iron deficiency group or anaemia associated with chronic disease and iron deficiency. The hypochromic red cells percentage was the best parameter in differentiating anaemia of chronic disease with or without absolute iron deficiency with a sensitivity of 72.7% and a specificity of 70.4%. CONCLUSIONS The parameters of red cells and reticulocytes were of reasonably good indicators in differentiating the absolute iron deficiency anaemia with chronic disease.

  11. Association between Cognition and Serum Insulin-Like Growth Factor-1 in Middle-Aged & Older Men: An 8 Year Follow-Up Study.

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    Shankar Tumati

    Full Text Available Low levels of insulin-like growth factor-1 (IGF-1, an essential neurotrophic factor, have been associated with worse cognitive function in older adults. However, few studies have assessed the prospective association of serum IGF-1 with cognitive function. We aimed to determine the association between serum IGF-1 on concurrent and prospective cognitive function in a population sample of men aged 40-80 years. Blood samples were assessed for IGF-1 levels at baseline and neuropsychological assessments were performed at baseline (n = 400 and at follow-up after a mean duration of 8.3 years (n = 286. Linear regression analyses were carried out to determine the associations between quintiles of IGF-1 and cognitive function at the baseline and follow-up visits. Results showed that those in the top quintile of IGF-1 had lower processing capacity and global cognition scores at follow-up after controlling for cognitive function at baseline and other confounding factors. Additional analyses exploring associations with IGF-1 separately in middle-aged and older participants, and with quartiles of IGF-1 produced similar results. In those older than 60 years, high IGF-1 levels were also associated with lower baseline processing capacity. These results suggest that high IGF-1 levels are associated with worse long-term cognition in men. Together with past studies, we suggest that both, high and low levels of IGF-1 may be associated with poor cognitive function and that optimum levels of IGF-1 (quintile 2 and 3 in current study may be associated with better cognitive function.

  12. Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

    DEFF Research Database (Denmark)

    Imamura, Minako; Takahashi, Atsushi; Yamauchi, Toshimasa

    2016-01-01

    Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery...... and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P2, rs7107784 near MIR4686 and rs67839313 near INAFM2....... Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P

  13. Psychological workload is associated with weight gain between 1993 and 1999: analyses based on the Danish Nurse Cohort Study

    DEFF Research Database (Denmark)

    Overgaard, D.; Gamborg, M.; Gyntelberg, Finn

    2004-01-01

    AIMS: To examine associations between psychological workload and subsequent 6-y weight changes. METHODS: In total, 6704 Danish nurses, aged 45-65 y and employed both in 1993 and 1999, answered questionnaires about psychological workload, including busyness in job, job speed and job influence...... who attained influence in job over the 6-y period. CONCLUSION: : Psychological workload, particularly both low and high busyness in job and low influence in job, was associated with higher 6-y weight gain among female Danish nurses....

  14. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

    Science.gov (United States)

    Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A

    2016-11-01

    Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

  15. Site-Specific Analyses for Demonstrating Compliance with 10 CFR 61 Performance Objectives - 12179

    Energy Technology Data Exchange (ETDEWEB)

    Grossman, C.J.; Esh, D.W.; Yadav, P.; Carrera, A.G. [U.S. Nuclear Regulatory Commission, 11545 Rockville Pike, Rockville, MD 20852 (United States)

    2012-07-01

    The U.S. Nuclear Regulatory Commission (NRC) is proposing to amend its regulations at 10 CFR Part 61 to require low-level radioactive waste disposal facilities to conduct site-specific analyses to demonstrate compliance with the performance objectives in Subpart C. The amendments would require licensees to conduct site-specific analyses for protection of the public and inadvertent intruders as well as analyses for long-lived waste. The amendments would ensure protection of public health and safety, while providing flexibility to demonstrate compliance with the performance objectives, for current and potential future waste streams. NRC staff intends to submit proposed rule language and associated regulatory basis to the Commission for its approval in early 2012. The NRC staff also intends to develop associated guidance to accompany any proposed amendments. The guidance is intended to supplement existing low-level radioactive waste guidance on issues pertinent to conducting site-specific analyses to demonstrate compliance with the performance objectives. The guidance will facilitate implementation of the proposed amendments by licensees and assist competent regulatory authorities in reviewing the site-specific analyses. Specifically, the guidance provides staff recommendations on general considerations for the site-specific analyses, modeling issues for assessments to demonstrate compliance with the performance objectives including the performance assessment, intruder assessment, stability assessment, and analyses for long-lived waste. This paper describes the technical basis for changes to the rule language and the proposed guidance associated with implementation of the rule language. The NRC staff, per Commission direction, intends to propose amendments to 10 CFR Part 61 to require licensees to conduct site-specific analyses to demonstrate compliance with performance objectives for the protection of public health and the environment. The amendments would require a

  16. Genome-wide association study identifies candidate genes for male fertility traits in humans.

    Science.gov (United States)

    Kosova, Gülüm; Scott, Nicole M; Niederberger, Craig; Prins, Gail S; Ober, Carole

    2012-06-08

    Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. Pregnancy-associated transient osteoporosis of the hip: results of a case-control study.

    Science.gov (United States)

    Hadji, Peyman; Boekhoff, Jelena; Hahn, Melitta; Hellmeyer, Lars; Hars, Olaf; Kyvernitakis, Ioannis

    2017-12-01

    The etiology and underlying mechanisms of transient of osteoporosis of the hip (TOH) during pregnancy are still unclear, since no systematic analyses exist. Our results support the hypothesis that TOH is a multifactorial disease, which is associated with immobility, dental problems, and lack of exercise in childhood. Pregnancy-associated transient osteoporosis of the hip (TOH) is a rare but severe form of osteoporosis, which may affect a subgroup of women in the last trimester of pregnancy or immediately postpartum. Common symptoms include acute pain of the hip(s) due to bone marrow edema or even hip fractures. The exact underlining mechanisms of this disorder are still unknown since no published systematic analyses exist. Out of a total of 52 TOH patients, 33 TOH patients could be matched with 33 healthy controls according to age, region, and gravity. The aim of this retrospective case-control study was to evaluate the risk factors for TOH in a homogenous population of women. The baseline characteristics of the two study groups were similar. Overall, 12.1% of the TOH patients sustained a hip fracture. Expectedly, 90.9% of the TOH patients complained about pain of the hip (p ≤ 0.001). TOH patients suffered more frequently from severe dental problems during childhood (p = 0.023) and performed less often sports before and after puberty (p ≤ 0.001), whereas the frequency of immobilization during pregnancy was threefold higher compared to the control group (p = 0.007). We found a significant increase of the TOH risk in patients with dental problems in childhood (OR 3.7; CI 1.3-10.7) as well as in patients with lack of exercise during childhood (OR 4.2; CI 1.3-12.9). Our results support the hypothesis that pregnancy-associated TOH is a multifactorial disease, to which several individual factors may contribute. Hereby, we found significant associations with immobility, dental problems, and lack of exercise in childhood.

  18. The Association between Bone Quality and Atherosclerosis: Results from Two Large Population-Based Studies

    Directory of Open Access Journals (Sweden)

    V. Lange

    2017-01-01

    Full Text Available Objective. It is highly debated whether associations between osteoporosis and atherosclerosis are independent of cardiovascular risk factors. We aimed to explore the associations between quantitative ultrasound (QUS parameters at the heel with the carotid artery intima-media thickness (IMT, the presence of carotid artery plaques, and the ankle-brachial index (ABI. Methods. The study population comprised 5680 men and women aged 20–93 years from two population-based cohort studies: Study of Health in Pomerania (SHIP and SHIP-Trend. QUS measurements were performed at the heel. The extracranial carotid arteries were examined with B-mode ultrasonography. ABI was measured in a subgroup of 3853 participants. Analyses of variance and linear and logistic regression models were calculated and adjusted for major cardiovascular risk factors. Results. Men but not women had significantly increased odds for carotid artery plaques with decreasing QUS parameters independent of diabetes mellitus, dyslipidemia, and hypertension. Beyond this, the QUS parameters were not significantly associated with IMT or ABI in fully adjusted models. Conclusions. Our data argue against an independent role of bone metabolism in atherosclerotic changes in women. Yet, in men, associations with advanced atherosclerosis, exist. Thus, men presenting with clinical signs of osteoporosis may be at increased risk for atherosclerotic disease.

  19. The Association between Bone Quality and Atherosclerosis: Results from Two Large Population-Based Studies.

    Science.gov (United States)

    Lange, V; Dörr, M; Schminke, U; Völzke, H; Nauck, M; Wallaschofski, H; Hannemann, A

    2017-01-01

    It is highly debated whether associations between osteoporosis and atherosclerosis are independent of cardiovascular risk factors. We aimed to explore the associations between quantitative ultrasound (QUS) parameters at the heel with the carotid artery intima-media thickness (IMT), the presence of carotid artery plaques, and the ankle-brachial index (ABI). The study population comprised 5680 men and women aged 20-93 years from two population-based cohort studies: Study of Health in Pomerania (SHIP) and SHIP-Trend. QUS measurements were performed at the heel. The extracranial carotid arteries were examined with B-mode ultrasonography. ABI was measured in a subgroup of 3853 participants. Analyses of variance and linear and logistic regression models were calculated and adjusted for major cardiovascular risk factors. Men but not women had significantly increased odds for carotid artery plaques with decreasing QUS parameters independent of diabetes mellitus, dyslipidemia, and hypertension. Beyond this, the QUS parameters were not significantly associated with IMT or ABI in fully adjusted models. Our data argue against an independent role of bone metabolism in atherosclerotic changes in women. Yet, in men, associations with advanced atherosclerosis, exist. Thus, men presenting with clinical signs of osteoporosis may be at increased risk for atherosclerotic disease.

  20. The short-term effects of air pollutants on respiratory disease mortality in Wuhan, China: comparison of time-series and case-crossover analyses.

    Science.gov (United States)

    Ren, Meng; Li, Na; Wang, Zhan; Liu, Yisi; Chen, Xi; Chu, Yuanyuan; Li, Xiangyu; Zhu, Zhongmin; Tian, Liqiao; Xiang, Hao

    2017-01-13

    Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified-case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 μg/m 3 increment in SO 2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO 2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case-crossover analysis displayed greater variation than that from the time-series analysis.

  1. Effect of periodontal treatment on preterm birth rate: a systematic review of meta-analyses.

    Science.gov (United States)

    López, Néstor J; Uribe, Sergio; Martinez, Benjamín

    2015-02-01

    Preterm birth is a major cause of neonatal morbidity and mortality in both developed and developing countries. Preterm birth is a highly complex syndrome that includes distinct clinical subtypes in which many different causes may be involved. The results of epidemiological, molecular, microbiological and animal-model studies support a positive association between maternal periodontal disease and preterm birth. However, the results of intervention studies carried out to determine the effect of periodontal treatment on reducing the risk of preterm birth are controversial. This systematic review critically analyzes the methodological issues of meta-analyses of the studies to determine the effect of periodontal treatment to reduce preterm birth. The quality of the individual randomized clinical trials selected is of highest relevance for a systematic review. This article describes the methodological features that should be identified a priori and assessed individually to determine the quality of a randomized controlled trial performed to evaluate the effect of periodontal treatment on pregnancy outcomes. The AMSTAR and the PRISMA checklist tools were used to assess the quality of the six meta-analyses selected, and the bias domain of the Cochrane Collaboration's Tool was applied to evaluate each of the trials included in the meta-analyses. In addition, the methodological characteristics of each clinical trial were assessed. The majority of the trials included in the meta-analyses have significant methodological flaws that threaten their internal validity. The lack of effect of periodontal treatment on preterm birth rate concluded by four meta-analyses, and the positive effect of treatment for reducing preterm birth risk concluded by the remaining two meta-analyses are not based on consistent scientific evidence. Well-conducted randomized controlled trials using rigorous methodology, including appropriate definition of the exposure, adequate control of confounders for

  2. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

    Science.gov (United States)

    Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; van der Veen, JP Wietze; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A; Spritz, Richard A

    2016-01-01

    Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment. PMID:27723757

  3. Methodological barriers to studying the association between the economic crisis and suicide in Spain

    Directory of Open Access Journals (Sweden)

    Javier Alvarez-Galvez

    2017-09-01

    Full Text Available Abstract Background The hypothetical relationship between economic recession and the increase in suicides in Spain is subject to various arguments. In addition to the inherent complexity of capturing and explaining the underlining mechanisms that could describe this causal link, different points of contention have been be identified. The period of this association and its possible starting points, the socioeconomic determinants that may explain the variation in suicide rate, and the data sources available are the main focus of controversy. The present study aims to identify the phases of association between different periods of economic recession and suicide rates, and compare the effect of different social determinants of health that have been mentioned in previous studies. Methods We have used interrupted time series analyses to assess the impact of economic recession on national rates of suicide mortality provided by the Spanish Statistical Office (1980–2014. In an attempt to consider the factors that have affected the study of suicide in Spain, different data sources/periods, predictors, and regions in Spain were analysed. Results The analysis revealed a positive and significant relationship between the Great Recession and suicide rates during the second period of economic recession (2011–2014, while appeared to decrease during the first recession period. However, the first decreasing trend was not statistically significant in the global analysis of the evolution of monthly suicide rates for the entire country. Both unemployment and per capita GDP were positively related to suicide trends. Finally, the regional analysis demonstrates a similar pattern in different Spanish areas. Conclusion Although previous studies have mentioned the double-dip in the suicide rate associated with the corresponding period of double recession, our study only identify a positive relationship during the second recession period. These results points out that

  4. Fruit and vegetable intake is associated with frequency of breakfast, lunch and evening meal: cross-sectional study of 11-, 13-, and 15-year-olds

    Directory of Open Access Journals (Sweden)

    Pedersen Trine

    2012-02-01

    Full Text Available Abstract Background Frequency of eating breakfast, lunch and evening meal as a determinant of fruit and vegetable intake among young people is little studied. We investigated whether irregular meal consumption was associated with fruit and vegetable intake among adolescents. We used separate analyses, and special emphasis was on the potentially modifying effect of sex and age. Methods Data were from the Danish contribution to the international collaborative Health Behavior in School-Aged Children Study (HBSC in 2002. We used a questionnaire-based, cross-sectional design to study schoolchildren aged 11, 13 and 15 years (n = 3913 selected from a random sample of schools in Denmark. Fruit intake and vegetable intake were measured by a food frequency questionnaire and analyses were conducted using multivariate logistic regression. Results Overall, statistically significant associations were found between irregular breakfast, lunch and evening meal consumption and low frequency of fruit intake and vegetable intake (breakfast: fruit OR = 1.42, vegetables OR = 1.48; lunch: fruit OR = 1.68, vegetables OR = 1.83; evening meal: vegetables OR = 1.70. No association was found for irregular evening meal consumption and low frequency of fruit intake. Analyses stratified by sex showed that the associations between irregular breakfast consumption and both fruit and vegetable intake remained statistically significant only among girls. When analyses were stratified by both sex and age, different patterns appeared. Overall, skipping meals seemed to be a less serious risk factor for low frequency of fruit and vegetable intake among younger participants compared with those who were older. This was especially evident for skipping breakfast. The same tendency was also seen for skipping lunch and evening meal, although the age pattern varied between boys and girls and between fruit and vegetable intake. Conclusion Our results showed that irregular breakfast, lunch and

  5. Investigation of publication bias in meta-analyses of diagnostic test accuracy: a meta-epidemiological study

    NARCIS (Netherlands)

    van Enst, W. Annefloor; Ochodo, Eleanor; Scholten, Rob J. P. M.; Hooft, Lotty; Leeflang, Mariska M.

    2014-01-01

    The validity of a meta-analysis can be understood better in light of the possible impact of publication bias. The majority of the methods to investigate publication bias in terms of small study-effects are developed for meta-analyses of intervention studies, leaving authors of diagnostic test

  6. Association of atopic diseases and attention-deficit/hyperactivity disorder : A systematic review and meta-analyses

    NARCIS (Netherlands)

    van der Schans, Jurjen; Cicek, Rukiye; de Vries, Tjalling W.; Hak, Eelko; Hoekstra, Pieter J.

    Over the last decades, the hypothesis has been raised that an atopic response could lead to the development of attention-deficit/hyperactivity disorder (ADHD). This study systematically reviews the observational cross-sectional and longitudinal studies that assessed the association between atopic

  7. Meta-analysis of the association between COX-2 polymorphisms and risk of colorectal cancer based on case-control studies.

    Directory of Open Access Journals (Sweden)

    Qiliu Peng

    Full Text Available OBJECTIVE: Cyclooxygenase-2 (COX-2 is an inducible enzyme converting arachidonic acid to prostaglandins and playing important roles in inflammatory diseases as well as tumor development. Previous studies investigating the association between COX-2 polymorphisms and colorectal cancer (CRC risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. METHODS: All studies published up to October 2013 on the association between COX-2 polymorphisms and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between COX-2 polymorphisms and CRC risk was assessed by odds ratios (ORs together with their 95% confidence intervals (CIs. RESULTS: Ten studies with 6,774 cases and 9,772 controls were included for -1195A>G polymorphism, 13 studies including 6,807 cases and 10,052 controls were available for -765G>C polymorphism, and 8 studies containing 5,121 cases and 7,487 controls were included for 8473T>C polymorphism. With respect to -765G>C polymorphism, we did not find a significant association with CRC risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and cancer location, with a Bonferroni corrected alpha of 0.05/2, statistical significant increased CRC risk was found in the Asian populations (dominant model CC+CG vs. GG: OR = 1.399, 95%CI: 1.113-1.760, P = 0.004 and rectum cancer patients (CC vs. GG: OR = 2.270, 95%CI: 1.295-3.980, P = 0.004; Recessive model CC vs. CG+GG: OR = 2.269, 95%CI: 1.297-3.970, P = 0.004. In subgroup analysis according to source of control, no significant association was detected. With respect to -1195A>G and 8473T>C polymorphisms, no significant association with CRC risk was demonstrated in the overall and subgroup analyses. CONCLUSIONS: The present meta-analysis suggests that the COX-2 -765G>C polymorphism may be a risk factor for

  8. The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects

    NARCIS (Netherlands)

    Rangel, I.; Sundin, J.; Fuentes Enriquez de Salamanca, S.; Repsilber, D.; Vos, de W.M.; Brummer, R.J.

    2015-01-01

    BACKGROUND: The faecal-associated microbiota is commonly seen as a surrogate of the mucosal-associated microbiota. However, previous studies indicate that they are different. Furthermore, analyses of the mucosal microbiota are commonly done after standard bowel cleansing, affecting the microbial

  9. Meta-analysis for genome-wide association studies using case-control design: application and practice

    Directory of Open Access Journals (Sweden)

    Sungryul Shim

    2016-12-01

    Full Text Available This review aimed to arrange the process of a systematic review of genome-wide association studies in order to practice and apply a genome-wide meta-analysis (GWMA. The process has a series of five steps: searching and selection, extraction of related information, evaluation of validity, meta-analysis by type of genetic model, and evaluation of heterogeneity. In contrast to intervention meta-analyses, GWMA has to evaluate the Hardy–Weinberg equilibrium (HWE in the third step and conduct meta-analyses by five potential genetic models, including dominant, recessive, homozygote contrast, heterozygote contrast, and allelic contrast in the fourth step. The ‘genhwcci’ and ‘metan’ commands of STATA software evaluate the HWE and calculate a summary effect size, respectively. A meta-regression using the ‘metareg’ command of STATA should be conducted to evaluate related factors of heterogeneities.

  10. Comparison of plasma input and reference tissue models for analysing [(11)C]flumazenil studies

    NARCIS (Netherlands)

    Klumpers, Ursula M. H.; Veltman, Dick J.; Boellaard, Ronald; Comans, Emile F.; Zuketto, Cassandra; Yaqub, Maqsood; Mourik, Jurgen E. M.; Lubberink, Mark; Hoogendijk, Witte J. G.; Lammertsma, Adriaan A.

    2008-01-01

    A single-tissue compartment model with plasma input is the established method for analysing [(11)C]flumazenil ([(11)C]FMZ) studies. However, arterial cannulation and measurement of metabolites are time-consuming. Therefore, a reference tissue approach is appealing, but this approach has not been

  11. Tomographic local 2D analyses of the WISExSuperCOSMOS all-sky galaxy catalogue

    Science.gov (United States)

    Novaes, C. P.; Bernui, A.; Xavier, H. S.; Marques, G. A.

    2018-05-01

    The recent progress in obtaining larger and deeper galaxy catalogues is of fundamental importance for cosmological studies, especially to robustly measure the large scale density fluctuations in the Universe. The present work uses the Minkowski Functionals (MF) to probe the galaxy density field from the WISExSuperCOSMOS (WSC) all-sky catalogue by performing tomographic local analyses in five redshift shells (of thickness δz = 0.05) in the total range of 0.10 methodology reveals 1 - 3 regions of the GNC maps in each redshift shell with an uncommon behaviour (extreme regions), i.e., p-value < 1.4%. Indeed, the resulting MF curves show signatures that suggest the uncommon behaviour to be associated with the presence of over- or under-densities there, but contamination due to residual foregrounds is not discarded. Additionally, even though our analyses indicate a good agreement among data and simulations, we identify 1 highly extreme region, seemingly associated to a large clustered distribution of galaxies. Our results confirm the usefulness of the MF to analyse GNC maps from photometric galaxy datasets.

  12. Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins

    DEFF Research Database (Denmark)

    Starnawska, Anna; Tan, Qihua; McGue, Matt

    2017-01-01

    As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenance......, and synaptic plasticity. Using the twin design we performed an epigenome-wide association study (EWAS) in a population of 486 middle-aged monozygotic twins (mean age at follow-up 65.9, SD = 6.1) and correlated their blood DNA methylation to their level (cross-sectional analysis) and change in cognitive...... abilities over 10 years (longitudinal analysis). We identified several CpG sites where cross-sectional cognitive functioning was associated with DNA methylation levels. The top identified loci were located in ZBTB46 (p = 5.84 × 10-7), and TAF12 (p = 4.91 × 10-7). KEGG's enrichment analyses of the most...

  13. The effect of English-language restriction on systematic review-based meta-analyses: a systematic review of empirical studies.

    Science.gov (United States)

    Morrison, Andra; Polisena, Julie; Husereau, Don; Moulton, Kristen; Clark, Michelle; Fiander, Michelle; Mierzwinski-Urban, Monika; Clifford, Tammy; Hutton, Brian; Rabb, Danielle

    2012-04-01

    The English language is generally perceived to be the universal language of science. However, the exclusive reliance on English-language studies may not represent all of the evidence. Excluding languages other than English (LOE) may introduce a language bias and lead to erroneous conclusions. We conducted a comprehensive literature search using bibliographic databases and grey literature sources. Studies were eligible for inclusion if they measured the effect of excluding randomized controlled trials (RCTs) reported in LOE from systematic review-based meta-analyses (SR/MA) for one or more outcomes. None of the included studies found major differences between summary treatment effects in English-language restricted meta-analyses and LOE-inclusive meta-analyses. Findings differed about the methodological and reporting quality of trials reported in LOE. The precision of pooled estimates improved with the inclusion of LOE trials. Overall, we found no evidence of a systematic bias from the use of language restrictions in systematic review-based meta-analyses in conventional medicine. Further research is needed to determine the impact of language restriction on systematic reviews in particular fields of medicine.

  14. The Associations between Perceived Parenting Styles, Empathy, and Altruistic Choices in Economic Games: A Study of Chinese Children.

    Science.gov (United States)

    Guo, Qingke; Feng, Linlin

    2017-01-01

    Parenting styles are critical for fostering children's empathy and prosociality. Yet these relations haven't been well established for Chinese children, and the underlying mechanisms were seldom explored. Drawing upon parental acceptance-rejection theory and empathy-altruism hypothesis, the objective of this study was to investigate the relationships between perceived parenting styles and altruistic behavior of children, and the intervening role of children's empathy and the moderating role of in-group and out-group conditions. What is novel about this study is that it contains both survey data and experimental data. Four hundred and ninety-four children ( M age = 8.92 years) completed four simple binary-choice dictator games which are widely used in the study of other-regarding preferences (concerns for the interests of others). These children also reported their perceived parenting styles. And children's empathy was reported by their mothers. Each child's altruism score, which was used in the subsequent analyses, was derived from the altruistic choices in these games. Mediation analyses indicated that, when age and gender were controlled for, maternal and paternal emotional warmth were positively associated with children's altruism via children's empathy, while maternal and paternal rejection were negatively associated with children's altruism via children's empathy. Multi-group analyses showed that the influences of perceived parenting styles on children's altruistic behavior via children's empathy were consistent for in-group and out-group conditions. These findings suggest that enhancing parental emotional warmth and reducing parental rejection may foster children's empathy, which in turn promote children's altruism. Limitations and future directions of this study were also discussed.

  15. The association between exposure to psychosocial work factors and mental health in older employees, a 3-year follow-up study.

