WorldWideScience

Sample records for strongest associations identified

  1. Heart and/or soul : reality and fiction in the association between the two strongest contributors to the global burden of disease - ischemic heart disease and depression

    NARCIS (Netherlands)

    de Jonge, Peter

    Depression and heart disease are the strongest contributors to the global burden of disease and are often intertwined: depression is a risk factor for heart disease and vice versa. Moreover, depression in patients with established heart disease is associated with cardiovascular disease progression.

  2. Priorities for action on the social determinants of health: Empirical evidence on the strongest associations with life expectancy in 54 low-income countries, 1990-2012.

    Science.gov (United States)

    Hauck, K; Martin, S; Smith, P C

    2016-10-01

    The WHO Commission on the Social Determinants of Health set out an impressive collection of policy proposals on the social determinants of health. However, a serious weakness for securing implementation is the difficulty for policymakers in identifying priorities for action. The objective of this study is to determine a small set of the most influential determinants using existing data and an empirical approach. 45 Indicators from the World Bank's World Development Indicators are selected to measure attainment for the determinants proposed by the Commission. Panel data models of life expectancy at birth for 54 low-income countries over the years 1990-2012 (1188 country-years) are estimated. Each determinant is subjected to a robustness test using Extreme Bound Analysis, to determine the stability of its estimated impact on life expectancy. For 20 robust and significant determinants the magnitude of association with life expectancy is determined. The largest average increases in life expectancy at 14.5 months per capita is associated with a one standard deviation reduction in HIV prevalence among children, followed by advances in gender equality at 9.4 months. Improvements in life expectancy between 6 and 9 months are associated with agricultural production, political stability, access to clean water and sanitation, good governance, and primary school enrolment. Improvements below 6 months are associated with increases in private health expenditure and overseas development assistance, and control of armed conflict and HIV prevalence among men. There is no evidence that national income, public spending on healthcare and education, secondary schooling, terms of international trade, employment, debt service and relief, out-of-pocket expenditures, agricultural ex- or imports, lifestock production, foreign investment, urbanization or environmental degradation are robustly associated with population health. Results provide support for the relevance of some proposed

  3. Diabetes susceptibility in ethnic minority groups from Turkey, Vietnam, Sri Lanka and Pakistan compared with Norwegians - the association with adiposity is strongest for ethnic minority women

    Directory of Open Access Journals (Sweden)

    Jenum Anne

    2012-03-01

    Full Text Available Abstract Background The difference in diabetes susceptibility by ethnic background is poorly understood. The aim of this study was to assess the association between adiposity and diabetes in four ethnic minority groups compared with Norwegians, and take into account confounding by socioeconomic position. Methods Data from questionnaires, physical examinations and serum samples were analysed for 30-to 60-year-olds from population-based cross-sectional surveys of Norwegians and four immigrant groups, comprising 4110 subjects born in Norway (n = 1871, Turkey (n = 387, Vietnam (n = 553, Sri Lanka (n = 879 and Pakistan (n = 420. Known and screening-detected diabetes cases were identified. The adiposity measures BMI, waist circumference and waist-hip ratio (WHR were categorized into levels of adiposity. Gender-specific logistic regression models were applied to estimate the risk of diabetes for the ethnic minority groups adjusted for adiposity and income-generating work, years of education and body height used as a proxy for childhood socioeconomic position. Results The age standardized diabetes prevalence differed significantly between the ethnic groups (women/men: Pakistan: 26.4% (95% CI 20.1-32.7/20.0% (14.9-25.2; Sri Lanka: 22.5% (18.1-26.9/20.7% (17.3-24.2, Turkey: 11.9% (7.2-16.7/12.0% (7.6-16.4, Vietnam: 8.1% (5.1-11.2/10.4% (6.6-14.1 and Norway: 2.7% (1.8-3.7/6.4% (4.6-8.1. The prevalence increased more in the minority groups than in Norwegians with increasing levels of BMI, WHR and waist circumference, and most for women. Highly significant ethnic differences in the age-standardized prevalence of diabetes were found for both genders in all categories of all adiposity measures (p Conclusions A high prevalence of diabetes was found in 30-to 60-year-olds from ethnic minority groups in Oslo, with those from Sri Lanka and Pakistan at highest risk. For all levels of adiposity, a higher susceptibility for diabetes was observed for ethnic minority

  4. Diabetes susceptibility in ethnic minority groups from Turkey, Vietnam, Sri Lanka and Pakistan compared with Norwegians - the association with adiposity is strongest for ethnic minority women.