    Science.gov (United States)

    Havermans, Bo M; Boot, Cécile R L; Hoekstra, Trynke; Houtman, Irene L D; Brouwers, Evelien P M; Anema, Johannes R; van der Beek, Allard J

    2018-01-01

    Unfavourable exposure to psychosocial work factors threatens older employees' mental health, and their sustained employment. This study assesses whether an improved compared to stable unfavourable and stable favourable exposure to psychosocial work factors is associated with a change in mental health in older employees at 3-year follow-up. The current study used data from the Study on Transitions in Employment, Ability and Motivation (STREAM), in workers aged 45-65 years (n = 5249). Two-year (2010-2012) exposure was assessed for psychological demands, autonomy, support, mental load, and distributive justice. Linear regression analyses were performed to compare improved exposure to unfavourable psychosocial work factors with stable unfavourable and stable favourable exposure and mental health at follow-up (2013), corrected for confounders. Analyses were stratified for age groups (45-54 and 55-65 years) and gender. In certain subgroups, stable unfavourable exposure to psychological demands, autonomy, support, and distributive justice was associated with a significantly lower mental health score than improved exposure. Stable favourable exposure to support was associated with a higher mental health score than improved support, whereas stable favourable exposure to autonomy was associated with a lower mental health score compared to improved exposure. There is a longitudinal association between changes in exposure to psychosocial work factors and mental health. Improvement in unfavourable exposure to psychosocial work factors was associated with improved mental health. This is important information for organisations that consider deploying measures to improve the psychosocial work environment of older workers.

  16. Prevalence of Helicobacter pylori infection and associated factors among adults in Southern Brazil: a population-based cross-sectional study

    Directory of Open Access Journals (Sweden)

    Halal Camila S

    2005-11-01

    Full Text Available Abstract Background Helicobacter pylori (Hp infection is associated with several upper gastrointestinal disorders. Local data on the epidemiology of the infection are scarce in Brazil. The purpose of this study is to measure the prevalence rate and to explore the associated factors among the adult population living in Pelotas, a southern Brazilin city. Methods This was a population-based cross-sectional study. Through a multi-stage sampling method all individuals 20 years and over living at the selected households at the urban area of the city were interviewed regarding past and current socio-economic indicators; demographic characteristics; nutritional and behavioural habits; and history of upper gastrointestinal symptoms.Hp infection was ascertained through the 13C-UBT. Due to the high prevalence, data were analysed through robust Poisson regression. All analyses took into account the family clustering of the data. Results Among 563 eligible individuals, 363 agreed to perform the 13C-UBT (refusal rate of 35.5%. Refusals were associated with female sex, consumption of mate drinking, and presence of upper gastrointestinal symptoms. The prevalence rate of H. pylori infection was 63.4% (95%CI 59.3%–69.3%. In crude analyses, prevalence was associated with increasing age, non-white skin colour, lower current family income, lower education level, higher size of the family, low socio-economic conditions in childhood, higher number of siblings and attendance to day-care centres in childhood, and presence of dyspeptic symptoms. In adjusted analysis the level of education of the father was inversely associated with the infection, whereas number of siblings and attendance to day-care centre in childhood were directly associated with it. Non-white skin colour remained significantly associated with increased prevalence even after allowing for past and current socio-economic characteristics, age and sex. Compared to non-symptomatic individuals, those

  17. Prediabetes and Type 2 Diabetes Are Associated With Generalized Microvascular Dysfunction: The Maastricht Study.

    Science.gov (United States)

    Sörensen, Ben M; Houben, Alfons J H M; Berendschot, Tos T J M; Schouten, Jan S A G; Kroon, Abraham A; van der Kallen, Carla J H; Henry, Ronald M A; Koster, Annemarie; Sep, Simone J S; Dagnelie, Pieter C; Schaper, Nicolaas C; Schram, Miranda T; Stehouwer, Coen D A

    2016-11-01

    Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia. In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean±standard deviation] 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease. Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46

  18. Physical inactivity mediates the association between the perceived exercising behavior of social network members and obesity: a cross-sectional study.

    Science.gov (United States)

    Leroux, Janette S; Moore, Spencer; Richard, Lucie; Gauvin, Lise

    2012-01-01

    Social networks influence the spread of depression, health behaviors, and obesity. The social networks of older urban-dwelling adults were examined to assess whether physical inactivity mediated the association between social networks and obesity. Data come from the Montreal Neighborhood Networks and Healthy Aging study (n=2707). Self-reported height and weight were used to calculate body mass index (BMI) with obesity defined as a BMI ≥ 30. A name generator/interpreter instrument was used to elicit participants' core ties (i.e., alters), and assess whether alters exercised regularly and resided in participants' neighborhoods. The International Physical Activity Questionnaire was used to measure physical inactivity. Separate multilevel logistic regression analyses were conducted for younger (18-54 years) and older (55 years plus) age groups to examine the association between the exercising behavior of alters and obesity. Ancillary analyses examined whether the residential location of alters was associated with obesity. Mediation analyses assessed whether physical inactivity mediated the association between alter exercising behavior and obesity. Models adjusted for participant socio-demographic and -economic characteristics. Among the older age stratum (55 years plus), physically inactive individuals were more likely obese (OR 2.14; 95% CIs: 1.48-3.10); participants who had more exercising alters were less likely obese (OR: 0.85; 95% CIs: 0.72-0.99). Physical inactivity mediated the association between exercising alters and obesity. Ancillary analyses showed that having exercising alters in the neighborhood compared to other locations tended to reduce the odds of obesity. This work demonstrates the importance of social networks among older adults in facilitating a physically active lifestyle and reducing the odds of obesity. Such findings can inform the design of public health interventions that seek to improve the environmental conditions supporting the physical

  19. Physical inactivity mediates the association between the perceived exercising behavior of social network members and obesity: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Janette S Leroux

    Full Text Available Social networks influence the spread of depression, health behaviors, and obesity. The social networks of older urban-dwelling adults were examined to assess whether physical inactivity mediated the association between social networks and obesity.Data come from the Montreal Neighborhood Networks and Healthy Aging study (n=2707. Self-reported height and weight were used to calculate body mass index (BMI with obesity defined as a BMI ≥ 30. A name generator/interpreter instrument was used to elicit participants' core ties (i.e., alters, and assess whether alters exercised regularly and resided in participants' neighborhoods. The International Physical Activity Questionnaire was used to measure physical inactivity. Separate multilevel logistic regression analyses were conducted for younger (18-54 years and older (55 years plus age groups to examine the association between the exercising behavior of alters and obesity. Ancillary analyses examined whether the residential location of alters was associated with obesity. Mediation analyses assessed whether physical inactivity mediated the association between alter exercising behavior and obesity. Models adjusted for participant socio-demographic and -economic characteristics.Among the older age stratum (55 years plus, physically inactive individuals were more likely obese (OR 2.14; 95% CIs: 1.48-3.10; participants who had more exercising alters were less likely obese (OR: 0.85; 95% CIs: 0.72-0.99. Physical inactivity mediated the association between exercising alters and obesity. Ancillary analyses showed that having exercising alters in the neighborhood compared to other locations tended to reduce the odds of obesity.This work demonstrates the importance of social networks among older adults in facilitating a physically active lifestyle and reducing the odds of obesity. Such findings can inform the design of public health interventions that seek to improve the environmental conditions supporting the

  20. The Associations Between Socioeconomic Status and Lifestyle Factors in European Adolescents: A Population-based Study

    Directory of Open Access Journals (Sweden)

    Novak Dario

    2017-11-01

    Full Text Available The main purpose of the present study was to determine the associations between socioeconomic status (SES and lifestyle factors. In this cross-sectional study, participants were 3,072 adolescents from two European countries of Lithuania and Serbia. The dependent variable was SES, while independent variables were gender, adherence to a Mediterranean diet, body-mass index, self-rated health, psychological distress, moderate-to-vigorous physical activity and sedentary behaviour. The associations between dependent and independent variables were analysed by using logistic regression analysis. In univariate model, middle/high SES was associated with higher adherence to a Mediterranean diet (ptrend = 0.003, good self-rated health (OR 1.51; 95 % CI 1.12 to 2.05 and meeting recommendations of moderate-to-vigorous physical activity (OR 2.09; 95 % CI 1.45 to 3.00, yet inversely associated with psychological distress (OR 0.81; 95 % CI 0.66 to 0.99 and sedentary behaviour (OR 0.80; 95 % CI 0.68 to 0.94. No associations were found between SES and bodymass index and gender. In multivariate model, the same associations occurred between middle/high SES and lifestyle factors. In conclusion, special strategies and policies, based on more affordable nutrition and participation in moderate-to-vigorous physical activity, should be implemented within the system.

  1. Study of the type of gamma radioactivity in platform carbonaceous rocks: analyses and environmental, diagenetic and geodynamical interpretations

    International Nuclear Information System (INIS)

    Raddadi, Mohamed-Chaker

    2004-01-01

    In well-logging, values of gamma-activity are measured by scintillometry. A conventional paradigm is to link high γ-activity to Potassium (K) and Thorium (Th) isotopes present in clays and to Uranium isotopes present either in detrital sediments (typically in zircon or monazite minerals) or to sediments rich in organic matter. In shallow-water carbonates platforms, high γ-activities are interpreted in the same way. However, in a first γ-scintillometer survey of the Gorges du Nan section (sub-alpine Vercors massif), we found inconsistencies between lithologies and their expected γ-responses: the highest radioactive beds do not correspond to high argillaceous or detrital limestones and marls, but to some low content argillaceous or 'pure' limestones beds. The aim of this study was to identify the radioactive isotopes associated to different types of carbonates, their localisation, their abundance and their respective contribution to the total gamma response in order to propose a new method for the interpretation of gamma-ray logs in shallow-water carbonates. This study was focused on two intervals: - The first one corresponds to the Ba3 depositional sequence (Upper Barremian) which is composed essentially of limestones. This sequence was studied in the Vercors and Chartreuse sub-alpine massifs near Grenoble and in the Swiss Jura near Neuchatel; - The second one corresponds to the 'Lower Oritolina marls' interval. This interval was studied in the Vercors and Chartreuse sub-alpine massifs near Grenoble, in Spain (Organya basin) and in central Tunisia near Kairouan. We carried out detailed sedimentological, diagenetic and isotopic studies of all these sections. Oxygen and carbon stable isotopes analyses allowed us to establish some large scale correlations between sections in the French Alps, in the Pyrenees and in central Tunisia. The good correlation between Oxygen and Carbon stable isotopes curves of the Lower Orbitolina marls in all the

  2. INS VNTR is not associated with childhood obesity in 1,023 families: a family-based study.

    Science.gov (United States)

    Bouatia-Naji, Nabila; De Graeve, Franck; Brönner, Günter; Lecoeur, Cécile; Vatin, Vincent; Durand, Emmanuelle; Lichtner, Peter; Nguyen, Thuy T; Heude, Barbara; Weill, Jacques; Lévy-Marchal, Claire; Hebebrand, Johannes; Froguel, Philippe; Meyre, David

    2008-06-01

    Previous studies have described genetic associations of the insulin gene variable number tandem repeat (INS VNTR) variant with childhood obesity and associated phenotypes. We aimed to assess the contribution of INS VNTR genotypes to childhood obesity and variance of insulin resistance, insulin secretion, and birth weight using family-based design. Participants were either French or German whites. We used transmission disequilibrium tests (TDTs) for assessing binary traits and quantitative pedigree disequilibrium tests for assessing continuous traits. In contrast to previous findings, we did not observe any familial association with childhood obesity (T = 50%, P = 0.77) in the 1,023 families tested. In French obese children, INS VNTR did not associate with fasting insulin levels (P = 0.23) and class I allele showed only borderline association with increased insulin secretion index at 30 min (P = 0.03). INS VNTR did not associate with birth weight in obese children (P = 0.98) and TDT analyses in 350 French families with history of low birth weight (LBW) showed no association with this condition (P = 0.92). In summary, our study, the largest performed so far, does not support the previously reported associations between INS VNTR and childhood obesity, insulin resistance, or birth weight, and does not suggest any major role for this variant in modulating these traits.

  3. Physical Activity, Study Sitting Time, Leisure Sitting Time, and Sleep Time Are Differently Associated With Obesity in Korean Adolescents: A Population-Based Study.

    Science.gov (United States)

    Kong, Il Gyu; Lee, Hyo-Jeong; Kim, So Young; Sim, Songyong; Choi, Hyo Geun

    2015-11-01

    Low physical activity, long leisure sitting time, and short sleep time are risk factors for obesity, but the association with study sitting time is unknown. The objective of this study was to evaluate the association between these factors and obesity.We analyzed the association between physical activity, study sitting time, leisure sitting time, and sleep time and subject weight (underweight, healthy weight, overweight, and obese), using data from a large population-based survey, the 2013 Korea Youth Risk Behavior Web-based Survey. Data from 53,769 participants were analyzed using multinomial logistic regression analyses with complex sampling. Age, sex, region of residence, economic level, smoking, stress level, physical activity, sitting time for study, sitting time for leisure, and sleep time were adjusted as the confounders.Low physical activity (adjusted odds ratios [AORs] = 1.03, 1.12) and long leisure sitting time (AORs = 1.15, 1.32) were positively associated with overweight and obese. Low physical activity (AOR = 1.33) and long leisure sitting time (AOR = 1.12) were also associated with underweight. Study sitting time was negatively associated with underweight (AOR = 0.86) but was unrelated to overweight (AOR = 0.97, 95% confidence interval [CI] = 0.91-1.03) and obese (AOR = 0.94, 95% CI = 0.84-1.04). Sleep time (physical activity, decreasing leisure sitting time, and obtaining sufficient sleep would be beneficial in maintaining a healthy weight. However, study sitting time was not associated with overweight or obese.

  4. Cost-of-illness studies and cost-effectiveness analyses in anxiety disorders: a systematic review.

    Science.gov (United States)

    Konnopka, Alexander; Leichsenring, Falk; Leibing, Eric; König, Hans-Helmut

    2009-04-01

    To review cost-of-illness studies (COI) and cost-effectiveness analyses (CEA) conducted for anxiety disorders. Based on a database search in Pubmed, PsychINFO and NHS EED, studies were classified according to various criteria. Cost data were inflated and converted to 2005 US-$ purchasing power parities (PPP). We finally identified 20 COI and 11 CEA of which most concentrated on panic disorder (PD) and generalized anxiety disorder (GAD). Differing inclusion of cost categories limited comparability of COI. PD and GAD tended to show higher direct costs per case, but lower direct cost per inhabitant than social and specific phobias. Different measures of effectiveness severely limited comparability of CEA. Overall CEA analysed 26 therapeutic or interventional strategies mostly compared to standard treatment, 8 of them resulting in lower better effectiveness and costs than the comparator. Anxiety disorders cause considerable costs. More research on phobias, more standardised inclusion of cost categories in COI and a wider use of comparable effectiveness measures (like QALYs) in CEA is needed.

  5. Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.

    Directory of Open Access Journals (Sweden)

    Roman Pfister

    2011-10-01

    Full Text Available Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP levels in blood and risk of type 2 diabetes (T2D, but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36% decreased risk of incident T2D per one standard deviation (SD higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97 was similar to that expected (0.96, 0.93-0.98 based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90 and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29 per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies

  6. Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study

    DEFF Research Database (Denmark)

    Blahak, C; Baezner, H; Pantoni, L

    2009-01-01

    non-disabled individuals with reported falls was analysed, using the cross sectional data of the Leukoaraiosis and Disability (LADIS) study. Detailed anatomical distributions of ARWMC assessed by MRI studies were analysed with respect to falls and balance performance. RESULTS: The severity of global...... ARWMC was significantly associated with a history of falls in the year prior to study inclusion (22.2% in the mild, 31.6% in the moderate and 37.3% in the severe ARWMC group according to the Fazekas scale; p = 0.002). Analysing the anatomical distribution of ARWMC, using the semiquantitative Scheltens...

  7. Associations between children's social functioning and physical activity participation are not mediated by social acceptance: a cross-sectional study.

    Science.gov (United States)

    Sebire, Simon J; Jago, Russell; Fox, Kenneth R; Page, Angie S; Brockman, Rowan; Thompson, Janice L

    2011-09-30

    Physical activity (PA) during childhood often occurs in social contexts. As such, children's ability to develop and maintain friendship groups may be important in understanding their PA. This paper investigates the associations among children's social functioning, and physical activity and whether perceptions of social acceptance mediate any social functioning-PA association. A cross sectional survey in which 652 10-11 year olds self-reported their peer (e.g. difficulties with friends) and conduct (e.g. anger/aggression) problems, prosocial behaviours (e.g. being kind to others) and perceptions of social acceptance. Physical activity was objectively assessed by Actigraph GT1M accelerometers to estimate counts per minute, (CPM) and minutes of moderate-to-vigorous physical activity (MVPA). Linear regression analyses were conducted to investigate associations between social functioning and PA. Indirect effects were analysed to explore mediation by social acceptance. Among boys, peer problems were negatively associated with CPM and MVPA and conduct problems were positively associated with CPM and MVPA. Prosocial behaviour was unrelated to PA in boys. Social functioning was not associated with PA among girls. Social acceptance did not mediate the social functioning-PA relationship. Boys' conduct and peer problems were associated positively and negatively respectively with their PA but this relationship was not mediated by perceptions of social acceptance. Future research should study alternative mediators to understand the processes underpinning this relationship.

  8. Genomewide Association Scan of a Mortality Associated Endophenotype for a Long and Healthy Life in the Long Life Family Study.

    Science.gov (United States)

    Singh, Jatinder; Minster, Ryan L; Schupf, Nicole; Kraja, Aldi; Liu, YongMei; Christensen, Kaare; Newman, Anne B; Kammerer, Candace M

    2017-10-01

    Identification of genes or fundamental biological pathways that regulate aging phenotypes and longevity could lead to possible interventions to increase healthy longevity. Using data from the Long Life Family Study, we performed genomewide association analyses on an endophenotype construct, LF1, comprising a linear combination of traits across health domains. LF1 primarily reflected traits from the pulmonary and physical activity domains. We detected a significant association between LF1 and a locus on chromosome 10p15 (p-value = 4.65 × 10-8) and suggestive evidence (p-value physical function domains may be located on chromosome 1p13 near the NBPF6 locus. Further investigation of this possible locus and other suggestive loci may reveal novel biological pathways that influence healthy aging. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Genome-wide association of lipid-lowering response to statins in combined study populations.

    Directory of Open Access Journals (Sweden)

    Mathew J Barber

    2010-03-01

    Full Text Available Statins effectively lower total and plasma LDL-cholesterol, but the magnitude of decrease varies among individuals. To identify single nucleotide polymorphisms (SNPs contributing to this variation, we performed a combined analysis of genome-wide association (GWA results from three trials of statin efficacy.Bayesian and standard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglyceride on a total of 3932 subjects using data from three studies: Cholesterol and Pharmacogenetics (40 mg/day simvastatin, 6 weeks, Pravastatin/Inflammation CRP Evaluation (40 mg/day pravastatin, 24 weeks, and Treating to New Targets (10 mg/day atorvastatin, 8 weeks. Genotype imputation was used to maximize genomic coverage and to combine information across studies. Phenotypes were normalized within each study to account for systematic differences among studies, and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies. Two SNP associations were assessed as having posterior probability greater than 50%, indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response. SNP rs8014194, located within the CLMN gene on chromosome 14, was strongly associated with statin-mediated change in total cholesterol with an 84% probability by Bayesian analysis, and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis (P = 1.8 x 10(-8. This SNP was less significantly associated with change in LDL-cholesterol (posterior probability = 0.16, P = 4.0 x 10(-6. Bayesian analysis also assigned a 51% probability that rs4420638, located in APOC1 and near APOE, was associated with change in LDL-cholesterol.Using combined GWA analysis from three clinical trials involving nearly 4,000 individuals treated with simvastatin, pravastatin, or atorvastatin, we

  10. Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

    Directory of Open Access Journals (Sweden)

    Vesna Boraska

    Full Text Available Brachial circumference (BC, also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05 in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.

  11. Factors associated with generic health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD): a cross-sectional study.

    Science.gov (United States)

    Brandl, Magdalena; Böhmer, Merle M; Brandstetter, Susanne; Finger, Tamara; Fischer, Wiebke; Pfeifer, Michael; Apfelbacher, Christian

    2018-02-01

    Health-related quality of life (HRQOL) is impaired in chronic obstructive pulmonary disease (COPD) patients, but determining factors for HRQOL are still not unequivocal. This study measures HRQOL among patients with COPD and aims to determine factors associated with HRQOL. Data for cross-sectional analyses were obtained from the baseline of a cohort study. The study population includes adult COPD patients (disease duration ≥3 months), recruited from primary and secondary care settings in Germany, without acute psychiatric/neurologic disease (exception: affective/ anxiety disorders). HRQOL was assessed using the Short-Form 12 (SF-12) Health Survey Questionnaire, comprising a physical and mental component. Independent variables encompass socio-demographic, disease-specific, treatment-related and psychological factors. Multivariable linear regression analyses were conducted. In total, 206 COPD patients (60.7% male; mean age: 65.3 years) took part in the study. In multivariable analysis, the physical component score showed a significant negative association with the COPD Assessment Test (CAT) (PCOPD.

  12. Association between Habitual Dietary Salt Intake and Risk of Gastric Cancer: A Systematic Review of Observational Studies

    Directory of Open Access Journals (Sweden)

    Sheng Ge

    2012-01-01

    Full Text Available Purpose. Systematic reviews of case-control and prospective studies showed a positive association between habitual salt intake and gastric cancer. Given new studies published thereafter, we carried out a meta-analysis to assess the association between dietary salt intake and gastric cancer. Methods. Case-control studies and cohort studies published between January 1992 and January 2012 on PubMed and Embase were searched. We quantified associations between salt intake and gastric cancer with meta-analysis. Results. Eleven studies (7 case controls and 4 cohorts finally were included in the meta-analysis (total population: n=2076498; events: n=12039. The combined odds ratio showed significantly positive association between high salt intake and gastric cancer compared with low salt intake (OR = 2.05, 95% CI [1.60, 2.62]; P<0.00001. In subgroup meta-analysis, findings were slightly different when analyses were restricted to salty food intake (OR = 2.41, 95% CI [2.08, 2.78]; P<0.00001 as well as in Asia (OR = 1.27 95% CI [1.22, 1.32]; P<0.00001. There was no evidence that sample size, exposure assessment substantially influenced the estimate of effects. Conclusions. The systemic review supports the hypothesis that dietary salt intake is positively associated with the risk of gastric cancer.

  13. First study of correlation between oleic acid content and SAD gene polymorphism in olive oil samples through statistical and bayesian modeling analyses.

    Science.gov (United States)

    Ben Ayed, Rayda; Ennouri, Karim; Ercişli, Sezai; Ben Hlima, Hajer; Hanana, Mohsen; Smaoui, Slim; Rebai, Ahmed; Moreau, Fabienne

    2018-04-10

    Virgin olive oil is appreciated for its particular aroma and taste and is recognized worldwide for its nutritional value and health benefits. The olive oil contains a vast range of healthy compounds such as monounsaturated free fatty acids, especially, oleic acid. The SAD.1 polymorphism localized in the Stearoyl-acyl carrier protein desaturase gene (SAD) was genotyped and showed that it is associated with the oleic acid composition of olive oil samples. However, the effect of polymorphisms in fatty acid-related genes on olive oil monounsaturated and saturated fatty acids distribution in the Tunisian olive oil varieties is not understood. Seventeen Tunisian olive-tree varieties were selected for fatty acid content analysis by gas chromatography. The association of SAD.1 genotypes with the fatty acids composition was studied by statistical and Bayesian modeling analyses. Fatty acid content analysis showed interestingly that some Tunisian virgin olive oil varieties could be classified as a functional food and nutraceuticals due to their particular richness in oleic acid. In fact, the TT-SAD.1 genotype was found to be associated with a higher proportion of mono-unsaturated fatty acids (MUFA), mainly oleic acid (C18:1) (r = - 0.79, p SAD.1 association with the oleic acid composition of olive oil was identified among the studied varieties. This correlation fluctuated between studied varieties, which might elucidate variability in lipidic composition among them and therefore reflecting genetic diversity through differences in gene expression and biochemical pathways. SAD locus would represent an excellent marker for identifying interesting amongst virgin olive oil lipidic composition.

  14. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants

    Science.gov (United States)

    Juran, Brian D.; Hirschfield, Gideon M.; Invernizzi, Pietro; Atkinson, Elizabeth J.; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M.; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L.; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E. Jenny; Mason, Andrew L.; Myers, Robert P.; Milkiewicz, Piotr; Odin, Joseph A.; Luketic, Velimir A.; Bacon, Bruce R.; Bodenheimer, Henry C.; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K.; Bossa, Fabrizio; Gershwin, M. Eric; deAndrade, Mariza; Amos, Christopher I.; Lazaridis, Konstantinos N.; Seldin, Michael F.; Siminovitch, Katherine A.

    2012-01-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies. PMID:22936693

  15. Association study of ghrelin receptor gene polymorphisms in rheumatoid arthritis.

    Science.gov (United States)

    Robledo, G; Rueda, B; Gonzalez-Gay, M A; Fernández, B; Lamas, J R; Balsa, A; Pascual-Salcedo, D; García, A; Raya, E; Martín, J

    2010-01-01

    Ghrelin is a newly characterised growth hormone (GH) releasing peptide widely distributed that may play an important role in the regulation of metabolic balance in inflammatory diseases such as rheumatoid arthritis (RA) by decreasing the pro-inflammatory Th1 responses. In this study we investigated the possible contribution of several polymorphisms in the functional Ghrelin receptor to RA susceptibility. A screening of 3 single nucleotide polymorphisms (SNPs) was performed in a total of 950 RA patients and 990 healthy controls of Spanish Caucasian origin. Genotyping of all 3 SNPs was performed by real-time polymerase chain reaction technology, using the TaqMan 5'-allele discrimination assay. We observed no statistically significant deviation between RA patients and controls for the GHSR SNPs analysed. In addition, we performed a haplotype analysis that did not reveal an association with RA susceptibility. The stratification analysis for the presence of shared epitope (SE), rheumatoid factor (RF) or antibodies anti cyclic citrullinated peptide (anti-CCP) did not detect significant association of the GHSR polymorphisms with RA. These findings suggest that the GHSR gene polymorphisms do not appear to play a major role in RA genetic predisposition in our population.

  16. Genome-wide association study of Lp-PLA(2 activity and mass in the Framingham Heart Study.

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    Sunil Suchindran

    2010-04-01

    Full Text Available Lipoprotein-associated phospholipase A(2 (Lp-PLA(2 is an emerging risk factor and therapeutic target for cardiovascular disease. The activity and mass of this enzyme are heritable traits, but major genetic determinants have not been explored in a systematic, genome-wide fashion. We carried out a genome-wide association study of Lp-PLA(2 activity and mass in 6,668 Caucasian subjects from the population-based Framingham Heart Study. Clinical data and genotypes from the Affymetrix 550K SNP array were obtained from the open-access Framingham SHARe project. Each polymorphism that passed quality control was tested for associations with Lp-PLA(2 activity and mass using linear mixed models implemented in the R statistical package, accounting for familial correlations, and controlling for age, sex, smoking, lipid-lowering-medication use, and cohort. For Lp-PLA(2 activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6 x 10(-24; CELSR2/PSRC1 on chromosome 1 (p = 3 x 10(-15; SCARB1 on chromosome 12 (p = 1x10(-8 and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4 x 10(-8. All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA(2 mass, 12 SNPs achieved genome-wide significance, all clustering in a region on chromosome 6p12.3 near the PLA2G7 gene. Our analyses demonstrate that genetic polymorphisms may contribute to inter-individual variation in Lp-PLA(2 activity and mass.

  17. Mitochondrial genomics and antiretroviral therapy-associated metabolic complications in HIV-infected Black South Africans: a pilot study.

    Science.gov (United States)

    Sinxadi, Phumla Z; Dave, Joel A; Samuels, David C; Heckmann, Jeannine M; Maartens, Gary; Levitt, Naomi S; Wester, C William; Haas, David W; Hulgan, Todd

    2013-07-01

    Studies suggest that mitochondrial DNA (mtDNA) haplogroups are associated with antiretroviral therapy (ART)-related metabolic complications and distal sensory polyneuropathy (DSP), but there have been few studies in persons of African descent. We explored such associations in South African adults. Clinical and laboratory data and DNA specimens from a cross-sectional study were used. Sequencing and Phylotree determined African mtDNA subhaplogroups. Wilcoxon and regression analyses determined associations between mtDNA subhaplogroups and ART-related complications. The 171 participants represented six major haplogroups: L0 (n=78), L1 (n=3), L2 (n=30), L3 (n=53), L4 (n=1), and L5 (n=6). Analyses were restricted to 161 participants representing L0, L2, and L3: 78% were female; the median age was 36 years. All had been exposed to thymidine analogues, 42% were on lopinavir/ritonavir (lopinavir/r), and 58% were on either efavirenz or nevirapine. Median (IQR) ART duration was 22 (14-36) months. Median fasting triglycerides were 1.60 (1.13-1.75) and 1.04 (0.83-1.45) mmol/liter among L3e1 (n=22) and other subhaplogroups, respectively (p=0.003). Subhaplogroup L3e1 [adjusted OR (aOR) 3.16 (95% CI: 1.11-8.96); p=0.03] and exposure to lopinavir/r [aOR 2.98 (95% CI: 1.02-8.96); p=0.05] were independently associated with hypertriglyceridemia, after adjusting for age, sex, and ART duration. There were no significant associations between mtDNA haplogroups and cholesterol, dysglycemia, hyperlactatemia, or lipoatrophy, or DSP. Subhaplogroup L3e1 and lopinavir/r exposure were independently associated with hypertriglyceridemia in black South Africans on ART. This is the first report to link an African mtDNA variant with hypertriglyceridemia. If replicated, these findings may provide new insights into host factors affecting metabolic complications.

  18. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population.

    Science.gov (United States)

    Palomba, Grazia; Loi, Angela; Porcu, Eleonora; Cossu, Antonio; Zara, Ilenia; Budroni, Mario; Dei, Mariano; Lai, Sandra; Mulas, Antonella; Olmeo, Nina; Ionta, Maria Teresa; Atzori, Francesco; Cuccuru, Gianmauro; Pitzalis, Maristella; Zoledziewska, Magdalena; Olla, Nazario; Lovicu, Mario; Pisano, Marina; Abecasis, Gonçalo R; Uda, Manuela; Tanda, Francesco; Michailidou, Kyriaki; Easton, Douglas F; Chanock, Stephen J; Hoover, Robert N; Hunter, David J; Schlessinger, David; Sanna, Serena; Crisponi, Laura; Palmieri, Giuseppe

    2015-05-10

    Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p <  0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.

  19. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

    International Nuclear Information System (INIS)

    Palomba, Grazia; Loi, Angela; Porcu, Eleonora; Cossu, Antonio; Zara, Ilenia

    2015-01-01

    Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10 −6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10 −5 , we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10 −5 ), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population. The online version of this article (doi:10.1186/s12885-015-1392-9) contains supplementary material, which is available to authorized users

  20. Dietary factors associated with obesity indicators and level of sports participation in Flemish adults: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Delecluse Christophe

    2007-09-01

    Full Text Available Abstract Background Obesity develops when energy intake continuously exceeds energy expenditure, causing a fundamental chronic energy imbalance. Societal and behavioural changes over the last decades are held responsible for the considerable increase in sedentary lifestyles and inappropriate dietary patterns. The role of dietary fat and other dietary factors in the aetiology and maintenance of excess weight is controversial. The purposes of the present study were to investigate the dietary factors associated with body mass index (BMI and waist circumference (WC, and to analyse whether dietary intake varies between subjects with different levels of sports participation. Methods Data for this cross-sectional study, including anthropometric measurements, 3-day diet diary and physical activity questionnaire, were collected by the Flemish Policy Research Centre Sport, Physical Activity and Health (SPAH between October 2002 and April 2004. Results of 485 adult men and 362 women with plausible dietary records were analysed. Analyses of covariance were performed to determine the differences in dietary intake between normal weight, overweight and obese subjects, and between subjects with different levels of sports participation. Results Total energy intake, protein and fat intake (kcal/day were significantly higher in obese subjects compared to their lean counterparts in both genders. Percentage of energy intake from fat was significantly higher in obese men compared to men with normal weight or WC. Energy percentages from carbohydrates and fibres were negatively related to BMI and WC in men, whereas in women a higher carbohydrate and fibre intake was positively associated with obesity. Alcohol intake was positively associated with WC in men. Subjects participating in health related sports reported higher intake of carbohydrates, but lower intake of fat compared to subjects not participating in sports. Conclusion This study supports the evidence that

  1. Risk and Protective Factors for Intimate Partner Violence Against Women: Systematic Review and Meta-analyses of Prospective-Longitudinal Studies.

    Science.gov (United States)

    Yakubovich, Alexa R; Stöckl, Heidi; Murray, Joseph; Melendez-Torres, G J; Steinert, Janina I; Glavin, Calla E Y; Humphreys, David K

    2018-07-01

    The estimated lifetime prevalence of physical or sexual intimate partner violence (IPV) is 30% among women worldwide. Understanding risk and protective factors is essential for designing effective prevention strategies. To quantify the associations between prospective-longitudinal risk and protective factors and IPV and identify evidence gaps. We conducted systematic searches in 16 databases including MEDLINE and PsycINFO from inception to June 2016. The study protocol is registered with PROSPERO (CRD42016039213). We included published and unpublished studies available in English that prospectively analyzed any risk or protective factor(s) for self-reported IPV victimization among women and controlled for at least 1 other variable. Three reviewers were involved in study screening. One reviewer extracted estimates of association and study characteristics from each study and 2 reviewers independently checked a random subset of extractions. We assessed study quality with the Cambridge Quality Checklists. When studies investigated the same risk or protective factor using similar measures, we computed pooled odds ratios (ORs) by using random-effects meta-analyses. We summarized heterogeneity with I 2 and τ 2 . We synthesized all estimates of association, including those not meta-analyzed, by using harvest plots to illustrate evidence gaps and trends toward negative or positive associations. Of 18 608 studies identified, 60 were included and 35 meta-analyzed. Most studies were based in the United States. The strongest evidence for modifiable risk factors for IPV against women were unplanned pregnancy (OR = 1.66; 95% confidence interval [CI] = 1.20, 1.31) and having parents with less than a high-school education (OR = 1.55; 95% CI = 1.10, 2.17). Being older (OR = 0.96; 95% CI = 0.93, 0.98) or married (OR = 0.93; 95% CI = 0.87, 0.99) were protective. To our knowledge, this is the first systematic, meta-analytic review of all risk and

  2. Visiting green space is associated with mental health and vitality: A cross-sectional study in four european cities.

    Science.gov (United States)

    van den Berg, Magdalena; van Poppel, Mireille; van Kamp, Irene; Andrusaityte, Sandra; Balseviciene, Birute; Cirach, Marta; Danileviciute, Asta; Ellis, Naomi; Hurst, Gemma; Masterson, Daniel; Smith, Graham; Triguero-Mas, Margarita; Uzdanaviciute, Inga; de Wit, Puck; van Mechelen, Willem; Gidlow, Christopher; Grazuleviciene, Regina; Nieuwenhuijsen, Mark J; Kruize, Hanneke; Maas, Jolanda

    2016-03-01

    Many epidemiological studies have found that people living in environments with more green space report better physical and mental health than those with less green space. However, the association between visits to green space and mental health has seldom been studied. The current study explored the associations between time spent in green spaces by purposeful visits and perceived mental health and vitality in four different European cities, and to what extent gender, age, level of education, attitude towards nature and childhood nature experience moderate these associations. Data was gathered using a questionnaire administered in four European cities (total n=3748). Multilevel analyses showed significant positive associations between time spent visiting green spaces and mental health and vitality in the pooled data, as well as across the four cities. Significant effect modification was found for level of education and childhood nature experience. The findings confirm the hypothesis that more time spent in green space is associated with higher scores on mental health and vitality scales, independent of cultural and climatic contexts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Scleral topography analysed by optical coherence tomography.

    Science.gov (United States)

    Bandlitz, Stefan; Bäumer, Joachim; Conrad, Uwe; Wolffsohn, James

    2017-08-01

    A detailed evaluation of the corneo-scleral-profile (CSP) is of particular relevance in soft and scleral lenses fitting. The aim of this study was to use optical coherence tomography (OCT) to analyse the profile of the limbal sclera and to evaluate the relationship between central corneal radii, corneal eccentricity and scleral radii. Using OCT (Optos OCT/SLO; Dunfermline, Scotland, UK) the limbal scleral radii (SR) of 30 subjects (11M, 19F; mean age 23.8±2.0SD years) were measured in eight meridians 45° apart. Central corneal radii (CR) and corneal eccentricity (CE) were evaluated using the Oculus Keratograph 4 (Oculus, Wetzlar, Germany). Differences between SR in the meridians and the associations between SR and corneal topography were assessed. Median SR measured along 45° (58.0; interquartile range, 46.8-84.8mm) was significantly (ptopography and may provide additional data useful in fitting soft and scleral contact lenses. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  4. A review of multivariate analyses in imaging genetics

    Directory of Open Access Journals (Sweden)

    Jingyu eLiu

    2014-03-01

    Full Text Available Recent advances in neuroimaging technology and molecular genetics provide the unique opportunity to investigate genetic influence on the variation of brain attributes. Since the year 2000, when the initial publication on brain imaging and genetics was released, imaging genetics has been a rapidly growing research approach with increasing publications every year. Several reviews have been offered to the research community focusing on various study designs. In addition to study design, analytic tools and their proper implementation are also critical to the success of a study. In this review, we survey recent publications using data from neuroimaging and genetics, focusing on methods capturing multivariate effects accommodating the large number of variables from both imaging data and genetic data. We group the analyses of genetic or genomic data into either a prior driven or data driven approach, including gene-set enrichment analysis, multifactor dimensionality reduction, principal component analysis, independent component analysis (ICA, and clustering. For the analyses of imaging data, ICA and extensions of ICA are the most widely used multivariate methods. Given detailed reviews of multivariate analyses of imaging data available elsewhere, we provide a brief summary here that includes a recently proposed method known as independent vector analysis. Finally, we review methods focused on bridging the imaging and genetic data by establishing multivariate and multiple genotype-phenotype associations, including sparse partial least squares, sparse canonical correlation analysis, sparse reduced rank regression and parallel ICA. These methods are designed to extract latent variables from both genetic and imaging data, which become new genotypes and phenotypes, and the links between the new genotype-phenotype pairs are maximized using different cost functions. The relationship between these methods along with their assumptions, advantages, and

  5. Marker-trait association study for protein content in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Jadhav, A A; Rayate, S J; Mhase, L B; Thudi, M; Chitikineni, A; Harer, P N; Jadhav, A S; Varshney, R K; Kulwal, P L

    2015-06-01

    Chickpea (Cicer arietinum L.) is the second most important cool season food legume cultivated in arid and semiarid regions of the world. The objective of the present study was to study variation for protein content in chickpea germplasm, and to find markers associated with it. A set of 187 genotypes comprising both international and exotic collections, and representing both desi and kabuli types with protein content ranging from 13.25% to 26.77% was used. Twenty-three SSR markers representing all eight linkage groups (LG) amplifying 153 loci were used for the analysis. Population structure analysis identified three subpopulations, and corresponding Q values of principal components were used to take care of population structure in the analysis which was performed using general linear and mixed linear models. Marker-trait association (MTA) analysis identified nine significant associations representing four QTLs in the entire population. Subpopulation analyses identified ten significant MTAs representing five QTLs, four of which were common with that of the entire population. Two most significant QTLs linked with markers TR26.205 and CaM1068.195 were present on LG3 and LG5. Gene ontology search identified 29 candidate genes in the region of significant MTAs on LG3. The present study will be helpful in concentrating on LG3 and LG5 for identification of closely linked markers for protein content in chickpea and for their use in molecular breeding programme for nutritional quality improvement.

  6. A Genome Wide Association Study Links Glutamate Receptor Pathway to Sporadic Creutzfeldt-Jakob Disease Risk

    Science.gov (United States)

    Sanchez-Juan, Pascual; Bishop, Matthew T.; Kovacs, Gabor G.; Calero, Miguel; Aulchenko, Yurii S.; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Ángel; van der Lee, Sven J.; Ströbel, Thomas; Rivadeneira, Fernando; Hofman, Albert; Haïk, Stéphane; Combarros, Onofre; Berciano, José; Uitterlinden, Andre G.; Collins, Steven J.; Budka, Herbert; Brandel, Jean-Philippe; Laplanche, Jean Louis; Pocchiari, Maurizio; Zerr, Inga; Knight, Richard S. G.; Will, Robert G.; van Duijn, Cornelia M.

    2015-01-01

    We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis. PMID:25918841

  7. Age and gender effects on normal regional cerebral blood flow studied using two different voxel-based statistical analyses

    International Nuclear Information System (INIS)

    Pirson, A.S.; George, J.; Krug, B.; Vander Borght, T.; Van Laere, K.; Jamart, J.; D'Asseler, Y.; Minoshima, S.

    2009-01-01

    Fully automated analysis programs have been applied more and more to aid for the reading of regional cerebral blood flow SPECT study. They are increasingly based on the comparison of the patient study with a normal database. In this study, we evaluate the ability of Three-Dimensional Stereotactic Surface Projection (3 D-S.S.P.) to isolate effects of age and gender in a previously studied normal population. The results were also compared with those obtained using Statistical Parametric Mapping (S.P.M.99). Methods Eighty-nine 99m Tc-E.C.D.-SPECT studies performed in carefully screened healthy volunteers (46 females, 43 males; age 20 - 81 years) were analysed using 3 D-S.S.P.. A multivariate analysis based on the general linear model was performed with regions as intra-subject factor, gender as inter-subject factor and age as co-variate. Results Both age and gender had a significant interaction effect with regional tracer uptake. An age-related decline (p < 0.001) was found in the anterior cingulate gyrus, left frontal association cortex and left insula. Bilateral occipital association and left primary visual cortical uptake showed a significant relative increase with age (p < 0.001). Concerning the gender effect, women showed higher uptake (p < 0.01) in the parietal and right sensorimotor cortices. An age by gender interaction (p < 0.01) was only found in the left medial frontal cortex. The results were consistent with those obtained with S.P.M.99. Conclusion 3 D-S.S.P. analysis of normal r.C.B.F. variability is consistent with the literature and other automated voxel-based techniques, which highlight the effects of both age and gender. (authors)

  8. The association between obesity and back pain in nine countries: a cross-sectional study.

    Science.gov (United States)

    Koyanagi, Ai; Stickley, Andrew; Garin, Noe; Miret, Marta; Ayuso-Mateos, Jose Luis; Leonardi, Matilde; Koskinen, Seppo; Galas, Aleksander; Haro, Josep Maria

    2015-02-11

    The association between obesity and back pain has mainly been studied in high-income settings with inconclusive results, and data from older populations and developing countries are scarce. The aim of this study was to assess this association in nine countries in Asia, Africa, Europe, and Latin America among older adults using nationally-representative data. Data on 42116 individuals ≥50 years who participated in the Collaborative Research on Ageing in Europe (COURAGE) study conducted in Finland, Poland, and Spain in 2011-2012, and the World Health Organization's Study on Global Ageing and Adult Health (SAGE) conducted in China, Ghana, India, Mexico, Russia, and South Africa in 2007-2010 were analysed. Information on measured height and weight available in the two datasets was used to calculate Body Mass Index (BMI). Self-reported back pain occurring in the past 30 days was the outcome. Multivariable logistic regression analysis was used to assess the association between BMI and back pain. The prevalence of back pain ranged from 21.5% (China) to 57.5% (Poland). In the multivariable analysis, compared to BMI 18.5-24.9 kg/m(2), significantly higher odds for back pain were observed for BMI ≥35 kg/m(2) in Finland (OR 3.33), Russia (OR 2.20), Poland (OR 2.03), Spain (OR 1.56), and South Africa (OR 1.48); BMI 30.0-34.0 kg/m(2) in Russia (OR 2.76), South Africa (OR 1.51), and Poland (OR 1.47); and BMI 25.0-29.9 kg/m(2) in Russia (OR 1.51) and Poland (OR 1.40). No significant associations were found in the other countries. The strength of the association between obesity and back pain may vary by country. Future studies are needed to determine the factors contributing to differences in the associations observed.

  9. The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4,610 cases amongst 18,637 participants.

    Directory of Open Access Journals (Sweden)

    Debbie A Lawlor

    Full Text Available BACKGROUND: It is unclear whether C-reactive protein (CRP is causally related to coronary heart disease (CHD. Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864 and CHD risk in the largest study to date of this association. METHODS AND RESULTS: We estimated the association of CRP genetic variant +1444C>T (rs1130864 with CRP levels and with CHD in five studies and then pooled these analyses (N = 18,637 participants amongst whom there were 4,610 cases. CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass whereas genotype (rs1130864 was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95%CI: 1.06, 1.21, and after further adjustment for confounding factors it was 1.07 (95%CI: 1.02, 1.13. Genotype (rs1130864 was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95%CI: 1.15, 1.28 and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95%CI: 1.11, 1.18, with no strong evidence in either analyses of between study heterogeneity (I(2 = 0%, p>0.9 for both analyses. There was no association of genotype (rs1130864 with CHD: pooled odds ratio 1.01 (95%CI: 0.88, 1.16 comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95%CI: 0.90, 1.03 per additional T allele (I(20.6 for both meta-analyses. An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95%CI: 0.61, 1.80. CONCLUSIONS

  10. Comparison study of inelastic analyses for high temperature structure subjected to cyclic creep loading

    International Nuclear Information System (INIS)

    Kim, J. B.; Lee, H. Y.; Lee, J. H.

    2002-01-01

    It is necessary to develop a reliable numerical analysis method to simulate the plasticity and creep behavior of LMR high temperature structures. Since general purpose finite element analysis codes such as ABAQUS and ANSYS provide various models for plastic hardening and creep equation of Norton's power law, it is possible to perform the separate iscoplasticity analysis. In this study, the high temperature structural analysis program(NONSTA-VP) implementing Chaboche's unified visco plasticity equation into ABAQUS has been developed and the viscoplastic response of the 316 SS plate having a circular hole subjected to a cyclic creep loading has been analyzed. The results among the separate visco plasticity analyses and the unified visco plasticity analysis using NONSTA-VP have been compared and the results from NONSTA-VP shows remarkable responses of stress relaxation and creep behavior during hold time compared to those from separate visco plasticity analyses. Also, it is anticipated to reduce the conservatism arising from using elastic approach for creep-fatigue damage analysis since the stress range and the strain range from the unified visco plasticity analysis has been greatly reduced compared to those from separate visco plasticity analyses and elastic analysis

  11. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  12. Association of physical activity with muscular strength and fat-free mass in adolescents: the HELENA study.

    Science.gov (United States)

    Moliner-Urdiales, Diego; Ortega, Francisco B; Vicente-Rodriguez, Germán; Rey-Lopez, Juan P; Gracia-Marco, Luis; Widhalm, Kurt; Sjöström, Michael; Moreno, Luis A; Castillo, Manuel J; Ruiz, Jonatan R

    2010-08-01

    The objective of this study is to analyse the association of objectively assessed physical activity (PA) with muscular strength and fat-free mass in adolescents, and to determine whether meeting the current PA recommendations is associated with higher levels of muscular strength and fat-free mass. The present cross-sectional study comprised 363 Spanish adolescents (180 females) aged 12.5-17.5 years. PA was assessed by accelerometry and expressed as average PA (counts/min), and min/day of inactive, light, moderate, vigorous and moderate to vigorous PA (MVPA). MVPA was dichotomized into or = 60. Upper body muscular strength was measured with the handgrip strength test, and lower body muscular strength was measured with the standing broad jump, squat jump, counter movement jump and Abalakov tests. Fat-free mass was measured by DXA. We observed positive associations between vigorous PA and all the lower body muscular strength tests except for the counter movement jump in males. PA was not associated with fat-free mass in both males and females. Male adolescents engaged in at least 60 min/day MVPA performed better in the standing broad jump test. In conclusion, the findings of the present study suggest that only vigorous PA is associated with muscular strength, particularly lower-body muscular strength in male adolescents.

  13. Deterministic analyses of severe accident issues

    International Nuclear Information System (INIS)

    Dua, S.S.; Moody, F.J.; Muralidharan, R.; Claassen, L.B.

    2004-01-01

    Severe accidents in light water reactors involve complex physical phenomena. In the past there has been a heavy reliance on simple assumptions regarding physical phenomena alongside of probability methods to evaluate risks associated with severe accidents. Recently GE has developed realistic methodologies that permit deterministic evaluations of severe accident progression and of some of the associated phenomena in the case of Boiling Water Reactors (BWRs). These deterministic analyses indicate that with appropriate system modifications, and operator actions, core damage can be prevented in most cases. Furthermore, in cases where core-melt is postulated, containment failure can either be prevented or significantly delayed to allow sufficient time for recovery actions to mitigate severe accidents

  14. Mendelian randomisation study of the associations of vitamin B12 and folate genetic risk scores with blood pressure and fasting serum lipid levels in three Danish population-based studies

    DEFF Research Database (Denmark)

    Husemoen, L L N; Skaaby, T; Thuesen, B H

    2016-01-01

    BACKGROUND/OBJECTIVES: The aim was to examine the association of genetic risk scores (GRSs) of vitamin B12 and folate-associated variants with blood pressure and lipids. SUBJECTS/METHODS: The study included 12 532 adults from three population-based studies (Inter99, Health2006 and Dan-MONICA10) c...... association between folate and HDL cholesterol exists.European Journal of Clinical Nutrition advance online publication, 24 February 2016; doi:10.1038/ejcn.2016.5....... and lipid-related outcomes in the combined analyses. Increasing number of folate increasing alleles was associated with increased high-density lipoprotein (HDL) cholesterol concentrations (β coefficient (95% CI, P-value) for regression of log-transformed HDL on the weighted GRSs, 0.081 (0.015, 0.148), P=0...