    Science.gov (United States)

    Jenum, Anne Karen; Diep, Lien My; Holmboe-Ottesen, Gerd; Holme, Ingar Morten K; Kumar, Bernadette Nirmar; Birkeland, Kåre Inge

    2012-03-01

    The difference in diabetes susceptibility by ethnic background is poorly understood. The aim of this study was to assess the association between adiposity and diabetes in four ethnic minority groups compared with Norwegians, and take into account confounding by socioeconomic position. Data from questionnaires, physical examinations and serum samples were analysed for 30-to 60-year-olds from population-based cross-sectional surveys of Norwegians and four immigrant groups, comprising 4110 subjects born in Norway (n = 1871), Turkey (n = 387), Vietnam (n = 553), Sri Lanka (n = 879) and Pakistan (n = 420). Known and screening-detected diabetes cases were identified. The adiposity measures BMI, waist circumference and waist-hip ratio (WHR) were categorized into levels of adiposity. Gender-specific logistic regression models were applied to estimate the risk of diabetes for the ethnic minority groups adjusted for adiposity and income-generating work, years of education and body height used as a proxy for childhood socioeconomic position. The age standardized diabetes prevalence differed significantly between the ethnic groups (women/men): Pakistan: 26.4% (95% CI 20.1-32.7)/20.0% (14.9-25.2); Sri Lanka: 22.5% (18.1-26.9)/20.7% (17.3-24.2), Turkey: 11.9% (7.2-16.7)/12.0% (7.6-16.4), Vietnam: 8.1% (5.1-11.2)/10.4% (6.6-14.1) and Norway: 2.7% (1.8-3.7)/6.4% (4.6-8.1). The prevalence increased more in the minority groups than in Norwegians with increasing levels of BMI, WHR and waist circumference, and most for women. Highly significant ethnic differences in the age-standardized prevalence of diabetes were found for both genders in all categories of all adiposity measures (p < 0.001). The Odds Ratio (OR) for diabetes adjusted for age, WHR, body height, education and income-generating work with Norwegians as reference was 2.9 (1.30-6.36) for Turkish, 2.7 (1.29-5.76) for Vietnamese, 8.0 (4.19-15.14) for Sri Lankan and 8.3 (4.37-15.58) for Pakistani women. Men from Sri Lanka and

  5. The strongest magnetic fields in the universe

    CERN Document Server

    Balogh, A; Falanga, M; Lyutikov, M; Mereghetti, S; Piran, T; Treumann, RA

    2016-01-01

    This volume extends the ISSI series on magnetic fields in the Universe into the domain of what are by far the strongest fields in the Universe, and stronger than any field that could be produced on Earth. The chapters describe the magnetic fields in non-degenerate strongly magnetized stars, degenerate stars (such as white dwarfs and neutron stars), exotic members called magnetars, and in their environments, as well as magnetic fields in the environments of black holes. These strong fields have a profound effect on the behavior of matter, visible in particular in highly variable processes like radiation in all known wavelengths, including Gamma-Ray bursts. The generation and structure of such strong magnetic fields and effects on the environment are also described.

  6. The Strongest Magnetic Field in Sunspots

    Science.gov (United States)

    Okamoto, J.; Sakurai, T.

    2017-12-01

    Sunspots are concentrations of magnetic fields on the solar surface. Generally, the strongest magnetic field in each sunspot is located in the dark umbra in most cases. A typical field strength in sunspots is around 3,000 G. On the other hand, some exceptions also have been found in complex sunspots with bright regions such as light bridges that separate opposite polarity umbrae, for instance with a strength of 4,300 G. However, the formation mechanism of such strong fields outside umbrae is still puzzling. Here we report an extremely strong magnetic field in a sunspot, which was located in a bright region sandwiched by two opposite-polarity umbrae. The strength is 6,250 G, which is the largest ever observed since the discovery of magnetic field on the Sun in 1908 by Hale. We obtained 31 scanned maps of the active region observed by Hinode/SOT/SP with a cadence of 3 hours over 5 days (February 1-6, 2014). Considering the spatial and temporal evolution of the vector magnetic field and the Doppler velocity in the bright region, we suggested that this strong field region was generated as a result of compression of one umbra pushed by the outward flow from the other umbra (Evershed flow), like the subduction of the Earth's crust in plate tectonics.