  15. Spent fuel shipping costs for transportation logistics analyses

    International Nuclear Information System (INIS)

    Cole, B.M.; Cross, R.E.; Cashwell, J.W.

    1983-05-01

    Logistics analyses supplied to the nuclear waste management programs of the U.S. Department of Energy through the Transportation Technology Center (TTC) at Sandia National Laboratories are used to predict nuclear waste material logistics, transportation packaging demands, shipping and receiving rates and transportation-related costs for alternative strategies. This study is an in-depth analysis of the problems and contingencies associated with the costs of shipping irradiated reactor fuel. These costs are extremely variable however, and have changed frequently (sometimes monthly) during the past few years due to changes in capital, fuel, and labor costs. All costs and charges reported in this study are based on January 1982 data using existing transport cask systems and should be used as relative indices only. Actual shipping costs would be negotiable for each origin-destination combination

  16. The type 2 diabetes risk allele of TMEM154-rs6813195 associates with decreased beta cell function in a study of 6,486 Danes.

    Directory of Open Access Journals (Sweden)

    Marie Neergaard Harder

    Full Text Available A trans-ethnic meta-analysis of type 2 diabetes genome-wide association studies has identified seven novel susceptibility variants in or near TMEM154, SSR1/RREB1, FAF1, POU5F1/TCF19, LPP, ARL15 and ABCB9/MPHOSPH9. The aim of our study was to investigate associations between these novel risk variants and type 2 diabetes and pre-diabetic traits in a Danish population-based study with measurements of plasma glucose and serum insulin after an oral glucose tolerance test in order to elaborate on the physiological impact of the variants.Case-control analyses were performed in up to 5,777 patients with type 2 diabetes and 7,956 individuals with normal fasting glucose levels. Quantitative trait analyses were performed in up to 5,744 Inter99 participants naïve to glucose-lowering medication. Significant associations between TMEM154-rs6813195 and the beta cell measures insulinogenic index and disposition index and between FAF1-rs17106184 and 2-hour serum insulin levels were selected for further investigation in additional Danish studies and results were combined in meta-analyses including up to 6,486 Danes.We confirmed associations with type 2 diabetes for five of the seven SNPs (TMEM154-rs6813195, FAF1-rs17106184, POU5F1/TCF19-rs3130501, ARL15-rs702634 and ABCB9/MPHOSPH9-rs4275659. The type 2 diabetes risk C-allele of TMEM154-rs6813195 associated with decreased disposition index (n=5,181, β=-0.042, p=0.012 and insulinogenic index (n=5,181, β=-0.032, p=0.043 in Inter99 and these associations remained significant in meta-analyses including four additional Danish studies (disposition index n=6,486, β=-0.042, p=0.0044; and insulinogenic index n=6,486, β=-0.037, p=0.0094. The type 2 diabetes risk G-allele of FAF1-rs17106184 associated with increased levels of 2-hour serum insulin (n=5,547, β=0.055, p=0.017 in Inter99 and also when combining effects with three additional Danish studies (n=6,260, β=0.062, p=0.0040.Studies of type 2 diabetes intermediary

  17. Epidemiological studies of radiation risks (NRPB Association)

    International Nuclear Information System (INIS)

    Muirhead, C.R.; Kellerer, A.M.; Chmelevsky, D.

    1993-01-01

    Objectives of project are: to analyse data on populations exposed to high doses of radiation, such as the Japanese atomic bomb survivors and groups of uranium miners; to examine data on populations exposed at low doses and methods for analysing such data; to perform preparatory work for the compilation of 'probability of causation' tables that are specific to EC countries and that also cover radon daughter exposures; to study the incidence and mortality from thyroid cancer in a cohort with medical exposures to 131 I; to study cancer incidence and mortality among Swedish patients given radiotherapy for skin haemangioma in childhood; and to examine the incidence of second tumours among Italian patients given radiotherapy for cancer of the head, neck, breast, endometrium, uterine cervix or thyroid. Results of the six contributions for the reporting period are presented. (R.P.) 4 refs

  18. Associations between Grawe's general mechanisms of change and Young's early maladaptive schemas in psychotherapy research: a comparative study of change processes.

    Science.gov (United States)

    Mander, Johannes V; Jacob, Gitta A; Götz, Lea; Sammet, Isa; Zipfel, Stephan; Teufel, Martin

    2015-01-01

    The study aimed at analyzing associations between Grawe's general mechanisms of change and Young's early maladaptive schemas (EMS). Therefore, 98 patients completed the Scale for the Multiperspective Assessment of General Change Mechanisms in Psychotherapy (SACiP), the Young Shema Questionnaire-Short Form Revised (YSQ S3R), and diverse outcome measures at the beginning and end of treatment. Our results are important for clinical applications, as we demonstrated strong predictive effects of change mechanisms on schema domains using regression analyses and cross-lagged panel models. Resource activation experiences seem to be especially crucial in fostering alterations in EMS, as this change mechanism demonstrated significant associations with several schema domains. Future research should investigate these aspects in more detail using observer-based micro-process analyses.

  19. Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.

    Science.gov (United States)

    Austin, Peter C; Mamdani, Muhammad M; Juurlink, David N; Hux, Janet E

    2006-09-01

    To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.

  20. Time-trend analyses of bleeding and mortality after primary percutaneous coronary intervention during out of working hours versus in-working hours: an observational study of 11 466 patients.

    Science.gov (United States)

    Iqbal, M Bilal; Khamis, Ramzi; Ilsley, Charles; Mikhail, Ghada; Crake, Tom; Firoozi, Sam; Kalra, Sundeep; Knight, Charles; Archbold, Andrew; Lim, Pitt; Mathur, Anthony; Meier, Pascal; Rakhit, Roby D; Redwood, Simon; Whitbread, Mark; Bromage, Dan; Rathod, Krishna; Jones, Daniel A; Wragg, Andrew; Dalby, Miles; MacCarthy, Phil; Malik, Iqbal S

    2015-06-01

    Primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment-elevation myocardial infarction. Resources are limited during out of working hours (OWH). Whether PPCI outside working hours is associated with worse outcomes and whether outcomes have improved over time are unknown. We analyzed 11 466 patients undergoing PPCI between 2004 and 2011 at all 8 tertiary cardiac centers in London, United Kingdom. We defined working hours as 9 am to 5 pm (Monday to Friday). We analyzed in-hospital bleeding and all-cause mortality ≤3 years, comparing OWH versus in-working hours. A total of 7494 patients (65.3%) were treated during OWH. Multivariable analyses demonstrated that PPCI during OWH was not a predictor for bleeding (odds ratio, 1.47; 95% confidence interval [CI], 0.97-2.24; P=0.071) or 3-year mortality (hazard ratio, 1.11; 95% CI, 0.94-1.32; P=0.20). This was confirmed in propensity-matched analyses. Time-stratified analyses demonstrated that PPCI during OWH was a predictor for bleeding (odds ratio, 2.00; 95% CI, 1.06-3.80; P=0.034) and 3-year mortality during 2005 to 2008 (hazard ratio, 1.23; 95% CI, 1.00-1.50; P=0.050), but this association was lost during 2009 to 2011. During 2005 to 2008, transradial access was predominantly used during in-working hours and PPCI during OWH was predictive of reduced transradial access use (odds ratio, 0.83; 95% CI, 0.71-0.98; P=0.033), but this association was lost during 2009 to 2011. In this study of unselected patients with ST-segment-elevation myocardial infarction, PPCI during OWH versus in-working hours had comparable bleeding and mortality. Time-stratified analyses demonstrated a reduction in adjusted bleeding and mortality during OWH over time. This may reflect the improved service provision, but the increased adoption of transradial access during OWH may also be contributory. © 2015 American Heart Association, Inc.

  1. Genome-wide and gene-based association studies of anxiety disorders in European and African American samples.

    Directory of Open Access Journals (Sweden)

    Takeshi Otowa

    Full Text Available Anxiety disorders (ADs are common mental disorders caused by a combination of genetic and environmental factors. Since ADs are highly comorbid with each other, partially due to shared genetic basis, studying AD phenotypes in a coordinated manner may be a powerful strategy for identifying potential genetic loci for ADs. To detect these loci, we performed genome-wide association studies (GWAS of ADs. In addition, as a complementary approach to single-locus analysis, we also conducted gene- and pathway-based analyses. GWAS data were derived from the control sample of the Molecular Genetics of Schizophrenia (MGS project (2,540 European American and 849 African American subjects genotyped on the Affymetrix GeneChip 6.0 array. We applied two phenotypic approaches: (1 categorical case-control comparisons (CC based upon psychiatric diagnoses, and (2 quantitative phenotypic factor scores (FS derived from a multivariate analysis combining information across the clinical phenotypes. Linear and logistic models were used to analyse the association with ADs using FS and CC traits, respectively. At the single locus level, no genome-wide significant association was found. A trans-population gene-based meta-analysis across both ethnic subsamples using FS identified three genes (MFAP3L on 4q32.3, NDUFAB1 and PALB2 on 16p12 with genome-wide significance (false discovery rate (FDR] <5%. At the pathway level, several terms such as transcription regulation, cytokine binding, and developmental process were significantly enriched in ADs (FDR <5%. Our approaches studying ADs as quantitative traits and utilizing the full GWAS data may be useful in identifying susceptibility genes and pathways for ADs.

  2. Association of Protein Intake with Bone Mineral Density and Bone Mineral Content among Elderly Women: The OSTPRE Fracture Prevention Study.

    Science.gov (United States)

    Isanejad, M; Sirola, J; Mursu, J; Kröger, H; Tuppurainen, M; Erkkilä, A T

    2017-01-01

    It has been hypothesized that high protein intakes are associated with lower bone mineral content (BMC). Previous studies yield conflicting results and thus far no studies have undertaken the interaction of body mass index (BMI) and physical activity with protein intakes in relation to BMC and bone mineral density (BMD). To evaluate the associations of dietary total protein (TP), animal protein (AP) and plant protein (PP) intakes with BMC and BMD and their changes. We tested also the interactions of protein intake with, obesity (BMI ≤30 vs. >30 kg/m2) and physical activity level (passive vs. active). Design/ Setting: Prospective cohort study (Osteoporosis Risk-Factor and Fracture-Prevention Study). Participants/measures: At the baseline, 554 women aged 65-72 years filled out a 3-day food record and a questionnaire covering data on lifestyle, physical activity, diseases, and medications. Intervention group received calcium 1000 mg/d and cholecalciferol 800 IU for 3 years. Control group received neither supplementation nor placebo. Bone density was measured at baseline and year 3, using dual energy x-ray absorptiometry. Multivariable regression analyses were conducted to examine the associations between protein intake and BMD and BMC. In cross-sectional analyses energy-adjusted TP (P≤0·029) and AP (P≤0·045) but not PP (g/d) were negatively associated with femoral neck (FN) BMD and BMC. Women with TP≥1·2 g/kg/body weight (BW) (Ptrend≤0·009) had lower FN, lumbar spine (LS) and total BMD and BMC. In follow-up analysis, TP (g/kg/BW) was inversely associated with LS BMD and LS BMC. The detrimental associations were stronger in women with BMI30 kg/m2 and physical activity.

  3. Human CLOCK gene-associated attention deficit hyperactivity disorder-related features in healthy adults: quantitative association study using Wender Utah Rating Scale.

    Science.gov (United States)

    Jeong, Seong Hoon; Yu, Je-Chun; Lee, Chang Hwa; Choi, Kyeong-Sook; Choi, Jung-Eun; Kim, Se Hyun; Joo, Eun-Jeong

    2014-02-01

    Circadian rhythm disturbance is highly prevalent in attention deficit hyperactivity disorder (ADHD). Recently, the association between the CLOCK gene and ADHD has been demonstrated in clinical samples, and the CLOCK gene's role was thought to be mediated by rhythm dysregulation. Meanwhile, ADHD has been suggested as the extreme end of a continuously distributed trait that can be found in the general population. Therefore, we examined two possibilities: (1) an ADHD-related continuous trait may be associated with the CLOCK gene, and (2) this association may be mediated by the degree of individuals' evening preference. To explore these possibilities, we performed a quantitative trait locus association study with a sample of 1,289 healthy adults. The Wender Utah Rating Scale (WURS) and the Composite Scale of Morningness (CSM) were utilized to measure the quantitative traits. Quantitative association analysis was performed using PLINK software. We found that rs1801260 (=T3111C) was associated with WURS scores in both allele-wise (p = 0.018) and haplotype-wise analyses (range of p values: 0.0155-0.0171) in male participants only. After controlling for the CSM total score as a covariate, the strength of the association did not change at all, suggesting that the association was not mediated by evening preference. Despite the very weak association signal, our results provide evidence that the CLOCK gene's association with ADHD in clinical samples may be generalizable to traits measured in the normal population. However, as our results failed to show a mediating role of evening preference, ongoing efforts are needed to identify the mechanisms by which the CLOCK gene determines ADHD-related traits.

  4. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases.Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits.The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  5. Patent foramen ovale, ischemic stroke and migraine: systematic review and stratified meta-analysis of association studies.

    Science.gov (United States)

    Davis, Daniel; Gregson, John; Willeit, Peter; Stephan, Blossom; Al-Shahi Salman, Rustam; Brayne, Carol

    2013-01-01

    Observational data have reported associations between patent foramen ovale (PFO), cryptogenic stroke and migraine. However, randomized trials of PFO closure do not demonstrate a clear benefit either because the underlying association is weaker than previously suggested or because the trials were underpowered. In order to resolve the apparent discrepancy between observational data and randomized trials, we investigated associations between (1) migraine and ischemic stroke, (2) PFO and ischemic stroke, and (3) PFO and migraine. Eligibility criteria were consistent; including all studies with specifically defined exposures and outcomes unrestricted by language. We focused on studies at lowest risk of bias by stratifying analyses based on methodological design and quantified associations using fixed-effects meta-analysis models. We included 37 studies of 7,686 identified. Compared to reports in the literature as a whole, studies with population-based comparators showed weaker associations between migraine with aura and cryptogenic ischemic stroke in younger women (OR 1.4; 95% CI 0.9-2.0; 1 study), PFO and ischemic stroke (HR 1.6; 95 CI 1.0-2.5; 2 studies; OR 1.3; 95% CI 0.9-1.9; 3 studies), or PFO and migraine (OR 1.0; 95% CI 0.6-1.6; 1 study). It was not possible to look for interactions or effect modifiers. These results are limited by sources of bias within individual studies. The overall pairwise associations between PFO, cryptogenic ischemic stroke and migraine do not strongly suggest a causal role for PFO. Ongoing randomized trials of PFO closure may need larger numbers of participants to detect an overall beneficial effect. Copyright © 2012 S. Karger AG, Basel.

  6. Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

    Science.gov (United States)

    Gidal, Barry E; Wechsler, Robert T; Sankar, Raman; Montouris, Georgia D; White, H Steve; Cloyd, James C; Kane, Mary Clare; Peng, Guangbin; Tworek, David M; Shen, Vivienne; Isojarvi, Jouko

    2016-10-25

    To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg -1 ·d -1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg -1 ·d -1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. NCT00518713 and NCT01160770. This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. © 2016 American Academy of Neurology.

  7. The Associations between Perceived Parenting Styles, Empathy, and Altruistic Choices in Economic Games: A Study of Chinese Children

    Directory of Open Access Journals (Sweden)

    Qingke Guo

    2017-10-01

    Full Text Available Parenting styles are critical for fostering children’s empathy and prosociality. Yet these relations haven’t been well established for Chinese children, and the underlying mechanisms were seldom explored. Drawing upon parental acceptance-rejection theory and empathy-altruism hypothesis, the objective of this study was to investigate the relationships between perceived parenting styles and altruistic behavior of children, and the intervening role of children’s empathy and the moderating role of in-group and out-group conditions. What is novel about this study is that it contains both survey data and experimental data. Four hundred and ninety-four children (Mage = 8.92 years completed four simple binary-choice dictator games which are widely used in the study of other-regarding preferences (concerns for the interests of others. These children also reported their perceived parenting styles. And children’s empathy was reported by their mothers. Each child’s altruism score, which was used in the subsequent analyses, was derived from the altruistic choices in these games. Mediation analyses indicated that, when age and gender were controlled for, maternal and paternal emotional warmth were positively associated with children’s altruism via children’s empathy, while maternal and paternal rejection were negatively associated with children’s altruism via children’s empathy. Multi-group analyses showed that the influences of perceived parenting styles on children’s altruistic behavior via children’s empathy were consistent for in-group and out-group conditions. These findings suggest that enhancing parental emotional warmth and reducing parental rejection may foster children’s empathy, which in turn promote children’s altruism. Limitations and future directions of this study were also discussed.

  8. Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach.

    Science.gov (United States)

    Spencer, Amy V; Cox, Angela; Lin, Wei-Yu; Easton, Douglas F; Michailidou, Kyriaki; Walters, Kevin

    2016-04-01

    There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples. © 2016 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.

  9. Gastric inhibitory polypeptide receptor: association analyses for obesity of several polymorphisms in large study groups

    Directory of Open Access Journals (Sweden)

    Rief Winfried

    2009-03-01

    Full Text Available Abstract Background Gastric inhibitory polypeptide (GIP is postulated to be involved in type 2 diabetes mellitus and obesity. It exerts its function through its receptor, GIPR. We genotyped three GIPR SNPs (rs8111428, rs2302382 and rs1800437 in German families with at least one obese index patient, two case-control studies and two cross-sectional population-based studies. Methods Genotyping was performed by MALDI-TOF, ARMS-PCR and RFLP. The family-study: 761 German families with at least one extremely obese child or adolescent (n = 1,041 and both parents (n = 1,522. Case-control study: (a German obese children (n = 333 and (b obese adults (n = 987 in comparison to 588 adult lean controls. The two cross-sectional population-based studies: KORA (n = 8,269 and SHIP (n = 4,310. Results We detected over-transmission of the A-allele of rs2302382 in the German families (pTDT-Test = 0.0089. In the combined case-control sample, we estimated an odd ratio of 1.54 (95%CI 1.09;2.19, pCA-Test = 0.014 for homozygotes of the rs2302382 A-allele compared to individuals with no A-allele. A similar trend was found in KORA where the rs2302382 A-allele led to an increase of 0.12 BMI units (p = 0.136. In SHIP, however, the A-allele of rs2302382 was estimated to contribute an average decrease of 0.27 BMI units (p-value = 0.031. Conclusion Our data suggest a potential relevance of GIPR variants for obesity. However, additional studies are warranted in light of the conflicting results obtained in one of the two population-based studies.

  10. Genome-Wide Association Study of Psychosis Proneness in the Finnish Population.

    Science.gov (United States)

    Ortega-Alonso, Alfredo; Ekelund, Jesper; Sarin, Antti-Pekka; Miettunen, Jouko; Veijola, Juha; Järvelin, Marjo-Riitta; Hennah, William

    2017-10-21

    The current study examined quantitative measures of psychosis proneness in a nonpsychotic population, in order to elucidate their underlying genetic architecture and to observe if there is any commonality to that already detected in the studies of individuals with overt psychotic conditions, such as schizophrenia and bipolar disorder. Heritability, univariate and multivariate genome-wide association (GWAs) tests, including a series of comprehensive gene-based association analyses, were developed in 4269 nonpsychotic persons participating in the Northern Finland Birth Cohort 1966 study with information on the following psychometric measures: Hypomanic Personality, Perceptual Aberration, Physical and Social Anhedonia (also known as Chapman's Schizotypia scales), and Schizoidia scale. Genome-wide genetic data was available for ~9.84 million SNPs. Heritability estimates ranged from 16% to 27%. Phenotypic, genetic and environmental correlations ranged from 0.04-0.43, 0.25-0.73, and 0.12-0.43, respectively. Univariate GWAs tests revealed an intronic SNP (rs12449097) at the TMC7 gene (16p12.3) that significantly associated (P = 3.485 × 10-8) with the hypomanic scale. Bivariate GWAs tests including the hypomanic and physical anhedonia scales suggested a further borderline significant SNP (rs188320715; P-value = 5.261 × 10-8, ~572 kb downstream the ARID1B gene at 6q25.3). Gene-based tests highlighted 20 additional genes of which 5 had previously been associated to schizophrenia and/or bipolar disorder: CSMD1, CCDC141, SLC1A2, CACNA1C, and SNAP25. Altogether the findings explained from 3.7% to 14.1% of the corresponding trait heritability. In conclusion, this study provides preliminary genomic evidence suggesting that qualitatively similar biological factors may underlie different psychosis proneness measures, some of which could further predispose to schizophrenia and bipolar disorder. © The Author 2017. Published by Oxford University Press on behalf of the Maryland

  11. Associations between outdoor temperature and markers of inflammation: a cohort study

    Directory of Open Access Journals (Sweden)

    Zanobetti Antonella

    2010-07-01

    Full Text Available Abstract Background Associations between ambient temperature and cardiovascular mortality are well established. This study investigated whether inflammation could be part of the mechanism leading to temperature-related cardiovascular deaths. Methods The study population consisted of a cohort of 673 men with mean age of 74.6 years, living in the greater Boston area. They were seen for examination roughly every 4 years, and blood samples for inflammation marker analyses were drawn in 2000-2008 (total of 1254 visits. We used a mixed effects model to estimate the associations between ambient temperature and a variety of inflammation markers (C-reactive protein, white blood cell count, soluble Vascular Cell Adhesion Molecule-1, soluble Intercellular Adhesion Molecule-1, tumor necrosis factor alpha, and interleukins -1β, -6 and -8. Random intercept for each subject and several possible confounders, including combustion-related air pollution and ozone, were used in the models. Results We found a 0 to 1 day lagged and up to 4 weeks cumulative responses in C-reactive protein in association with temperature. We observed a 24.9% increase [95% Confidence interval (CI: 7.36, 45.2] in C-reactive protein for a 5°C decrease in the 4 weeks' moving average of temperature. We observed similar associations also between temperature and soluble Intercellular Adhesion Molecule-1 (4.52%, 95% CI: 1.05, 8.10, over 4 weeks' moving average, and between temperature and soluble Vascular Cell Adhesion Molecule-1 (6.60%, 95% CI: 1.31, 12.2 over 4 weeks' moving average. Penalized spline models showed no deviation from linearity. There were no associations between temperature and other inflammation markers. Conclusions Cumulative exposure to decreased temperature is associated with an increase in inflammation marker levels among elderly men. This suggests that inflammation markers are part of intermediate processes, which may lead to cold-, but not heat-, related

  12. A practical introduction to Random Forest for genetic association studies in ecology and evolution.

    Science.gov (United States)

    Brieuc, Marine S O; Waters, Charles D; Drinan, Daniel P; Naish, Kerry A

    2018-03-05

    Large genomic studies are becoming increasingly common with advances in sequencing technology, and our ability to understand how genomic variation influences phenotypic variation between individuals has never been greater. The exploration of such relationships first requires the identification of associations between molecular markers and phenotypes. Here, we explore the use of Random Forest (RF), a powerful machine-learning algorithm, in genomic studies to discern loci underlying both discrete and quantitative traits, particularly when studying wild or nonmodel organisms. RF is becoming increasingly used in ecological and population genetics because, unlike traditional methods, it can efficiently analyse thousands of loci simultaneously and account for nonadditive interactions. However, understanding both the power and limitations of Random Forest is important for its proper implementation and the interpretation of results. We therefore provide a practical introduction to the algorithm and its use for identifying associations between molecular markers and phenotypes, discussing such topics as data limitations, algorithm initiation and optimization, as well as interpretation. We also provide short R tutorials as examples, with the aim of providing a guide to the implementation of the algorithm. Topics discussed here are intended to serve as an entry point for molecular ecologists interested in employing Random Forest to identify trait associations in genomic data sets. © 2018 John Wiley & Sons Ltd.

  13. Paranoid Personality Has a Dimensional Latent Structure: Taxometric Analyses of Community and Clinical Samples

    OpenAIRE

    Edens, John F.; Marcus, David K.; Morey, Leslie C.

    2009-01-01

    Although paranoid personality is one of the most commonly diagnosed personality disorders and is associated with numerous negative life consequences, relatively little is known about the structural properties of this condition. This study examines whether paranoid personality traits represent a latent dimension or a discrete class (i.e., taxon). In study 1, we conducted taxometric analyses of paranoid personality disorder criteria in a sample of 731 patients participating in the Collaborative...

  14. The association of suicide-related Twitter use with suicidal behaviour: a cross-sectional study of young internet users in Japan.

    Science.gov (United States)

    Sueki, Hajime

    2015-01-01

    Infodemiology studies for suicide prevention have become increasingly common in recent years. However, the association between Twitter use and suicide has only been partially clarified. This study examined the association between suicide-related tweets and suicidal behaviour to identify suicidal young people on the Internet. A cross-sectional survey was conducted using Internet survey panels (n=220,848) comprising users in their 20s, through a major Japanese Internet survey company. Final analyses included the data of 1000 participants. Of the participants (n=1000) used in the final analysis, 61.3% were women and the mean age was 24.9 years (SD=2.9, range=20-29). Logistic regression analyses showed that tweeting "want to die" and "want to commit suicide" was significantly related to suicidal ideation and behaviour. Lifetime suicide attempts, the most powerful predictor of future suicide out of all suicidal behaviours, were more strongly associated with tweeting "want to commit suicide" than tweeting "want to die". Having a Twitter account and tweeting daily were not associated with suicidal behaviour. An online panel survey has some inherent biases, such as coverage bias. Respondents were already registered as members of a particular Internet survey company in Japan, which limits the possibility of generalization. Twitter logs may be used to identify suicidal young Internet users. This study provides a basis for the early identification of individuals at high risk for suicide. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Genome-wide association study identified CNP12587 region underlying height variation in Chinese females.

    Directory of Open Access Journals (Sweden)

    Yin-Ping Zhang

    Full Text Available Human height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs in Chinese.Genome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs. We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.We detected 10 significant association signals for height (p<0.05 in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41 × 10(-4 was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048. Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L, was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.Our findings suggest the important genetic variants underlying height variation in Chinese.

  16. Cross-Sectional Study on the Prevalence of Intestinal Parasites and Associated Risk Factors in Teda Health Centre, Northwest Ethiopia

    OpenAIRE

    Abate, Abraraw; Kibret, Biniam; Bekalu, Eylachew; Abera, Sendeku; Teklu, Takele; Yalew, Aregawi; Endris, Mengistu; Worku, Ligabaw; Tekeste, Zinaye

    2013-01-01

    Objective. To assess the magnitude of intestinal parasitic infection and associated risk factors in Teda Health Centre, Northwest Ethiopia. Method. A cross-sectional study was conducted in Teda Health Centre from February to April, 2011. Stool samples were collected from 410 study participants and analysed by direct wet mount and formal ether concentration techniques. Furthermore, sociodemographic data were collected by using standardized questionnaire. Result. The overall prevalence of intes...

  17. Archival analyses of eyewitness identification test outcomes: what can they tell us about eyewitness memory?

    Science.gov (United States)

    Horry, Ruth; Halford, Paul; Brewer, Neil; Milne, Rebecca; Bull, Ray

    2014-02-01

    Several archival studies of eyewitness identification have been conducted, but the results have been inconsistent and contradictory. We identify some avoidable pitfalls that have been present in previous analyses and present new data that address these pitfalls. We explored associations among various estimator variables and lineup outcomes for 833 "real life" lineups, including 588 lineups in which corroborating evidence of the suspect's guilt existed. Suspect identifications were associated with exposure duration, viewing distance, and the age of the witness. Nonidentifications were associated with the number of perpetrators. We also consider some of the inherent, unavoidable limitations with archival studies and consider what such studies can really tell researchers. We conclude that differences in sampling prohibit sensible comparisons between the results of laboratory and archival studies, and that the informational value of archival studies is actually rather limited.

  18. Associations between work stress and suicidal ideation: Individual-participant data from six cross-sectional studies.

    Science.gov (United States)

    Loerbroks, Adrian; Cho, Sung-Il; Dollard, Maureen F; Zou, Jianfang; Fischer, Joachim E; Jiang, Yueying; Angerer, Peter; Herr, Raphael M; Li, Jian

    2016-11-01

    Epidemiological evidence suggests that work stress is associated with suicidal ideation (SI). However, only few studies in this area have drawn on well-established theoretical work stress models (i.e., the job-demand-control [JDC] model, the effort-reward-imbalance [ERI] model, and the model of organizational injustice [OJ]). Utilization of such models allows though for theory-based assessments and workplace interventions. Since evidence on those models' relationship with suicide-related outcomes is currently inconclusive (with regard to JDC), markedly sparse (OJ) or lacking (ERI), we aimed to provide additional or initial evidence. We drew on original data from six cross-sectional studies, which were conducted in four countries (i.e., South Korea, China, Australia, and Germany). Work stress was measured by established questionnaires and was categorized into tertiles. In each study, SI was assessed by either one or two items taken from validated scales. Associations of work stress with SI were estimated for each study and were pooled across studies using multivariate random-effects logistic modeling. In the pooled analyses (n=12,422) all three work stress models were significantly associated with SI with odds ratios fluctuating around 2. For instance, the pooled odds ratios for highest versus lowest work stress exposure in terms of job strain, OJ, and ERI equalled 1.91 (95% confidence interval [CI]=1.52, 2.41), 1.98 (95% CI=1.48, 2.65), and 2.77 (95% CI=1.57, 4.88), respectively. Patterns of associations were largely consistent across the individual studies. Our study provides robust evidence of a positive association between work stress and SI. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Clinical Perspectives of Genetic Analyses on Dyslipidemia and Coronary Artery Disease

    Science.gov (United States)

    Kawashiri, Masa-aki; Yamagishi, Masakazu

    2017-01-01

    We have learned that low-density lipoprotein (LDL) cholesterol is the cause of atherosclerosis from various aspects, including a single case with familial hypercholesterolemia, other cases with different types of Mendelian dyslipidemias, large-scale randomized controlled trials using LDL cholesterol lowering therapies, and Mendelian randomization studies using common as well as rare variants associated with LDL cholesterol levels. There is no doubt that determinations of genotypes in lipid-associated genes have contributed not only to the genetic diagnosis for Mendelian dyslipidemias but also to the discoveries of novel therapeutic targets. Furthermore, recent studies have shown that such genetic information could provide useful clues for the risk prediction as well as risk stratification in general and in particular population. We provide the current understanding of genetic analyses relating to plasma lipids and coronary artery disease. PMID:28250266

  20. Immature granulocyte detection by the SE-9000 haematology analyser during pregnancy.

    Science.gov (United States)

    Fernández-Suárez, A; Pascual, V T; Gimenez, M T F; Hernández, J F S

    2003-12-01

    The objective of this study was to determine the nature of the alarm for immature granulocytes appearing in haemograms from pregnant women, as detected by the immature cell information channel (IMI) of the SE-9000 automated haematology analyser. Of all tests run on pregnant women in a 4-month period (n = 698), the first 100 haemograms with immature granulocyte alarms (14.33%) were collected. Each of these samples was then stained with Wright-Giemsa stain. The following variables were also analysed: age of the mother, trimester and days of gestation, type of delivery, weight and sex of the baby, and Apgar score. Most pregnant women were in the third trimester of gestation (82%) when an alarm was noted on the IMI channel. Of the patients, 62% had normal deliveries. The most frequent complication was obstructed delivery (23%). Mean percentages by microscopic counts of band cells, metamyelocytes, and myelocytes were 2.99, 0.45, and 0.19%, respectively. There was a statistically significant correlation for all cell types between the SE-9000 and the manual count method. No association was observed between the presence of immature granulocytes and the clinical variables analysed. The SE-9000 analyser shows high sensitivity in the IMI channel for detection of immature forms.

  1. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I

    2010-01-01

    in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P SH2B1 and BDNF) map near key hypothalamic regulators...

  2. Factors of U.S. Hospitals Associated with Improved Profit Margins: An Observational Study.

    Science.gov (United States)

    Ly, Dan P; Cutler, David M

    2018-02-14

    Hospitals face financial pressure from decreased margins from Medicare and Medicaid and lower reimbursement from consolidating insurers. The objectives of this study are to determine whether hospitals that became more profitable increased revenues or decreased costs more and to examine characteristics associated with improved financial performance over time. The design of this study is retrospective analyses of U.S. non-federal acute care hospitals between 2003 and 2013. There are 2824 hospitals as subjects of this study. The main measures of this study are the change in clinical operating margin, change in revenues per bed, and change in expenses per bed between 2003 and 2013. Hospitals that became more profitable had a larger magnitude of increases in revenue per bed (about $113,000 per year [95% confidence interval: $93,132 to $133,401]) than of decreases in costs per bed (about - $10,000 per year [95% confidence interval: - $28,956 to $9617]), largely driven by higher non-Medicare reimbursement. Hospitals that improved their margins were larger or joined a hospital system. Not-for-profit status was associated with increases in operating margin, while rural status and having a larger share of Medicare patients were associated with decreases in operating margin. There was no association between improved hospital profitability and changes in diagnosis related group weight, in number of profitable services, or in payer mix. Hospitals that became more profitable were more likely to increase their admissions per bed per year. Differential price increases have led to improved margins for some hospitals over time. Where significant price increases are not possible, hospitals will have to become more efficient to maintain profitability.

  3. Associations between Obesity and Spinal Diseases: A Medical Expenditure Panel Study Analysis

    Directory of Open Access Journals (Sweden)

    Binwu Sheng

    2017-02-01

    Full Text Available Background: The link between body weight status and spinal diseases has been suggested by a number of cross-sectional and cohort studies with a limited range of patient populations. No population-representative samples have been used to examine the link between obesity and spinal diseases. The present study is based on a nationally representative sample drawn from the Medical Expenditure Panel Survey. Methods: Using the cross-sectional sample of the 2014 Medical Expenditure Panel Study, we built four weighted logistic regression analyses of the associations between body weight status and the following four spinal diseases: low back pain, spondylosis, other cervical disorders and intervertebral disc disorder (IDD. Each respondent’s body weight status was used as the key independent variable with three categories: normal/underweight, overweight, and obese. We controlled for marital status, gender, age, smoking status, household income, health insurance coverage, educational attainment and the use of health services for other major categories of diseases. Results: A total sample of 23,048 respondents was used in our analysis. Overweight and obese respondents, as compared to normal/underweight respondents, were more likely to develop lower back problems (Overweight: logged odds = 0.218, p < 0.01; Obese: logged odds = 0.395, p < 0.001 and IDD (Overweight: logged odds = 0.441, p < 0.05; Obese: logged odds = 0.528, p < 0.001. The associations between bodyweight status and spondylitis were statistically insignificant (Overweight: logged odds = 0.281, p = 0.442; Obese: logged odds = 0.680, p = 0.104. The associations between body weight status and other cervical disorders (Overweight: logged odds = −0.116, p = 0.304; Obese: logged odds = −0.160, p = 0.865 were statistically insignificant. Conclusions: As the first study using a national sample to study bodyweight and spinal diseases, our paper supports the hypothesis that obesity adds to the burden

  4. CO{sub 2} Sequestration Capacity and Associated Aspects of the Most Promising Geologic Formations in the Rocky Mountain Region: Local-Scale Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Laes, Denise; Eisinger, Chris; Morgan, Craig; Rauzi, Steve; Scholle, Dana; Scott, Phyllis; Lee, Si-Yong; Zaluski, Wade; Esser, Richard; Matthews, Vince; McPherson, Brian

    2013-07-30

    The purpose of this report is to provide a summary of individual local-­scale CCS site characterization studies conducted in Colorado, New Mexico and Utah. These site-­ specific characterization analyses were performed as part of the “Characterization of Most Promising Sequestration Formations in the Rocky Mountain Region” (RMCCS) project. The primary objective of these local-­scale analyses is to provide a basis for regional-­scale characterization efforts within each state. Specifically, limits on time and funding will typically inhibit CCS projects from conducting high-­ resolution characterization of a state-­sized region, but smaller (< 10,000 km{sup 2}) site analyses are usually possible, and such can provide insight regarding limiting factors for the regional-­scale geology. For the RMCCS project, the outcomes of these local-­scale studies provide a starting point for future local-­scale site characterization efforts in the Rocky Mountain region.

  5. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    Science.gov (United States)

    Lasram, Khaled; Ben Halim, Nizar; Hsouna, Sana; Kefi, Rym; Arfa, Imen; Ghazouani, Welid; Jamoussi, Henda; Benrahma, Houda; Kharrat, Najla; Rebai, Ahmed; Ben Ammar, Slim; Bahri, Sonia; Barakat, Abdelhamid; Abid, Abdelmajid; Abdelhak, Sonia

    2014-01-01

    Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P = 0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P < 10−3 and OR = 1.33, 95% CI = 1.13–1.56, and P = 0.001, resp.). Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs. PMID:25165692

  6. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Khaled Lasram

    2014-01-01

    Full Text Available Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.. Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P=0.007. Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P<10-3 and OR = 1.33, 95% CI = 1.13–1.56, and P=0.001, resp.. Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs.

  7. XRF analyses for the study of painting technique and degradation on frescoes by Beato Angelico: first results

    International Nuclear Information System (INIS)

    Mazzinghi, A.

    2014-01-01

    Beato Angelico is one of the most important Italian painters of the Renaissance period, in particular he was a master of the so-called 'Buon fresco' technique for mural paintings. A wide diagnostic campaign with X-Ray Fluorescence (XRF) analyses has been carried out on three masterworks painted by Beato Angelico in the San Marco monastery in Florence: the Crocifissione con Santi, the 'Annunciazione' and the 'Madonna delle Ombre'. The latter is painted by mixing fresco and secco techniques, which makes it of particular interest for the study of two different paintings techniques of the same artist. Then the aim of the study was focused on the characterization of the painting palette, and therefore the painting techniques, used by Beato Angelico. Moreover, the conservators were interested in the study of degradation processes and old restoration treatments. Our analyses have been carried out by means of the XRF spectrometer developed at LABEC laboratory at Istituto Nazionale di Fisica Nucleare in Florence (Italy). XRF is indeed especially suited for such a kind of study, allowing for multi-elemental, nondestructive, non-invasive analyses in a short time, with portable instruments. In this paper the first results concerning the XRF analysis are presented.

  8. The genetic aetiology of cannabis use initiation: A meta-analysis of genome-wide association studies and a SNP-based heritability estimation

    NARCIS (Netherlands)

    Verweij, K.J.H.; Vinkhuyzen, A.A.E.; Benyamin, B.; Lynskey, M.T.; Quaye, L.; Agrawal, A.; Gordon, S.D.; Montgomery, G.W.; Madden, P.A.F.; Heath, A.C.; Spector, T.D.; Martin, N.G.; Medland, S.E.

    2013-01-01

    While initiation of cannabis use is around 40% heritable, not much is known about the underlying genetic aetiology. Here, we meta-analysed two genome-wide association studies of initiation of cannabis use with >10000 individuals. None of the genetic variants reached genome-wide significance. We also

  9. The genetic etiology of cannabis use initiation: a meta-analysis of genome-wide association studies, and a SNP-based heritability estimation.

    NARCIS (Netherlands)

    Verweij, K.J.H.; Vinkhuyzen, A.A.E.; Benyamin, B.; Lynskey, M.T.; Quaye, L.; Agrawal, A.; Gordon, S.D.; Montgomery, G.W.; Madden, P.A.F.; Heath, A.C.; Spector, T.D.; Martin, N.G.; Medland, S.E.

    2013-01-01

    While initiation of cannabis use is around 40% heritable, not much is known about the underlying genetic aetiology. Here, we meta-analysed two genome-wide association studies of initiation of cannabis use with > 10 000 individuals. None of the genetic variants reached genome-wide significance. We

  10. Cross-lagged associations between children's stress and adiposity: the Children's Body Composition and Stress study.

    Science.gov (United States)

    Michels, Nathalie; Sioen, Isabelle; Boone, Liesbet; Clays, Els; Vanaelst, Barbara; Huybrechts, Inge; De Henauw, Stefaan

    2015-01-01

    The public health threats stress and adiposity have previously been associated with each other. Longitudinal studies are needed to reveal whether this association is bidirectional and the moderating factors. In the longitudinal Children's Body Composition and Stress study, 316 children (aged 5-12 years) had measures of stress (questionnaires concerning negative life events, problem behavior, and emotions) and adiposity (body mass index, waist-to-height ratio, and fat percentage) in three waves at 1-year intervals. The bidirectionality of the association between stress and adiposity was examined using cross-lagged analyses. We tested moderation by cortisol and life-style (physical activity, screen time, food consumption, eating behavior and sleep duration). Adiposity (body mass index: β = 0.48 and fat percentage: β = 0.18; p stress levels, but stress was not directly related to subsequent increases in adiposity indices. Cortisol and life-style factors displayed a moderating effect on the association between stress and adiposity. Stress was positively associated with adiposity in children with high cortisol awakening patterns (β = 0.204; p = .020) and high sweet food consumption (β = 0.190; p = .031), whereas stress was associated with lower adiposity in the most active children (β = -0.163; p = .022). Stress is associated with the development of children's adiposity, but the effects depend on cortisol levels and life-style factors. This creates new perspectives for multifactorial obesity prevention programs. Our results also highlight the adverse effect of an unhealthy body composition on children's psychological well-being.

  11. LWR safety studies. Analyses and further assessments relating to the German Risk Assessment Study on Nuclear Power Plants. Vol. 3

    International Nuclear Information System (INIS)

    1983-01-01

    Critical review of the analyses of the German Risk Assessment Study on Nuclear Power Plants (DRS) concerning the reliability of the containment under accident conditions and the conditions of fission product release (transport and distribution in the environment). Main point of interest in this context is an explosion in the steam section and its impact on the containment. Critical comments are given on the models used in the DRS for determining the accident consequences. The analyses made deal with the mathematical models and database for propagation calculations, the methods of dose computation and assessment of health hazards, and the modelling of protective and safety measures. Social impacts of reactor accidents are also considered. (RF) [de

  12. The association of depressive symptoms and physical diseases in Switzerland: a cross-sectional general population study

    Directory of Open Access Journals (Sweden)

    Donja eRodic

    2015-03-01

    Full Text Available Objective: To estimate the association between depressive symptoms and physical diseases in Switzerland, as respective findings might inform about future estimates of mental and physical health care costs.Methods: A population-based study, using data from the Swiss Health Survey collected by computer assisted telephone interviews and additional written questionnaires during the year 2007 (n = 18,760 in Switzerland. The multistage stratified random sample included subjects aged 15 and older, living in a private Swiss household with a telephone connection. Complete data was available for 14,348 subjects (51% of all subjects reached by telephone. Logistic regression analyses were used to estimate the associations between depressive symptoms and any physical disease, or a specific physical disease out of 13 non-communicable physical diseases assessed with a self-report checklist on common physical diseases. Analyses were adjusted for sex, age, education, occupation and household income. Results: In the adjusted models depressive symptoms were associated with arthrosis and arthritis (Odds Ratio [OR] = 1.79, 95% Confidence Interval [CI] = 1.28−2.50 and any physical disease (OR = 1.67, 95% CI = 1.33−2.10 after controlling for multiple testing.Conclusion: Our findings contribute to a better understanding of the comorbidity of depressive symptoms and arthrosis and arthritis in Switzerland and might have implications for more precise future estimates of mental and physical health care costs.

  13. Serum Lipid Profiles and Cancer Risk in the Context of Obesity: Four Meta-Analyses

    International Nuclear Information System (INIS)

    Melvin, J. C.; Holmberg, L.; Hemelrijck, M. V.

    2013-01-01

    The objective here was to summarize the evidence for, and quantify the link between, serum markers of lipid metabolism and risk of obesity-related cancers. Pub Med and Embase were searched using predefined inclusion criteria to conduct meta-analyses on the association between serum levels of TG, TC, HDL, ApoA-I, and risk of 11 obesity-related cancers. Pooled relative risks (RRs) and 95% confidence intervals were estimated using random-effects analyses. 28 studies were included. Associations between abnormal lipid components and risk of obesity-related cancers when using clinical cut points ( TC ≥ 6.50; TG ≥ 1.71; HDL ≤ 1.03; ApoA-I ≤ 1.05 mmol/L) were apparent in all models. RRs were 1.18 (95% CI: 1.08-1.29) for TC, 1.20 (1.07-1.35) for TG, 1.15 (1.01-1.32) for HDL, and 1.42 (1.17-1.74) for ApoA-I. High levels of TC and TG, as well as low levels of HDL and ApoA-I, were consistently associated with increased risk of obesity-related cancers. The modest RRs suggest serum lipids to be associated with the risk of cancer, but indicate it is likely that other markers of the metabolism and/or lifestyle factors may also be involved. Future intervention studies involving lifestyle modification would provide insight into the potential biological role of lipid metabolism in tumorigenesis.

  14. Overweight and obesity are progressively associated with lower work ability in the general working population: cross-sectional study among 10,000 adults.

    Science.gov (United States)

    Andersen, Lars L; Izquierdo, Mikel; Sundstrup, Emil

    2017-11-01

    Obesity is associated with many diseases and functional limitations. Workplaces are not always designed to accommodate this challenge. This study investigated the association between body mass index (BMI) and work ability in the general working population. Currently employed wage earners (N = 10,427) from the 2010 round of the Danish Work Environment Cohort Study (DWECS) replied to questions about work and health. Cumulative logistic regression analyses controlling for age, gender, physical and psychosocial work factors, lifestyle, and chronic diseases modeled the associations between BMI and work ability. BMIs above the normal range were progressively associated with lower work ability in relation to the physical demands of the job. Odds ratios for having lower work ability were 1.11 (95% CI 1.01-1.22), 1.17 (95% CI 1.01-1.34), 1.43 (95% CI 1.09-1.88), 1.69 (95% CI 1.10-2.62) for overweight and obesity classes I, II, and III, respectively. In subgroup analyses, the associations between BMI and work ability were more pronounced among individuals with mainly sedentary work than among those with physically active work. BMI was not associated with work ability in relation to the mental demands of the work. BMIs above the normal range are progressively associated with lower work ability in relation to the physical demands of the job, especially among individuals with mainly sedentary work. Ergonomic research on how to optimally design workstations for workers with obesity are needed.

  15. Association of UV radiation with Parkinson disease incidence: A nationwide French ecologic study

    International Nuclear Information System (INIS)

    Kravietz, Adam; Kab, Sofiane; Wald, Lucien; Dugravot, Aline; Singh-Manoux, Archana; Moisan, Frédéric; Elbaz, Alexis

    2017-01-01

    Background: Vitamin D is thought to contribute to brain health, but it is unclear whether low vitamin D levels are associated with increased incidence of Parkinson's disease (PD). Using ultraviolet B (UV-B) as a surrogate for vitamin D levels, we conducted a nationwide ecologic study in France in order to examine the association of UV-B with PD incidence. Methods: We used French national drug claims databases to identify PD cases using a validated algorithm. UV-B data from the solar radiation database were derived from satellite images. We estimated PD incidence (2010–2012) at the canton level (small administrative French unit) and used multilevel Poisson regression to examine its association with UV-B (2005 annual average), after adjustment for age, sex, deprivation index, density of neurologists, smoking, proportion of agricultural land, and vitamin D supplementation. Results: Analyses are based on 69,010 incident PD patients. The association between UV-B and PD incidence was quadratic (P<0.001) and modified by age (P<0.001). Below 70y, incidence was higher in the bottom quintile (relative risk, RR Q1:45-49y =1.18, 95% CI=1.08–1.29) compared with the middle UV-B quintile, and lower in the top quintile (RR Q5:45-49y =0.85 [0.77–0.94]). An opposite pattern was observed in older subjects (RR Q1:85-89y =0.92 [0.89–0.96]; RR Q5:85-89y =1.06 [1.02–1.11]). Analysis based on continuous UV-B yielded similar conclusions. Conclusions: In this nationwide study, there was an age-dependent quadratic association between UV-B and PD incidence. This study suggests that reasonable UV-B exposure is associated with lower PD risk in younger persons and that future studies should examine dose-response relations and take age into account. - Highlights: • There is an age-dependent quadratic association between UV-B and PD incidence. • Reasonable UV-B exposure is beneficial in younger persons for the risk of PD. • Our findings are consistent with a role of vitamin D

  16. Association between periodontal disease and mortality in people with CKD: a meta-analysis of cohort studies.

    Science.gov (United States)

    Zhang, Jian; Jiang, Hong; Sun, Min; Chen, Jianghua

    2017-08-16

    Periodontal disease occurs relatively prevalently in people with chronic kidney disease (CKD), but it remains indeterminate whether periodontal disease is an independent risk factor for premature death in this population. Interventions to reduce mortality in CKD population consistently yield to unsatisfactory results and new targets are necessitated. So this meta-analysis aimed to evaluate the association between periodontal disease and mortality in the CKD population. Pubmed, Embase, Web of Science, Scopus and abstracts from recent relevant meeting were searched by two authors independently. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated for overall and subgroup meta-analyses. Statistical heterogeneity was explored by chi-square test and quantified by the I 2 statistic. Eight cohort studies comprising 5477 individuals with CKD were incorporated. The overall pooled data demonstrated that periodontal disease was associated with all-cause death in CKD population (RR, 1.254; 95% CI 1.046-1.503; P = 0.005), with a moderate heterogeneity, I 2  = 52.2%. However, no evident association was observed between periodontal disease and cardiovascular mortality (RR, 1.30, 95% CI, 0.82-2.06; P = 0.259). Besides, statistical heterogeneity was substantial (I 2  = 72.5%; P = 0.012). Associations for mortality were similar between subgroups, such as the different stages of CKD, adjustment for confounding factors. Specific to all-cause death, sensitivity and cumulative analyses both suggested that our results were robust. As for cardiovascular mortality, the association with periodontal disease needs to be further strengthened. We demonstrated that periodontal disease was associated with an increased risk of all-cause death in CKD people. Yet no adequate evidence suggested periodontal disease was also at elevated risk for cardiovascular death.

  17. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  18. BioSMACK: a linux live CD for genome-wide association analyses.

    Science.gov (United States)

    Hong, Chang Bum; Kim, Young Jin; Moon, Sanghoon; Shin, Young-Ah; Go, Min Jin; Kim, Dong-Joon; Lee, Jong-Young; Cho, Yoon Shin

    2012-01-01

    Recent advances in high-throughput genotyping technologies have enabled us to conduct a genome-wide association study (GWAS) on a large cohort. However, analyzing millions of single nucleotide polymorphisms (SNPs) is still a difficult task for researchers conducting a GWAS. Several difficulties such as compatibilities and dependencies are often encountered by researchers using analytical tools, during the installation of software. This is a huge obstacle to any research institute without computing facilities and specialists. Therefore, a proper research environment is an urgent need for researchers working on GWAS. We developed BioSMACK to provide a research environment for GWAS that requires no configuration and is easy to use. BioSMACK is based on the Ubuntu Live CD that offers a complete Linux-based operating system environment without installation. Moreover, we provide users with a GWAS manual consisting of a series of guidelines for GWAS and useful examples. BioSMACK is freely available at http://ksnp.cdc. go.kr/biosmack.

  19. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    DEFF Research Database (Denmark)

    Børglum, A D; Demontis, D; Grove, J

    2014-01-01

    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals...... born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases...... was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies....

  20. Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study

    Science.gov (United States)

    Gonzalez, Suzanne; Xu, Chun; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Salvador A; Contreras, Javier; Dassori, Albana; Leach, Robin J; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2013-01-01

    Objectives Through recent genome-wide association studies (GWAS), several groups have reported significant association between variants in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) and bipolar disorder (BP) in European and European-American cohorts. We performed a family-based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods This study consisted of 913 individuals from 215 Latino pedigrees recruited from the United States, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single-nucleotide polymorphisms (SNPs) that spanned a 602.9 kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family-Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results An eight-locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population. PMID:23437964

  1. Factors Associated with Exclusive Breastfeeding of Preterm Infants. Results from a Prospective National Cohort Study

    DEFF Research Database (Denmark)

    Maastrup, Ragnhild; Hansen, Bo Moelholm; Kronborg, Hanne

    2014-01-01

    BACKGROUND AND AIM: Evidence-based knowledge of how to guide the mothers of preterm infants in breastfeeding establishment is contradictive or sparse. The aim was to investigate the associations between pre-specified clinical practices for facilitating breastfeeding, and exclusive breastfeeding...... were analysed by multiple logistic regression analyses. RESULTS: At discharge 68% of the preterm infants were exclusively breastfed and 17% partially. Test-weighing the infant, and minimizing the use of a pacifier, showed a protective effect to exclusive breastfeeding at discharge (OR 0.6 (95% CI 0.......4-0.8) and 0.4 (95% CI 0.3-0.6), respectively). The use of nipple shields (OR 2.3 (95% CI 1.6-3.2)) and the initiation of breast milk expression later than 48 hours postpartum (OR 4.9 (95% CI 1.9-12.6)) were associated with failure of exclusive breastfeeding at discharge. The clinical practices associated...

  2. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses?

    Science.gov (United States)

    McAuley, L; Pham, B; Tugwell, P; Moher, D

    2000-10-07

    The inclusion of only a subset of all available evidence in a meta-analysis may introduce biases and threaten its validity; this is particularly likely if the subset of included studies differ from those not included, which may be the case for published and grey literature (unpublished studies, with limited distribution). We set out to examine whether exclusion of grey literature, compared with its inclusion in meta-analysis, provides different estimates of the effectiveness of interventions assessed in randomised trials. From a random sample of 135 meta-analyses, we identified and retrieved 33 publications that included both grey and published primary studies. The 33 publications contributed 41 separate meta-analyses from several disease areas. General characteristics of the meta-analyses and associated studies and outcome data at the trial level were collected. We explored the effects of the inclusion of grey literature on the quantitative results using logistic-regression analyses. 33% of the meta-analyses were found to include some form of grey literature. The grey literature, when included, accounts for between 4.5% and 75% of the studies in a meta-analysis. On average, published work, compared with grey literature, yielded significantly larger estimates of the intervention effect by 15% (ratio of odds ratios=1.15 [95% CI 1.04-1.28]). Excluding abstracts from the analysis further compounded the exaggeration (1.33 [1.10-1.60]). The exclusion of grey literature from meta-analyses can lead to exaggerated estimates of intervention effectiveness. In general, meta-analysts should attempt to identify, retrieve, and include all reports, grey and published, that meet predefined inclusion criteria.

  3. Application of RUNTA code in flood analyses

    International Nuclear Information System (INIS)

    Perez Martin, F.; Benitez Fonzalez, F.

    1994-01-01

    Flood probability analyses carried out to date indicate the need to evaluate a large number of flood scenarios. This necessity is due to a variety of reasons, the most important of which include: - Large number of potential flood sources - Wide variety of characteristics of flood sources - Large possibility of flood-affected areas becoming inter linked, depending on the location of the potential flood sources - Diversity of flood flows from one flood source, depending on the size of the rupture and mode of operation - Isolation times applicable - Uncertainties in respect of the structural resistance of doors, penetration seals and floors - Applicable degrees of obstruction of floor drainage system Consequently, a tool which carries out the large number of calculations usually required in flood analyses, with speed and flexibility, is considered necessary. The RUNTA Code enables the range of possible scenarios to be calculated numerically, in accordance with all those parameters which, as a result of previous flood analyses, it is necessary to take into account in order to cover all the possible floods associated with each flood area

  4. Genome-wide association study of handedness excludes simple genetic models

    Science.gov (United States)

    Armour, J AL; Davison, A; McManus, I C

    2014-01-01

    Handedness is a human behavioural phenotype that appears to be congenital, and is often assumed to be inherited, but for which the developmental origin and underlying causation(s) have been elusive. Models of the genetic basis of variation in handedness have been proposed that fit different features of the observed resemblance between relatives, but none has been decisively tested or a corresponding causative locus identified. In this study, we applied data from well-characterised individuals studied at the London Twin Research Unit. Analysis of genome-wide SNP data from 3940 twins failed to identify any locus associated with handedness at a genome-wide level of significance. The most straightforward interpretation of our analyses is that they exclude the simplest formulations of the ‘right-shift' model of Annett and the ‘dextral/chance' model of McManus, although more complex modifications of those models are still compatible with our observations. For polygenic effects, our study is inadequately powered to reliably detect alleles with effect sizes corresponding to an odds ratio of 1.2, but should have good power to detect effects at an odds ratio of 2 or more. PMID:24065183

  5. Combined Metabonomic and Quantitative RT-PCR Analyses Revealed Metabolic Reprogramming Associated with Fusarium graminearum Resistance in Transgenic Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Fangfang Chen

    2018-01-01

    Full Text Available Fusarium head blight disease resulting from Fusarium graminearum (FG infection causes huge losses in global production of cereals and development of FG-resistant plants is urgently needed. To understand biochemistry mechanisms for FG resistance, here, we have systematically investigated the plant metabolomic phenotypes associated with FG resistance for transgenic Arabidopsis thaliana expressing a class-I chitinase (Chi, a Fusarium-specific recombinant antibody gene (CWP2 and fused Chi-CWP2. Plant disease indices, mycotoxin levels, metabonomic characteristics, and expression levels of several key genes were measured together with their correlations. We found that A. thaliana expressing Chi-CWP2 showed higher FG resistance with much lower disease indices and mycotoxin levels than the wild-type and the plants expressing Chi or CWP2 alone. The combined metabonomic and quantitative RT-PCR analyses revealed that such FG-resistance was closely associated with the promoted biosynthesis of secondary metabolites (phenylpropanoids, alkanoids and organic osmolytes (proline, betaine, glucose, myo-inositol together with enhanced TCA cycle and GABA shunt. These suggest that the concurrently enhanced biosyntheses of the shikimate-mediated secondary metabolites and organic osmolytes be an important strategy for A. thaliana to develop and improve FG resistance. These findings provide essential biochemical information related to FG resistance which is important for developing FG-resistant cereals.

  6. The role of CFD computer analyses in hydrogen safety management

    International Nuclear Information System (INIS)

    Komen, E.M.J; Visser, D.C; Roelofs, F.; Te Lintelo, J.G.T

    2014-01-01

    The risks of hydrogen release and combustion during a severe accident in a light water reactor have attracted considerable attention after the Fukushima accident in Japan. Reliable computer analyses are needed for the optimal design of hydrogen mitigation systems, like e.g. passive autocatalytic recombiners (PARs), and for the assessment of the associated residual risk of hydrogen combustion. Traditionally, so-called Lumped Parameter (LP) computer codes are being used for these purposes. In the last decade, significant progress has been made in the development, validation, and application of more detailed, three-dimensional Computational Fluid Dynamics (CFD) simulations for hydrogen safety analyses. The objective of the current paper is to address the following questions: - When are CFD computer analyses needed complementary to the traditional LP code analyses for hydrogen safety management? - What is the validation status of the CFD computer code for hydrogen distribution, mitigation, and combustion analyses? - Can CFD computer analyses nowadays be executed in practical and reliable way for full scale containments? The validation status and reliability of CFD code simulations will be illustrated by validation analyses performed for experiments executed in the PANDA, THAI, and ENACCEF facilities. (authors)

  7. Periodontitis is associated with endothelial dysfunction in a general population: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Birte Holtfreter

    Full Text Available A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men aged 25-85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL and pocket probing depth (PPD as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005. Measurements of FMD and nitroglycerin-mediated dilation (NMD were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥ 6 mm with FMD (p(trend=0.048, with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p<0.05. Consistently, FMD values increased significantly across categories of the percentage of sites with CAL ≥ 6 mm (p(trend=0.01 and the periodontitis case definition (p(trend=0.006. Restrictions to subjects without antihypertensive or statin medication or current non-smokers confirmed previous results. Systemic inflammation did not seem to mediate the relation. Both PPD and CAL were not consistently associated with NMD. In contrast to previous studies, high levels of periodontal disease were significantly associated with high FMD values. This

  8. Socio-economic factors associated with a healthy diet: results from the E3N study.

    Science.gov (United States)

    Affret, Aurélie; Severi, Gianluca; Dow, Courtney; Rey, Grégoire; Delpierre, Cyrille; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy

    2017-06-01

    To identify individual and contextual socio-economic factors associated with a healthy diet. Dietary data from a large cohort study were used to derive two mutually exclusive dietary patterns through a latent class analysis. Associations between dietary patterns and socio-economic factors were studied with logistic regression. E3N, a French prospective cohort study composed of women recruited from a national health insurance plan covering people working in the national education system. E3N participants (n 73 031) with dietary and socio-economic data available. The 'Healthy' pattern was characterized by a large consumption of fruits and vegetables and the 'Less Healthy' pattern by a large consumption of pizza and processed meat. When all socio-economic factors were analysed together, all of the individual factors considered were associated with a healthy diet (e.g. women with three or more children were less likely to follow a healthy diet v. women with no children, OR (95 % CI): 0·70 (0·66, 0·75)) while the contextual factors associated with a healthy diet included the size of the agglomeration of residence and the area of birth and residence (e.g. women living in the West of France were less likely to follow a healthy diet v. those living in the South of France: 0·78 (0·72, 0·83)). We demonstrated that individual and contextual factors are both associated with diet. Rather than focusing only on individual factors, we recommend future studies or public health and nutritional strategies on diet to consider both types of factors.

  9. Association between intake of dairy products and short-term memory with and without adjustment for genetic and family environmental factors: A twin study.

    Science.gov (United States)

    Ogata, Soshiro; Tanaka, Haruka; Omura, Kayoko; Honda, Chika; Hayakawa, Kazuo

    2016-04-01

    Previous studies have indicated associations between intake of dairy products and better cognitive function and reduced risk of dementia. However, these studies did not adjust for genetic and family environmental factors that may influence food intake, cognitive function, and metabolism of dairy product nutrients. In the present study, we investigated the association between intake of dairy products and short-term memory with and without adjustment for almost all genetic and family environmental factors using a genetically informative sample of twin pairs. A cross-sectional study was conducted among twin pairs aged between 20 and 74. Short-term memory was assessed as primary outcome variable, intake of dairy products was analyzed as the predictive variable, and sex, age, education level, marital status, current smoking status, body mass index, dietary alcohol intake, and medical history of hypertension or diabetes were included as possible covariates. Generalized estimating equations (GEE) were performed by treating twins as individuals and regression analyses were used to identify within-pair differences of a twin pair to adjust for genetic and family environmental factors. Data are reported as standardized coefficients and 95% confidence intervals (CI). Analyses were performed on data from 78 men and 278 women. Among men, high intake of dairy products was significantly associated with better short-term memory after adjustment for the possible covariates (standardized coefficients = 0.22; 95% CI, 0.06-0.38) and almost all genetic and family environmental factors (standardized coefficients = 0.38; 95% CI, 0.07-0.69). Among women, no significant associations were found between intake of dairy products and short-term memory. Subsequent sensitivity analyses were adjusted for small samples and showed similar results. Intake of dairy product may prevent cognitive declines regardless of genetic and family environmental factors in men. Copyright © 2015 Elsevier Ltd

  10. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    A. Okbay (Aysu); Baselmans, B.M.L. (Bart M.L.); J.E. de Neve (Jan-Emmanuel); P. Turley (Patrick); M. Nivard (Michel); Fontana, M.A. (Mark Alan); Meddens, S.F.W. (S. Fleur W.); Linnér, R.K. (Richard Karlsson); Rietveld, C.A. (Cornelius A); J. Derringer; J. Gratten (Jacob); J.J. Lee (James J.); Liu, J.Z. (Jimmy Z); R. de Vlaming (Ronald); SAhluwalia, T. (Tarunveer); Buchwald, J. (Jadwiga); A. Cavadino (Alana); A.C. Frazier-Wood (Alexis C.); Furlotte, N.A. (Nicholas A); Garfield, V. (Victoria); Geisel, M.H. (Marie Henrike); J.R. Gonzalez (Juan R.); Haitjema, S. (Saskia); R. Karlsson (Robert); Der Laan, S.W. (Sander Wvan); K.-H. Ladwig (Karl-Heinz); J. Lahti (Jari); S.J. van der Lee (Sven); P.A. Lind (Penelope); Liu, T. (Tian); Matteson, L. (Lindsay); E. Mihailov (Evelin); M. Miller (Mike); CMinica, C. (Camelia); MNolte, I. (Ilja); D.O. Mook-Kanamori (Dennis); P.J. van der Most (Peter); C. Oldmeadow (Christopher); Y. Qian (Yong); O. Raitakari (Olli); R. Rawal (R.); A. Realo; Rueedi, R. (Rico); Schmidt, B. (Börge); A.V. Smith (Albert Vernon); E. Stergiakouli (Evangelia); T. Tanaka (Toshiko); K.D. Taylor (Kent); Wedenoja, J. (Juho); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); MWillems, S. (Sara); Zhao, W. (Wei); L.C. Study (LifeLines Cohort); N. Amin (Najaf); Bakshi, A. (Andrew); P.A. Boyle (Patricia); Cherney, S. (Samantha); Cox, S.R. (Simon R); G. Davies (Gail); O.S.P. Davis (Oliver S.); J. Ding (Jun); N. Direk (Nese); Eibich, P. (Peter); R. Emeny (Rebecca); Fatemifar, G. (Ghazaleh); J.D. Faul; L. Ferrucci (Luigi); A.J. Forstner (Andreas); C. Gieger (Christian); Gupta, R. (Richa); T.B. Harris (Tamara); J.M. Harris (Juliette); E.G. Holliday (Elizabeth); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); M. Kaakinen (Marika); E. Kajantie (Eero); Karhunen, V. (Ville); I. Kolcic (Ivana); M. Kumari (Meena); L.J. Launer (Lenore); L. Franke (Lude); Li-Gao, R. (Ruifang); Koini, M. (Marisa); A. Loukola (Anu); P. Marques-Vidal; G.W. Montgomery (Grant); M. Mosing (Miriam); L. Paternoster (Lavinia); A. Pattie (Alison); K. Petrovic (Katja); Pulkki-R'back, L. (Laura); L. Quaye (Lydia); R'ikkönen, K. (Katri); I. Rudan (Igor); R. Scott (Rodney); J.A. Smith (Jennifer A); A.R. Sutin; Trzaskowski, M. (Maciej); Vinkhuyze, A.E. (Anna E.); L. Yu (Lei); D. Zabaneh (Delilah); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); D.I. Boomsma (Dorret); H. Snieder (Harold); Chang, S.-C. (Shun-Chiao); F. Cucca (Francesco); I.J. Deary (Ian J.); C.M. van Duijn (Cornelia); K. Hagen (Knut); U. Bültmann (Ute); E.J.C. de Geus (Eco); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); T. Hansen (T.); Hartman, C.A. (Catharine A); C.M.A. Haworth (Claire M.); C. Hayward (Caroline); A.C. Heath (Andrew C.); D.A. Hinds (David A.); E. Hypponen (Elina); W.G. Iacono (William); M.-R. Jarvelin (Marjo-Riitta); K.-H. JöCkel (Karl-Heinz); J. Kaprio (Jaakko); S.L.R. Kardia (Sharon); Keltikangas-J'rvinen, L. (Liisa); P. Kraft (Peter); Kubzansky, L.D. (Laura D.); Lehtim'ki, T. (Terho); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); A. Metspalu (Andres); M. Mills (Melinda); R. de Mutsert (Reneé); A.J. Oldehinkel (Albertine); G. Pasterkamp (Gerard); N.L. Pedersen (Nancy); R. Plomin (Robert); O. Polasek (Ozren); C. Power (Christopher); S.S. Rich (Stephen); F.R. Rosendaal (Frits); H.M. den Ruijter (Hester ); Schlessinger, D. (David); R. Schmidt (Reinhold); R. Svento (Rauli); R. Schmidt (Reinhold); B.Z. Alizadeh (Behrooz); T.I.A. Sørensen (Thorkild); DSpector, T. (Tim); Steptoe, A. (Andrew); A. Terracciano; A.R. Thurik (Roy); N.J. Timpson (Nicholas); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); P. Vollenweider (Peter); Wagner, G.G. (Gert G.); D.R. Weir (David); J. Yang (Joanna); Conley, D.C. (Dalton C.); G.D. Smith; Hofman, A. (Albert); M. Johannesson (Magnus); D. Laibson (David); S.E. Medland (Sarah Elizabeth); M.N. Meyer (Michelle N.); Pickrell, J.K. (Joseph K.); Esko, T. (T'nu); R.F. Krueger; J.P. Beauchamp (Jonathan); Ph.D. Koellinger (Philipp); D.J. Benjamin (Daniel J.); M. Bartels (Meike); D. Cesarini (David)

    2016-01-01

    textabstractVery few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data.

  11. Association between osteoporosis and urinary calculus: evidence from a population-based study.

    Science.gov (United States)

    Keller, J J; Lin, C-C; Kang, J-H; Lin, H-C

    2013-02-01

    This population-based case-control analysis investigated the association between osteoporosis and prior urinary calculus (UC) in Taiwan. We succeeded in detecting an association between osteoporosis and prior UC (adjusted odds ratio = 1.66). This association was consistent and significant regardless of stone location. UC has been demonstrated to be a risk factor for osteoporotic fractures, but no studies to date have directly investigated the association between UC and osteoporosis. This case-control analysis aimed to investigate the association of osteoporosis with prior UC using a population-based dataset in Taiwan. We first identified 39,840 cases ≥40 years who received their first-time diagnosis of osteoporosis between 2002 and 2009 and then randomly selected 79,680 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and the corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. The OR of having been previously diagnosed with UC for patients with osteoporosis was 1.66 (95 % CI = 1.59-1.73) when compared to controls after adjusting for geographic location, urbanization level, type I diabetes mellitus, coronary heart disease, hyperlipidemia, rheumatoid arthritis, stroke, renal disease, Parkinson's disease, hyperthyroidism, chronic hepatopathy, Cushing's syndrome, malabsorption, gastrectomy, obesity, and alcohol abuse/alcohol dependence syndrome. The results consistently showed that osteoporosis was significantly associated with a previous diagnosis of UC regardless of stone location; the adjusted ORs of prior kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.71 (95 % CI = 1.61-1.81), 1.60 (95 % CI = 1.47-1.74), 1.59 (95 % CI = 1.23-2.04), and 1.69 (95 % CI = 1.59-1.80), respectively. This study succeeded in detecting an association between osteoporosis and prior UC. In addition

  12. Improved score statistics for meta-analysis in single-variant and gene-level association studies.

    Science.gov (United States)

    Yang, Jingjing; Chen, Sai; Abecasis, Gonçalo

    2018-06-01

    Meta-analysis is now an essential tool for genetic association studies, allowing them to combine large studies and greatly accelerating the pace of genetic discovery. Although the standard meta-analysis methods perform equivalently as the more cumbersome joint analysis under ideal settings, they result in substantial power loss under unbalanced settings with various case-control ratios. Here, we investigate the power loss problem by the standard meta-analysis methods for unbalanced studies, and further propose novel meta-analysis methods performing equivalently to the joint analysis under both balanced and unbalanced settings. We derive improved meta-score-statistics that can accurately approximate the joint-score-statistics with combined individual-level data, for both linear and logistic regression models, with and without covariates. In addition, we propose a novel approach to adjust for population stratification by correcting for known population structures through minor allele frequencies. In the simulated gene-level association studies under unbalanced settings, our method recovered up to 85% power loss caused by the standard methods. We further showed the power gain of our methods in gene-level tests with 26 unbalanced studies of age-related macular degeneration . In addition, we took the meta-analysis of three unbalanced studies of type 2 diabetes as an example to discuss the challenges of meta-analyzing multi-ethnic samples. In summary, our improved meta-score-statistics with corrections for population stratification can be used to construct both single-variant and gene-level association studies, providing a useful framework for ensuring well-powered, convenient, cross-study analyses. © 2018 WILEY PERIODICALS, INC.

  13. Radiometric analyses of floodplain sediments at the Savannah River Plant

    International Nuclear Information System (INIS)

    Lower, M.W.

    1987-09-01

    A Comprehensive Cooling Water Study to assess the effects of reactor cooling water discharges and related reactor area liquid releases to onsite streams and the nearby Savannah River has been completed at the US Department of Energy's Savannah River Plant (SRP). Extensive radiometric analyses of man-made and naturally occurring gamma-emitting radionuclides were measured in floodplain sediment cores extracted from onsite surface streams at SRP and from the Savannah River. Gamma spectrometric analyses indicate that reactor operations contribute to floodplain radioactivity levels slightly higher than levels associated with global fallout. In locations historically unaffected by radioactive releases from SRP operations, Cs-137 concentrations were found at background and fallout levels of about 1 pCi/g. In onsite streams that provided a receptor for liquid radioactive releases from production reactor areas, volume-weighted Cs-137 concentrations ranged by core from background levels to 55 pCi/g. Savannah River sediments contained background and atmospheric fallout levels of Cs-137 only. 2 refs., 5 figs

  14. Genetic analyses of bolting in bulb onion (Allium cepa L.).

    Science.gov (United States)

    Baldwin, Samantha; Revanna, Roopashree; Pither-Joyce, Meeghan; Shaw, Martin; Wright, Kathryn; Thomson, Susan; Moya, Leire; Lee, Robyn; Macknight, Richard; McCallum, John

    2014-03-01

    We present the first evidence for a QTL conditioning an adaptive trait in bulb onion, and the first linkage and population genetics analyses of candidate genes involved in photoperiod and vernalization physiology. Economic production of bulb onion (Allium cepa L.) requires adaptation to photoperiod and temperature such that a bulb is formed in the first year and a flowering umbel in the second. 'Bolting', or premature flowering before bulb maturation, is an undesirable trait strongly selected against by breeders during adaptation of germplasm. To identify genome regions associated with adaptive traits we conducted linkage mapping and population genetic analyses of candidate genes, and QTL analysis of bolting using a low-density linkage map. We performed tagged amplicon sequencing of ten candidate genes, including the FT-like gene family, in eight diverse populations to identify polymorphisms and seek evidence of differentiation. Low nucleotide diversity and negative estimates of Tajima's D were observed for most genes, consistent with purifying selection. Significant population differentiation was observed only in AcFT2 and AcSOC1. Selective genotyping in a large 'Nasik Red × CUDH2150' F2 family revealed genome regions on chromosomes 1, 3 and 6 associated (LOD > 3) with bolting. Validation genotyping of two F2 families grown in two environments confirmed that a QTL on chromosome 1, which we designate AcBlt1, consistently conditions bolting susceptibility in this cross. The chromosome 3 region, which coincides with a functionally characterised acid invertase, was not associated with bolting in other environments, but showed significant association with bulb sucrose content in this and other mapping pedigrees. These putative QTL and candidate genes were placed on the onion map, enabling future comparative studies of adaptive traits.

  15. Joint associations of insomnia and sleep duration with prevalent diabetes: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    Science.gov (United States)

    Cespedes, Elizabeth M; Dudley, Katherine A; Sotres-Alvarez, Daniela; Zee, Phyllis C; Daviglus, Martha L; Shah, Neomi A; Talavera, Gregory A; Gallo, Linda C; Mattei, Josiemer; Qi, Qibin; Ramos, Alberto R; Schneiderman, Neil; Espinoza-Giacinto, Rebeca A; Patel, Sanjay R

    2016-05-01

    Inadequate sleep quantity and quality are associated with a higher risk of type 2 diabetes. This relationship is not well-examined in U.S. Hispanics/Latinos, and prior analyses may be confounded by sleep apnea. This cross-sectional study examined joint associations of sleep duration and insomnia with diabetes among diverse U.S. Hispanic/Latinos. Baseline data on sleep quantity and quality were obtained from 15,227 participants (mean age 41; range 18-74 years) from the Hispanic Community Health Study/Study of Latinos. Complex survey multinomial logistic regression was used to examine associations between prevalent diabetes and six phenotypes defined by cross-classifying sleep duration (short ≤6 h, average >6-9 h, long >9 h) and insomnia, adjusting for sex, age, site and Hispanic/Latino background interaction, education, physical activity, diet quality, and sleep apnea. In the weighted population, 14% had diabetes, 28% had insomnia, 9% were short sleepers, and 19% were long sleepers. Compared with those with average sleep and no insomnia, those with short sleep and insomnia were more likely to have diabetes (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.02, 2.11). Average sleepers with insomnia (1.28; 95% CI 1.02, 1.61) and long sleepers without insomnia (1.33; 95% CI 1.07, 1.65) also had elevated odds of diabetes. Further adjustment for body mass index attenuated associations, except with long sleep without insomnia. Both decreased quantity and quality of sleep are associated with diabetes in Hispanic/Latinos, with the greatest odds among those with short sleep duration and insomnia. The association is largely explained by obesity. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  16. Walkability and cardiometabolic risk factors: Cross-sectional and longitudinal associations from the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Braun, Lindsay M; Rodríguez, Daniel A; Evenson, Kelly R; Hirsch, Jana A; Moore, Kari A; Diez Roux, Ana V

    2016-05-01

    We used data from 3227 older adults in the Multi-Ethnic Study of Atherosclerosis (2004-2012) to explore cross-sectional and longitudinal associations between walkability and cardiometabolic risk factors. In cross-sectional analyses, linear regression was used to estimate associations of Street Smart Walk Score® with glucose, triglycerides, HDL and LDL cholesterol, systolic and diastolic blood pressure, and waist circumference, while logistic regression was used to estimate associations with odds of metabolic syndrome. Econometric fixed effects models were used to estimate longitudinal associations of changes in walkability with changes in each risk factor among participants who moved residential locations between 2004 and 2012 (n=583). Most cross-sectional and longitudinal associations were small and statistically non-significant. We found limited evidence that higher walkability was cross-sectionally associated with lower blood pressure but that increases in walkability were associated with increases in triglycerides and blood pressure over time. Further research over longer time periods is needed to understand the potential for built environment interventions to improve cardiometabolic health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Association of perceived neighborhood characteristics, socioeconomic status and rural residency with health outcomes in Egyptian patients with systemic lupus erythematosus: one center study.

    Science.gov (United States)

    Abdul-Sattar, Amal B; Abou El Magd, Sahar

    2017-12-01

    To investigate the role of perceived neighborhood characteristics, socioeconomic status (SES) and rural residency in influencing the health status outcome of Egyptian patients with systemic lupus erythematosus (SLE). Eighty patients affected with SLE were consecutively included in this a single-center cross-sectional study from July, 2011 to July, 2013. Outcome measures included the Systemic Lupus Activity Questionnaire (SLAQ) score, the Medical Outcomes Study Short Form-36 Health Survey physical functioning score and Center for Epidemiologic Studies-Depression (CES-D score of ≥ 19 points). Multivariate logistic regression analyses were conducted. Results from multivariate logistic regression analyses, a separate adjusted model of each perceived neighborhood characteristic, indicate associations of worse perceived social cohesion with higher SLAQ scores (P socioeconomic status and rural residency with health status outcomes, the results found association of poor socioeconomic status with the three health status outcome measures and association between rural residency and depression symptoms. Individuals had increased odds of depressive symptoms if they perceived worse neighborhood social cohesion (odds ratio [OR]: 2.14; CI: 1.42-2.80), if they perceived worse neighborhood safety (OR: 1.64; CI: 1.02-2.40) and if they perceived worse neighborhood aesthetic characteristics (OR: 2.79; CI: 1.84-3.38). Study findings indicate that poor socioeconomic status, rural residency and perceived neighborhood characteristics are associated with depression; worse perceived neighborhood aesthetics and safety are associated with lower SF-36 physical functioning, and worse neighborhood social cohesion is associated with higher disease activity among patients with SLE. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  18. The Gutenberg health study: associations between occupational and private stress factors and work-privacy conflict.

    Science.gov (United States)

    Garthus-Niegel, Susan; Hegewald, Janice; Seidler, Andreas; Nübling, Matthias; Espinola-Klein, Christine; Liebers, Falk; Wild, Philipp S; Latza, Ute; Letzel, Stephan

    2016-02-29

    Work-privacy conflict (WPC) is no longer a rarity but constitutes a societal problem. The objectives of the present study were (1) to investigate the distribution and prevalence of WPC among the employed participants in the Gutenberg Health Study at baseline and (2) to study the dependence of WPC on a broad range of private life and occupational characteristics as well as on psychosocial working conditions. This analysis is based on a representative, population-based sample of 3,709 employees participating in the Gutenberg Health Study. Descriptive and bivariable analyses were carried out separately for women and men. Distribution and prevalence of WPC were examined according to socio-demographic and occupational characteristics as well as psychosocial working conditions. Further, stepwise selection of Poisson log-linear regression models were performed to determine which socio-demographic and occupational characteristics were most associated with the outcome variable WPC and to obtain adjusted prevalence ratios from the final model. The multivariable analyses were conducted both separately for women and men and with all subjects together in one analysis. There was a high prevalence of WPC in the present study (27.4 % of the men and 23.0 % of the women reported a high or very high WPC). A variety of factors was associated with WPC, e.g. full-time employment, depression and many of the psychosocial risk factors at work. Also, the multivariable results showed that women were of higher risk for a WPC. By affecting the individual work life, home life, and the general well-being and health, WPC may lead to detrimental effects in employees, their families, employers, and society as a whole. Therefore, the high prevalence of WPC in our sample should be of concern. Among women, the risk for suffering from WPC was even higher, most likely due to multiple burdens.

  19. Admission interview scores are associated with clinical performance in an undergraduate physiotherapy course: an observational study.

    Science.gov (United States)

    Edgar, Susan; Mercer, Annette; Hamer, Peter

    2014-12-01

    The purpose of this study was to determine if there is an association between admission interview score and subsequent academic and clinical performance, in a four-year undergraduate physiotherapy course. Retrospective observational study. 141 physiotherapy students enrolled in two entry year groups. Individual student performance in all course units, practical examinations, clinical placements as well as year level and overall Grade Point Average. Predictor variables included admission interview scores, admission academic scores and demographic data (gender, age and entry level). Interview score demonstrated a significant association with performance in three of six clinical placements through the course. This association was stronger than for any other admission criterion although effect sizes were small to moderate. Further, it was the only admission score to have a significant association with overall Clinical Grade Point Average for the two year groups analysed (r=0.322). By contrast, academic scores on entry showed significant associations with all year level Grade Point Averages except Year 4, the clinical year. This is the first study to review the predictive validity of an admission interview for entry into a physiotherapy course in Australia. The results show that performance in this admission interview is associated with overall performance in clinical placements through the course, while academic admission scoring is not. These findings suggest that there is a role for both academic and non-academic selection processes for entry into physiotherapy. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  20. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

    NARCIS (Netherlands)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel G; Fontana, Mark Alan; Meddens, S Fleur W; Linnér, Richard Karlsson; Rietveld, Cornelius A; Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Miller, Michael B; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davies, Gail; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Steptoe, Andrew; Terracciano, Antonio; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted

  1. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.

    NARCIS (Netherlands)

    Okbay, A.; Baselmans, B.M.L.; de Neve, J.E.; Turley, P.; Nivard, M.G.; Fontana, M.A.; Meddens, S.F.W.; Karlsson Linnér, R.; Rietveld, C.A.; Derringer, J.; de Vlaming, R.; Minica, C.C.; Hottenga, J.J.; Vinkhuyzen, A.A.E.; Boomsma, D.I.; de Geus, E.J.C.; Medland, S.E.; Meyer, M.N.; Pickrell, J.K.; Esko, T.; Krueger, R.F.; Beauchamp, J.; Koellinger, P.D.; Benjamin, D.J.; Bartels, M.; Cesarini, D.

    2016-01-01

    Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted

  2. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    NARCIS (Netherlands)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian'an; Maegi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segre, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpelaenen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tonu; Feitosa, Mary F.; Kutalik, Zoltan; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; van Meurs, Joyce B. J.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of

  3. Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study.

    Directory of Open Access Journals (Sweden)

    Ragnhild E Brandlistuen

    Full Text Available During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD and z-hypnotic use during pregnancy remains controversial.We conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings at 1.5 years and 55,081 children (13,779 siblings at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression and other potential confounding factors.Long-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models [β 0.60, 95% confidence interval 0.17-0.95]. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years [β 0.25, 0.01-0.49] and 3 years [β 0.26, 0.002-0.52] while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment.The findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is

  4. Hearing loss among older construction workers: Updated analyses.

    Science.gov (United States)

    Dement, John; Welch, Laura S; Ringen, Knut; Cranford, Kim; Quinn, Patricia

    2018-04-01

    A prior study of this construction worker population found significant noise-associated hearing loss. This follow-up study included a much larger study population and consideration of additional risk factors. Data included audiometry, clinical chemistry, personal history, and work history. Qualitative exposure metrics for noise and solvents were developed. Analyses compared construction workers to an internal reference group with lower exposures and an external worker population with low noise exposure. Among participants (n = 19 127) an overall prevalence of hearing loss of 58% was observed, with significantly increased prevalence across all construction trades. Construction workers had significantly increased risk of hearing loss compared to reference populations, with increasing risk by work duration. Noise exposure, solvent exposure, hypertension, and smoking were significant risk factors in multivariate models. Results support a causal relationship between construction trades work and hearing loss. Prevention should focus on reducing exposure to noise, solvents, and cigarette smoke. © 2018 Wiley Periodicals, Inc.

  5. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC.

    Directory of Open Access Journals (Sweden)

    Rebecca Hein

    Full Text Available The 6q25.1 locus was first identified via a genome-wide association study (GWAS in Chinese women and marked by single nucleotide polymorphism (SNP rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR and 95% confidence intervals (CI. Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+ versus negative (ER- tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G = 1.36 (95% CI 1.26-1.48, p = 7.6 × 10(-14 in Asians and 1.09 (95% CI 1.07-1.11, p = 6.8 × 10(-18 in Europeans. rs12662670: OR (G/T = 1.29 (95% CI 1.19-1.41, p = 1.2 × 10(-9 in Asians and 1.12 (95% CI 1.08-1.17, p = 3.8 × 10(-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER- = 1.20 (95% CI 1.15-1.25, p = 1.8 × 10(-17 versus OR (ER+ = 1.07 (95% CI 1.04-1.1, p = 1.3 × 10(-7, p(heterogeneity = 5.1 × 10(-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater

  6. Genome-wide association study for ketosis in US Jerseys using producer-recorded data.

    Science.gov (United States)

    Parker Gaddis, K L; Megonigal, J H; Clay, J S; Wolfe, C W

    2018-01-01

    Ketosis is one of the most frequently reported metabolic health events in dairy herds. Several genetic analyses of ketosis in dairy cattle have been conducted; however, few have focused specifically on Jersey cattle. The objectives of this research included estimating variance components for susceptibility to ketosis and identification of genomic regions associated with ketosis in Jersey cattle. Voluntary producer-recorded health event data related to ketosis were available from Dairy Records Management Systems (Raleigh, NC). Standardization was implemented to account for the various acronyms used by producers to designate an incidence of ketosis. Events were restricted to the first reported incidence within 60 d after calving in first through fifth parities. After editing, there were a total of 42,233 records from 23,865 cows. A total of 1,750 genotyped animals were used for genomic analyses using 60,671 markers. Because of the binary nature of the trait, a threshold animal model was fitted using THRGIBBS1F90 (version 2.110) using only pedigree information, and genomic information was incorporated using a single-step genomic BLUP approach. Individual single nucleotide polymorphism (SNP) effects and the proportion of variance explained by 10-SNP windows were calculated using postGSf90 (version 1.38). Heritability of susceptibility to ketosis was 0.083 [standard deviation (SD) = 0.021] and 0.078 (SD = 0.018) in pedigree-based and genomic analyses, respectively. The marker with the largest associated effect was located on chromosome 10 at 66.3 Mbp. The 10-SNP window explaining the largest proportion of variance (0.70%) was located on chromosome 6 beginning at 56.1 Mbp. Gene Ontology (GO) and Medical Subject Heading (MeSH) enrichment analyses identified several overrepresented processes and terms related to immune function. Our results indicate that there is a genetic component related to ketosis susceptibility in Jersey cattle and, as such, genetic selection for

  7. The Association between Residence Floor Level and Cardiovascular Disease: The Health and Environment in Oslo Study.

    Science.gov (United States)

    Rohde, Mads K; Aamodt, Geir

    2016-01-01

    Background. Increasingly more people live in tall buildings and on higher floor levels. Factors relating to floor level may protect against or cause cardiovascular disease (CVD). Only one previous study has investigated the association between floor level and CVD. Methods. We studied associations between floor of bedroom and self-reported history of stroke, venous thromboembolism (VTE), and intermittent claudication (IC) among 12.525 inhabitants in Oslo, Norway. We fitted multivariate logistic regression models and adjusted for sociodemographic variables, socioeconomic status (SES), and health behaviors. Additionally, we investigated block apartment residents ( N = 5.374) separately. Results. Trend analyses showed that disease prevalence increased by floor level, for all three outcomes. When we investigated block apartment residents alone, the trends disappeared, but one association remained: higher odds of VTE history on 6th floor or higher, compared to basement and 1st floor (OR: 1.504; 95% CI: 1.007-2.247). Conclusion. Floor level is positively associated with CVD, in Oslo. The best-supported explanation may be residual confounding by building height and SES. Another explanation, about the impact of atmospheric electricity, is also presented. The results underline a need to better understand the associations between residence floor level and CVD and multistory housing and CVD.

  8. Association between serum interleukin-6 concentrations and mortality in older adults: the Rancho Bernardo study.

    Directory of Open Access Journals (Sweden)

    Jeffrey K Lee

    Full Text Available Interleukin-6 (IL-6 may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD, cancer, and liver-related mortality.A prospective cohort study included 1843 participants who attended a research visit in 1984-87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality.The mean (± standard deviation age and body-mass-index (BMI of participants was 68 (± 10.6 years and 25 (± 3.7 Kg/m(2, respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978, 25.5%, 11.3%, and 1.3%, respectively. The median (± IQR length of follow-up was 15.3 ± 10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33-1.64, 1.38 (95% CI, 1.16-1.65, 1.35 (95% CI, 1.02-1.79, and 1.88 (95% CI, 0.97-3.67, respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels.In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.

  9. Cross-sectional associations of active transport, employment status and objectively measured physical activity: analyses from the National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Yang, Lin; Hu, Liang; Hipp, J Aaron; Imm, Kellie R; Schutte, Rudolph; Stubbs, Brendon; Colditz, Graham A; Smith, Lee

    2018-05-05

    To investigate associations between active transport, employment status and objectively measured moderate-to-vigorous physical activity (MVPA) in a representative sample of US adults. Cross-sectional analyses of data from the National Health and Nutrition Examination Survey. A total of 5180 adults (50.2 years old, 49.0% men) were classified by levels of active transportation and employment status. Outcome measure was weekly time spent in MVPA as recorded by the Actigraph accelerometer. Associations between active transport, employment status and objectively measured MVPA were examined using multivariable linear regression models adjusted for age, body mass index, race and ethnicity, education level, marital status, smoking status, working hour duration (among the employed only) and self-reported leisure time physical activity. Patterns of active transport were similar between the employed (n=2897) and unemployed (n=2283), such that 76.0% employed and 77.5% unemployed engaged in no active transport. For employed adults, those engaging in high levels of active transport (≥90 min/week) had higher amount of MVPA than those who did not engage in active transport. This translated to 40.8 (95% CI 15.7 to 65.9) additional minutes MVPA per week in men and 57.9 (95% CI 32.1 to 83.7) additional minutes MVPA per week in women. Among the unemployed adults, higher levels of active transport were associated with more MVPA among men (44.8 min/week MVPA, 95% CI 9.2 to 80.5) only. Findings from the present study support interventions to promote active transport to increase population level physical activity. Additional strategies are likely required to promote physical activity among unemployed women. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Study on the atmospheric component with the scope of analyses on the environmental impact

    International Nuclear Information System (INIS)

    Ferrara, V.; La Camera, F.

    1989-03-01

    This work has been carried out following a specific request from Italian National Department for Environment and shows technical approaches and methodologies of analyses and forecasts set up for environmental impact studies referred to 'atmospheric environment'. This work is presented according to the general items and objectives fixed by the same Department in the wider operative system for the application in Italy of environmental impact procedures. (author)

  11. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Minna M Boström

    Full Text Available Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker, MAC387 (polarized towards type 1 macrophages, and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection.

  12. Mapping the sensory perception of apple using descriptive sensory evaluation in a genome wide association study.

    Science.gov (United States)

    Amyotte, Beatrice; Bowen, Amy J; Banks, Travis; Rajcan, Istvan; Somers, Daryl J

    2017-01-01

    Breeding apples is a long-term endeavour and it is imperative that new cultivars are selected to have outstanding consumer appeal. This study has taken the approach of merging sensory science with genome wide association analyses in order to map the human perception of apple flavour and texture onto the apple genome. The goal was to identify genomic associations that could be used in breeding apples for improved fruit quality. A collection of 85 apple cultivars was examined over two years through descriptive sensory evaluation by a trained sensory panel. The trained sensory panel scored randomized sliced samples of each apple cultivar for seventeen taste, flavour and texture attributes using controlled sensory evaluation practices. In addition, the apple collection was subjected to genotyping by sequencing for marker discovery. A genome wide association analysis suggested significant genomic associations for several sensory traits including juiciness, crispness, mealiness and fresh green apple flavour. The findings include previously unreported genomic regions that could be used in apple breeding and suggest that similar sensory association mapping methods could be applied in other plants.

  13. Mapping the sensory perception of apple using descriptive sensory evaluation in a genome wide association study

    Science.gov (United States)

    Amyotte, Beatrice; Bowen, Amy J.; Banks, Travis; Rajcan, Istvan; Somers, Daryl J.

    2017-01-01

    Breeding apples is a long-term endeavour and it is imperative that new cultivars are selected to have outstanding consumer appeal. This study has taken the approach of merging sensory science with genome wide association analyses in order to map the human perception of apple flavour and texture onto the apple genome. The goal was to identify genomic associations that could be used in breeding apples for improved fruit quality. A collection of 85 apple cultivars was examined over two years through descriptive sensory evaluation by a trained sensory panel. The trained sensory panel scored randomized sliced samples of each apple cultivar for seventeen taste, flavour and texture attributes using controlled sensory evaluation practices. In addition, the apple collection was subjected to genotyping by sequencing for marker discovery. A genome wide association analysis suggested significant genomic associations for several sensory traits including juiciness, crispness, mealiness and fresh green apple flavour. The findings include previously unreported genomic regions that could be used in apple breeding and suggest that similar sensory association mapping methods could be applied in other plants. PMID:28231290

  14. Association of smoking and snuffing with dental caries occurrence in a young male population in Finland: a cross-sectional study.

    Science.gov (United States)

    Tanner, Tarja; Kämppi, Antti; Päkkilä, Jari; Järvelin, Marjo-Riitta; Patinen, Pertti; Tjäderhane, Leo; Anttonen, Vuokko

    2014-11-01

    The aim of this study was to investigate the prevalence of smoking and snuffing habits in association with dental caries occurrence in a male cohort born in the early 1990s in Finland. The impact of health behaviours and factors related to the place of residence were included in analyses. Oral health of 8537 conscripts was screened in a cross-sectional study. In the same occasion they also answered a questionnaire covering their smoking and snuffing habits and other background factors. The residence-related factors were obtained from the Defence Forces' database. Cross-tabulation together with chi-squared test and generalized linear mixed models were used for analyses. Almost forty per cent (39.4%) of the men reported smoking daily and 9.0% reported daily snuffing. Restorative treatment need of those who reported frequent smoking was more than 2-fold (mean DT = 2.22) compared to the non-smokers (mean DT = 1.07). Smoking was statistically significantly associated with other harmful health behaviours. The snuffers reported more snacking than the non-smokers, but were most frequent brushers. The result from the statistical modelling showed that smoking, low tooth brushing frequency, eating sweets and consuming energy drinks frequently were significantly associated with restorative treatment need. In this cross-sectional study, association between smoking and dental caries was distinct. The high rate of restorative treatment need among smokers may be explained by their poor health behaviours. Dietary habits of the snuffers seem harmful too, but are compensated by good tooth brushing frequency.

  15. Factors associated with complications of removal of third molars: a transversal study.

    Science.gov (United States)

    Barbosa-Rebellato, Nelson-Luis; Thomé, Ana-Carolina; Costa-Maciel, Cássia; Oliveira, Jaina; Scariot, Rafaela

    2011-05-01

    The purpose of this study is to estimate the overall frequency of complications associated with third molars (M3) removal and to identify the risk factors associated with these complications. To the transversal analysis, a researcher confidentially reviewed the records of all M3 surgery patients. The predictor variables were demographic (i.e. age and gender), localization and position of third molar, bone removal and tooth sectioning. 210 patients had one or more third molars teeth removed, a total of 605 teeth. The sample's mean age was 21.6±9.2 years, with 1,4 woman to 1 man. Postoperative complications were recorded in 54 extractions of third molars. The most common complications were infection (42.6%), followed by radicular fractures (11.1%) and gingival alterations (11.1%). Complications were significantly affected by 3 factors: age over 25 years old (p=0.002--OR 2.21), location (p=0.006--OR 2.36), bone removal (p=0.002--OR 3.03) and tooth sectioning (p=0.00002--OR 3.59). The results of these analyses suggest that age, location of the tooth, bone removal and tooth sectioning appear to be associated with a higher complication rate for M3 extractions.

  16. Association between air pollution and hospital admission: Case study at three monitoring stations in Malaysia

    Science.gov (United States)

    Zahari, Marina; Zin@Ibrahim, Wan Zawiah Wan; Ismail, Noriszura; Ni, Tan Hui

    2014-06-01

    The relationships between the exposure of pollutants towards hospitalized admission and mortality have been identified in several studies on Asian cities such as Taipei, Bangkok and Tokyo. In Malaysia, evidence on the health risks associated with exposure to pollutants is limited. In this study, daily time-series data were analysed to estimate risks of cardiovascular and respiratory hospitalized admissions associated with particulate matter ≤ 10 μm (PM10), carbon monoxide (CO), nitrogen dioxide, sulphur dioxide, and ozone concentrations in Klang Valley during 2004-2009. Daily counts of hospital admissions for cardiovascular and respiratory outcomes were obtained from eleven hospitals while pollutants data were taken from several air quality monitoring stations located nearest to the hospitals. These data were fitted with Generalised Additive Poisson regression models. Additionally, temperature, humidity, and time data were also included to allow for potential effect of weather and time-varying influences on hospital admissions. CO showed the most significant (P Malaysia.

  17. The association of depression and anxiety with pain: a study from NESDA.

    Directory of Open Access Journals (Sweden)

    Eric W de Heer

    Full Text Available Chronic pain is commonly co-morbid with a depressive or anxiety disorder. Objective of this study is to examine the influence of depression, along with anxiety, on pain-related disability, pain intensity, and pain location in a large sample of adults with and without a depressive and/or anxiety disorder. The study population consisted of 2981 participants with a depressive, anxiety, co-morbid depressive and anxiety disorder, remitted disorder or no current disorder (controls. Severity of depressive and anxiety symptoms was also assessed. In separate multinomial regression analyses, the association of presence of depressive or anxiety disorders and symptom severity with the Chronic Pain Grade and location of pain was explored. Presence of a depressive (OR = 6.67; P<.001, anxiety (OR = 4.84; P<.001, or co-morbid depressive and anxiety disorder (OR = 30.26; P<.001 was associated with the Chronic Pain Grade. Moreover, symptom severity was associated with more disabling and severely limiting pain. Also, a remitted depressive or anxiety disorder showed more disabling and severely limiting pain (OR = 3.53; P<.001 as compared to controls. A current anxiety disorder (OR = 2.96; p<.001 and a co-morbid depressive and anxiety disorder (OR = 5.15; P<.001 were more strongly associated with cardio-respiratory pain, than gastro-intestinal or musculoskeletal pain. These findings remain after adjustment for chronic cardio respiratory illness. Patients with a current and remitted depressive and/or anxiety disorder and those with more severe symptoms have more disabling pain and pain of cardio-respiratory nature, than persons without a depressive or anxiety disorder. This warrants further research.

  18. Genome-wide association study identifies candidate genes for starch content regulation in maize kernels

    Directory of Open Access Journals (Sweden)

    Na Liu

    2016-07-01

    Full Text Available Kernel starch content is an important trait in maize (Zea mays L. as it accounts for 65% to 75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60% to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001, among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437 is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops.

  19. Association between infection with Helicobacter pylori and atopy in young Ethiopian children: A longitudinal study.

    Science.gov (United States)

    Taye, B; Enquselassie, F; Tsegaye, A; Amberbir, A; Medhin, G; Fogarty, A; Robinson, K; Davey, G

    2017-10-01

    Epidemiological evidence from developed countries indicates that Helicobacter pylori infection correlates with a reduced risk of atopy and allergic disorders; however, limited data are available from low-income countries. We examined associations between H. pylori infection in early childhood and atopy and reported allergic disorders at the age of 6.5 years in an Ethiopian birth cohort. A total of 856 children (85.1% of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half years. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Questions on allergic disease symptoms were based on the International Study of Asthma and Allergies in Children (ISAAC) core allergy and environmental questionnaire. Serum samples were analysed for total IgE levels and anti-H. pylori cytotoxin-associated gene A (CagA) IgG antibody using commercially available ELISA kits. Stool samples were analysed for H. pylori antigen using a rapid immunochromatographic test. The independent effects of H. pylori infection (measured at age of 3, 5 and 6.5 years) on prevalence and incidence of atopy and reported allergic disorders (measured at age of 6.5 years) were determined using multiple logistic regression. In cross-sectional analysis, current H. pylori infection at age 6.5 years was inversely, though not significantly, related to prevalence of atopy and "any allergic condition" at age 6.5 years. However, detection of H. pylori infection at any point up to age 6.5 years was associated with a significantly reduced odds of both atopy and "any allergic condition" (adjusted OR AOR, 95% CI, 0.54; 0.32-0.92, P = .02, and .31; 0.10-0.94, P = .04, respectively). In longitudinal analyses, H. pylori infection at age 3 was inversely associated with incidence of atopy (AOR, 95% CI, 0.49; 0.27-0.89, P = .02). Furthermore, among H. pylori-infected children, those with a Cag

  20. Genome-wide association study identified copy number variants important for appendicular lean mass.

    Science.gov (United States)

    Ran, Shu; Liu, Yong-Jun; Zhang, Lei; Pei, Yufang; Yang, Tie-Lin; Hai, Rong; Han, Ying-Ying; Lin, Yong; Tian, Qing; Deng, Hong-Wen

    2014-01-01

    Skeletal muscle is a major component of the human body. Age-related loss of muscle mass and function contributes to some public health problems such as sarcopenia and osteoporosis. Skeletal muscle, mainly composed of appendicular lean mass (ALM), is a heritable trait. Copy number variation (CNV) is a common type of human genome variant which may play an important role in the etiology of many human diseases. In this study, we performed genome-wide association analyses of CNV for ALM in 2,286 Caucasian subjects. We then replicated the major findings in 1,627 Chinese subjects. Two CNVs, CNV1191 and CNV2580, were detected to be associated with ALM (p = 2.26×10(-2) and 3.34×10(-3), respectively). In the Chinese replication sample, the two CNVs achieved p-values of 3.26×10(-2) and 0.107, respectively. CNV1191 covers a gene, GTPase of the immunity-associated protein family (GIMAP1), which is important for skeletal muscle cell survival/death in humans. CNV2580 is located in the Serine hydrolase-like protein (SERHL) gene, which plays an important role in normal peroxisome function and skeletal muscle growth in response to mechanical stimuli. In summary, our study suggested two novel CNVs and the related genes that may contribute to variation in ALM.

  1. Genome-wide association study identified copy number variants important for appendicular lean mass.

    Directory of Open Access Journals (Sweden)

    Shu Ran

    Full Text Available Skeletal muscle is a major component of the human body. Age-related loss of muscle mass and function contributes to some public health problems such as sarcopenia and osteoporosis. Skeletal muscle, mainly composed of appendicular lean mass (ALM, is a heritable trait. Copy number variation (CNV is a common type of human genome variant which may play an important role in the etiology of many human diseases. In this study, we performed genome-wide association analyses of CNV for ALM in 2,286 Caucasian subjects. We then replicated the major findings in 1,627 Chinese subjects. Two CNVs, CNV1191 and CNV2580, were detected to be associated with ALM (p = 2.26×10(-2 and 3.34×10(-3, respectively. In the Chinese replication sample, the two CNVs achieved p-values of 3.26×10(-2 and 0.107, respectively. CNV1191 covers a gene, GTPase of the immunity-associated protein family (GIMAP1, which is important for skeletal muscle cell survival/death in humans. CNV2580 is located in the Serine hydrolase-like protein (SERHL gene, which plays an important role in normal peroxisome function and skeletal muscle growth in response to mechanical stimuli. In summary, our study suggested two novel CNVs and the related genes that may contribute to variation in ALM.

  2. Association of surfactant protein-d with obesity

    International Nuclear Information System (INIS)

    Jawed, S.

    2016-01-01

    Obesity is associated with inflammatory diseases and obese individual's poses high risk for infections. Surfactant protein D (SP-D) is an important regulator of immunity and inflammation. Latest studies have suggested that it is also involved in lipid homeostasis and obese subjects have decrease concentration of SPD as compared to normal weight peoples. The aim of the current study was to elucidate the relationship among serum SP-D and BMI. Method: This cross sectional study was performed at Dow University of health sciences (DUHS), Karachi. We analysed 90 obese and non-obese subjects for serum SP-D concentration. SP-D was estimated by ELISA. Data was analysed by SPSS 16. Mean SP-D level and demographical variables between the groups were compared by t test, Associations of SP-D with BMI investigated by regression analysis. Results: obese subjects have significant lower levels of Serum SP-D than non-obese and negatively associated with BMI in both genders (p=0.000). Conclusion: This study concluded that obese subjects have lower concentration of SP-D as compare to non-obese and there is an inverse association between the SP-D and BMI. (author)

  3. Primary care physicians' adoption of new drugs is not associated with their clinical interests: A pharmacoepidemiologic study

    DEFF Research Database (Denmark)

    Dybdahl, Torben; Søndergaard, Jens; Kragstrup, Jakob

    2011-01-01

    Abstract Objectives. Increasing drug expenditures call for better understanding of the reasons behind individual general practitioners' (GPs') prescribing decisions. The aim was to analyse associations between GPs' clinical interests and their preference for new drugs. Design. Historical cohort...... association between GPs' self-rated clinical interest and their prescribing of new drugs was found.......-II antagonists) were analysed. The preference was defined as the percentage of patients receiving a new drug among first-time users of either the new drug or an older alternative. The GPs' preference proportion was modelled using linear regression analysis. Data from a questionnaire on GPs' interest...

  4. Mitogenomic analyses from ancient DNA

    DEFF Research Database (Denmark)

    Paijmans, Johanna L. A.; Gilbert, Tom; Hofreiter, Michael

    2013-01-01

    The analysis of ancient DNA is playing an increasingly important role in conservation genetic, phylogenetic and population genetic analyses, as it allows incorporating extinct species into DNA sequence trees and adds time depth to population genetics studies. For many years, these types of DNA...... analyses (whether using modern or ancient DNA) were largely restricted to the analysis of short fragments of the mitochondrial genome. However, due to many technological advances during the past decade, a growing number of studies have explored the power of complete mitochondrial genome sequences...... yielded major progress with regard to both the phylogenetic positions of extinct species, as well as resolving population genetics questions in both extinct and extant species....

  5. PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

    Science.gov (United States)

    Xu, Kuanfeng; Liu, Xiaoyun; Yang, Fan; Cui, Dai; Shi, Yun; Shen, Chong; Tang, Wei; Yang, Tao

    2013-01-01

    A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg's and Egger's test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies.

  6. Presence of the variant mannose-binding lectin alleles associated with slower progression to AIDS. Amsterdam Cohort Study

    NARCIS (Netherlands)

    Maas, J.; de Roda Husman, A. M.; Brouwer, M.; Krol, A.; Coutinho, R.; Keet, I.; van Leeuwen, R.; Schuitemaker, H.

    1998-01-01

    OBJECTIVE: To examine the association between mannose-binding lectin (MBL) polymorphism and progression to AIDS and death in HIV-1 infection. DESIGN AND METHODS: In 131 HIV-1-infected homosexual seroconverters, survival analyses were performed to determine both the association between MBL genotype

  7. Factors associated with remission of eczema in children: a population-based follow-up study.

    Science.gov (United States)

    von Kobyletzki, Laura B; Bornehag, Carl-Gustaf; Breeze, Elizabeth; Larsson, Malin; Lindström, Cecilia Boman; Svensson, Åke

    2014-03-01

    The aim of this study was to analyse factors associated with remission of atopic dermatitis (AD) in childhood. A population-based AD cohort of 894 children aged 1-3 years from a cross-sectional baseline study in 2000 was followed up in 2005. The association between remission, background, health, lifestyle, and environmental variables was estimated with crude and multivariable logistic regression. At follow-up, 52% of the children had remission. Independent factors at baseline predicting remission were: milder eczema (adjusted odds ratio (aOR), 1.43; 95% confidence interval (95% CI) 1.16-1.77); later onset of eczema (aOR 1.40; 95% CI 1.08-1.80); non-flexural eczema (aOR 2.57; 95% CI 1.62-4.09); no food allergy (aOR 1.51; 95% CI 1.11-2.04), and rural living (aOR 1.48; 95% CI 1.07-2.05). Certain aspects of AD and rural living were important for remission, but despite the initial hypotheses to the contrary, the environmental factors examined in this paper were not substantial predictors of remission.

  8. Dietary supplement use and colorectal cancer risk: A systematic review and meta-analyses of prospective cohort studies

    NARCIS (Netherlands)

    Heine-Bröring, R.C.; Winkels, R.M.; Renkema, J.M.S.; Kragt, L.; Orten-Luiten, van A.C.B.; Tigchelaar, E.F.; Chan, D.S.M.; Norat, T.; Kampman, E.

    2015-01-01

    Use of dietary supplements is rising in countries where colorectal cancer is prevalent. We conducted a systematic literature review and meta-analyses of prospective cohort studies on dietary supplement use and colorectal cancer risk. We identified relevant studies in Medline, Embase and Cochrane up

  9. Externalizing behavior in early childhood and body mass index from age 2 to 12 years: longitudinal analyses of a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Schoppe-Sullivan Sarah

    2010-07-01

    Full Text Available Abstract Background Some evidence suggests that obesity and behavior problems are related in children, but studies have been conflicting and have rarely included children under age 4. An association between behavior problems in early childhood and risk for obesity could suggest that a common set of factors contribute to both. Our research objectives were to determine the extent to which externalizing behavior in early childhood is related to body mass index (BMI in early childhood and through age 12, and to evaluate whether these associations differ by sex and race. Methods Data from the NICHD Study of Early Child Care and Youth Development were analyzed. Externalizing behaviors at 24 months were assessed by mothers using the Child Behavior Checklist. BMI was calculated from measured height and weight assessed 7 times between age 2 and 12 years. Linear mixed effects models were used to assess associations between 24 month externalizing behavior and BMI from 2 to 12 years, calculate predicted differences in BMI, and evaluate effect modification. Results Externalizing behavior at 24 months was associated with a higher BMI at 24 months and through age 12. Results from a linear mixed effects model, controlling for confounding variables and internalizing behavior, predicted a difference in BMI of approximately 3/4 of a unit at 24 months of age comparing children with high levels of externalizing behavior to children with low levels of externalizing behavior. There was some evidence of effect modification by race; among white children, the average BMI difference remained stable through age 12, but it doubled to 1.5 BMI units among children who were black or another race. Conclusions Our analyses suggest that externalizing behaviors in early childhood are associated with children's weight status early in childhood and throughout the elementary school years, though the magnitude of the effect is modest.

  10. Chronic Stress is Prospectively Associated with Sleep in Midlife Women: The SWAN Sleep Study.

    Science.gov (United States)

    Hall, Martica H; Casement, Melynda D; Troxel, Wendy M; Matthews, Karen A; Bromberger, Joyce T; Kravitz, Howard M; Krafty, Robert T; Buysse, Daniel J

    2015-10-01

    Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women. Prospective cohort study. Four sites across the United States. 330 women (46-57 y of age) enrolled in the Study of Women's Health Across the Nation (SWAN) Sleep Study. N/A. Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints. Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time. © 2015 Associated Professional Sleep Societies, LLC.

  11. Genome-Wide Association Study with Sequence Variants Identifies Candidate Genes for Mastitis Resistance in Dairy Cattle

    DEFF Research Database (Denmark)

    Sahana, Goutam; Guldbrandtsen, Bernt; Bendixen, Christian

    Six genomic regions affecting clinical mastitis were identified through a GWAS study with imputed BovineHD chip genotype data in the Nordic Holstein cattle population. The association analyses were carried out using a SNP-by-SNP analysis by fitting the regression of allele dosage and a polygenic...... Effect Predictor (VEP) vers. 2.6 using ENSEMBL vers. 67 databases. Candidate polymorphisms affecting clinical mastitis were selected based on their association with the traits and functional annotations. A strong positional candidate gene for mastitis resistance on chromosome-6 is the NPFFR2 which...... Factor Receptor Alpha (LIFR) emerged as a strong candidate gene for mastitis resistance. The LIFR gene is involved in acute phase response and is expressed in saliva and mammary gland....

  12. Genome association study through nonlinear mixed models revealed new candidate genes for pig growth curves

    Directory of Open Access Journals (Sweden)

    Fabyano Fonseca e Silva

    Full Text Available ABSTRACT: Genome association analyses have been successful in identifying quantitative trait loci (QTLs for pig body weights measured at a single age. However, when considering the whole weight trajectories over time in the context of genome association analyses, it is important to look at the markers that affect growth curve parameters. The easiest way to consider them is via the two-step method, in which the growth curve parameters and marker effects are estimated separately, thereby resulting in a reduction of the statistical power and the precision of estimates. One efficient solution is to adopt nonlinear mixed models (NMM, which enables a joint modeling of the individual growth curves and marker effects. Our aim was to propose a genome association analysis for growth curves in pigs based on NMM as well as to compare it with the traditional two-step method. In addition, we also aimed to identify the nearest candidate genes related to significant SNP (single nucleotide polymorphism markers. The NMM presented a higher number of significant SNPs for adult weight (A and maturity rate (K, and provided a direct way to test SNP significance simultaneously for both the A and K parameters. Furthermore, all significant SNPs from the two-step method were also reported in the NMM analysis. The ontology of the three candidate genes (SH3BGRL2, MAPK14, and MYL9 derived from significant SNPs (simultaneously affecting A and K allows us to make inferences with regards to their contribution to the pig growth process in the population studied.

  13. The association between alcohol use and problematic internet use: A large-scale nationwide cross-sectional study of adolescents in Japan.

    Science.gov (United States)

    Morioka, Hisayoshi; Itani, Osamu; Osaki, Yoneatsu; Higuchi, Susumu; Jike, Maki; Kaneita, Yoshitaka; Kanda, Hideyuki; Nakagome, Sachi; Ohida, Takashi

    2017-03-01

    This study aimed to clarify the associations between the frequency and amount of alcohol consumption and problematic Internet use, such as Internet addiction and excessive Internet use. A self-administered questionnaire survey was administered to students enrolled in randomly selected junior and senior high schools throughout Japan, and responses from 100,050 students (51,587 males and 48,463 females) were obtained. Multiple logistic regression analyses were performed in order to examine the associations between alcohol use and problematic Internet, use such as Internet addiction (Young Diagnostic Questionnaire for Internet Addiction ≥5) and excessive Internet use (≥5 h/day). The results of multiple logistic regression analyses indicated that the adjusted odds ratios for Internet addiction (YDQ ≥5) and excessive Internet use (≥5 h/day) became higher as the number of days in which alcohol had been consumed during the previous 30 days increased. In addition, the adjusted odds ratio for excessive Internet use (≥5 h/day) indicated a dose-dependent association with the amount of alcohol consumed per session. This study revealed that adolescents showing problematic Internet use consumed alcohol more frequently and consumed a greater amount of alcohol than those without problematic Internet use. These findings suggest a close association between drinking and problematic Internet use among Japanese adolescents. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. Religion and body weight: a review of quantitative studies.

    Science.gov (United States)

    Yeary, Karen Hye-Cheon Kim; Sobal, Jeffery; Wethington, Elaine

    2017-10-01

    Increasing interest in relationships between religion and health has encouraged research about religion and body weight, which has produced mixed findings. We systematically searched 11 bibliographic databases for quantitative studies of religion and weight, locating and coding 85 studies. We conducted a systematic review, analysing descriptive characteristics of the studies as well as relevant religion-body weight associations related to study characteristics. We summarized findings for two categories of religion variables: religious affiliation and religiosity. For religious affiliation, we found evidence for significant associations with body weight in both cross-sectional and longitudinal studies. In particular, Seventh-Day Adventists had lower body weight than other denominations in cross-sectional analyses. For religiosity, significant associations occurred between greater religiosity and higher body weight in both cross-sectional and longitudinal studies. In particular, greater religiosity was significantly associated with higher body weight in bivariate analyses but less so in multivariate analyses. A greater proportion of studies that used a representative sample, longitudinal analyses, and samples with only men reported significant associations between religiosity and weight. Evidence in seven studies suggested that health behaviours and psychosocial factors mediate religion-weight relationships. More longitudinal studies and analyses of mediators are needed to provide stronger evidence and further elucidate religion-weight relationships. © 2017 World Obesity Federation.

  15. A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia

    Science.gov (United States)

    Liu, Xiaoming; Yang, Jiasheng; Zhang, Yi; Fang, Yun; Wang, Fayou; Wang, Jun; Zheng, Xiaoqi; Yang, Jialiang

    2016-03-01

    We have studied drug-response associated (DRA) gene expressions by applying a systems biology framework to the Cancer Cell Line Encyclopedia data. More than 4,000 genes are inferred to be DRA for at least one drug, while the number of DRA genes for each drug varies dramatically from almost 0 to 1,226. Functional enrichment analysis shows that the DRA genes are significantly enriched in genes associated with cell cycle and plasma membrane. Moreover, there might be two patterns of DRA genes between genders. There are significantly shared DRA genes between male and female for most drugs, while very little DRA genes tend to be shared between the two genders for a few drugs targeting sex-specific cancers (e.g., PD-0332991 for breast cancer and ovarian cancer). Our analyses also show substantial difference for DRA genes between young and old samples, suggesting the necessity of considering the age effects for personalized medicine in cancers. Lastly, differential module and key driver analyses confirm cell cycle related modules as top differential ones for drug sensitivity. The analyses also reveal the role of TSPO, TP53, and many other immune or cell cycle related genes as important key drivers for DRA network modules. These key drivers provide new drug targets to improve the sensitivity of cancer therapy.

  16. No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects.

    Directory of Open Access Journals (Sweden)

    Jens Baumert

    Full Text Available Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI. Genome-wide association studies (GWAS have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

  17. The long-term association of OCD and depression and its moderators: A four-year follow up study in a large clinical sample.

    Science.gov (United States)

    Tibi, L; van Oppen, P; van Balkom, A J L M; Eikelenboom, M; Rickelt, J; Schruers, K R J; Anholt, G E

    2017-07-01

    Depression is the most common comorbidity in obsessive-compulsive disorder (OCD). However, the mechanisms of depressive comorbidity in OCD are poorly understood. We assessed the directionality and moderators of the OCD-depression association over time in a large, prospective clinical sample of OCD patients. Data were drawn from 382 OCD patients participating at the Netherlands Obsessive-Compulsive Disorder Association (NOCDA) study. Cross-lagged, structural equation modeling analyses were used to assess the temporal association between OCD and depressive symptoms. Assessments were conducted at baseline, two-year and four-year follow up. Cognitive and interpersonal moderators of the prospective association between OCD and depressive symptoms were tested. Cross-lagged analyses demonstrated that OCD predicts depressive symptoms at two-year follow up and not vice a versa. This relationship disappeared at four-year follow up. Secure attachment style moderated the prospective association between OCD and depression. Depressive comorbidity in OCD might constitute a functional consequence of the incapacitating OCD symptoms. Both OCD and depression symptoms demonstrated strong stability effects between two-year and four-year follow up, which may explain the lack of association between them in that period. Among OCD patients, secure attachment represents a buffer against future depressive symptoms. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Chemical and geotechnical analyses of soil samples from Olkiluoto for studies on sorption in soils

    International Nuclear Information System (INIS)

    Lusa, M.; Aemmaelae, K.; Hakanen, M.; Lehto, J.; Lahdenperae, A.-M.

    2009-05-01

    The safety assessment of disposal of spent nuclear fuel will include an estimate on the behavior of nuclear waste nuclides in the biosphere. As a part of this estimate also the transfer of nuclear waste nuclides in the soil and sediments is to be considered. In this study soil samples were collected from three excavator pits in Olkiluoto and the geotechnical and chemical characteristics of the samples were determined. In later stage these results will be used in sorption tests. Aim of these tests is to determine the Kd-values for Cs, Tc and I and later for Mo, Nb and Cl. Results of these sorption tests will be reported later. The geotechnical characteristics studied included dry weight and organic matter content as well as grain size distribution and mineralogy analyses. Selective extractions were carried out to study the sorption of cations into different mineral types. The extractions included five steps in which the cations bound to exchangeable, carbonate, oxides of Fe and Mn, organic matter and residual fractions were determined. For all fractions ICPMS analyses were carried out. In these analyses Li, Na, Mg, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Cs and Pb were determined. In addition six profiles were taken from the surroundings of two excavator pits for the 137 Cs determination. Besides the samples taken for the characterization of soil, supplement samples were taken from the same layers for the separation of soil water. From the soil water pH, DOC, anions (F, Cl, NO 3 , SO 4 ) and cations (Na, Mg, K, Ca, Al, Cr, Mn, Fe, Ni, Cu, Zn, As, S, Cd, Cs, Pb, U) were determined. (orig.)

  19. Association between intake of less-healthy foods defined by the United Kingdom's nutrient profile model and cardiovascular disease: A population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Oliver T Mytton

    2018-01-01

    Full Text Available In the United Kingdom, the Food Standards Agency-Ofcom nutrient profiling model (FSA-Ofcom model is used to define less-healthy foods that cannot be advertised to children. However, there has been limited investigation of whether less-healthy foods defined by this model are associated with prospective health outcomes. The objective of this study was to test whether consumption of less-healthy food as defined by the FSA-Ofcom model is associated with cardiovascular disease (CVD.We used data from the European Prospective Investigation of Cancer (EPIC-Norfolk cohort study in adults (n = 25,639 aged 40-79 years who completed a 7-day diet diary between 1993 and 1997. Incident CVD (primary outcome, cardiovascular mortality, and all-cause mortality (secondary outcomes were identified using record linkage to hospital admissions data and death certificates up to 31 March 2015. Each food and beverage item reported was coded and given a continuous score, using the FSA-Ofcom model, based on the consumption of energy; saturated fat; total sugar; sodium; nonsoluble fibre; protein; and fruits, vegetables, and nuts. Items were classified as less-healthy using Ofcom regulation thresholds. We used Cox proportional hazards regression to test for an association between consumption of less-healthy food and incident CVD. Sensitivity analyses explored whether the results differed based on the definition of the exposure. Analyses were adjusted for age, sex, behavioural risk factors, clinical risk factors, and socioeconomic status. Participants were followed up for a mean of 16.4 years. During follow-up, there were 4,965 incident cases of CVD (1,524 fatal within 30 days. In the unadjusted analyses, we observed an association between consumption of less-healthy food and incident CVD (test for linear trend over quintile groups, p < 0.01. After adjustment for covariates (sociodemographic, behavioural, and indices of cardiovascular risk, we found no association between

  20. The influence of familial factors on the intelligence-mortality association

    DEFF Research Database (Denmark)

    Christensen, G. T.; Osler, M.; Madsen, M.

    2017-01-01

    The aim was to investigate whether the widely reported inverse intelligence-mortality association could be replicated in twin intrapair analyses in which genetic and shared environmental factors are controlled for, as per the study design. Furthermore, the issue of generalizability of twin findings......-mortality associations were replicated in intrapair analyses of all twins and DZ twins where genetic and shared familial factors were partly controlled for, as per the study design. For twin pairs with a difference in intelligence test-score of half a standard deviation or more, the proportion of twin pairs in which...