  7. Congenital Heart Diseases associated with Identified Syndromes ...

    African Journals Online (AJOL)

    Recognised syndromes were seen in 69(68%) cases. Down syndrome with 54 children contributed 78.3% of those with known syndromes. Other identified syndromes and associations were Marfan's, Noonan's, Edwards, Prune Belly, Apert, Ellis-van creveld syndrome and congenital rubella syndrome. Congenital heart ...

  8. Genome-wide Linkage and Association Analyses to Identify Genes Influencing Adiponectin Levels: The GEMS Study

    Science.gov (United States)

    Ling, Hua; Waterworth, Dawn M.; Stirnadel, Heide A.; Pollin, Toni I.; Barter, Philip J.; Kesäniemi, Y. Antero; Mahley, Robert W.; McPherson, Ruth; Waeber, Gérard; Bersot, Thomas P.; Cohen, Jonathan C.; Grundy, Scott M.; Mooser, Vincent E.; Mitchell, Braxton D.

    2014-01-01

    Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K Affymetrix platform) was carried out in a set of unrelated NWE subjects consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight subjects with normal lipids. Peak evidence for linkage occurred at chromosome 8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis, the single-nucleotide polymorphisms (SNPs) most strongly associated with adiponectin were rs3774261 and rs6773957 (P < 10−7). These two SNPs were in high linkage disequilibrium (r2 = 0.98) and located within ADIPOQ. Interestingly, our fourth strongest region of association (P < 2 × 10−5) was to an SNP within CDH13, whose protein product is a newly identified receptor for high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed previous studies showing SNPs within ADIPOQ to be strongly associated with variation in adiponectin levels and further observed these to have the strongest effects on adiponectin levels throughout the genome. We additionally identified a second gene (CDH13) possibly influencing variation in adiponectin levels. The impact of these SNPs on health and disease has yet to be determined. PMID:19165155

  9. Phenome-wide scanning identifies multiple diseases and disease severity phenotypes associated with HLA variants.

    Science.gov (United States)

    Karnes, Jason H; Bastarache, Lisa; Shaffer, Christian M; Gaudieri, Silvana; Xu, Yaomin; Glazer, Andrew M; Mosley, Jonathan D; Zhao, Shilin; Raychaudhuri, Soumya; Mallal, Simon; Ye, Zhan; Mayer, John G; Brilliant, Murray H; Hebbring, Scott J; Roden, Dan M; Phillips, Elizabeth J; Denny, Joshua C

    2017-05-10

    Although many phenotypes have been associated with variants in human leukocyte antigen (HLA) genes, the full phenotypic impact of HLA variants across all diseases is unknown. We imputed HLA genomic variation from two populations of 28,839 and 8431 European ancestry individuals and tested association of HLA variation with 1368 phenotypes. A total of 104 four-digit and 92 two-digit HLA allele phenotype associations were significant in both discovery and replication cohorts, the strongest being HLA-DQB1*03:02 and type 1 diabetes. Four previously unidentified associations were identified across the spectrum of disease with two- and four-digit HLA alleles and 10 with nonsynonymous variants. Some conditions associated with multiple HLA variants and stronger associations with more severe disease manifestations were identified. A comprehensive, publicly available catalog of clinical phenotypes associated with HLA variation is provided. Examining HLA variant disease associations in this large data set allows comprehensive definition of disease associations to drive further mechanistic insights. Copyright © 2017, American Association for the Advancement of Science.

  10. A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis.

    Science.gov (United States)

    Saxena, Richa; Plenge, Robert M; Bjonnes, Andrew C; Dashti, Hassan S; Okada, Yukinori; Gad El Haq, Wessam; Hammoudeh, Mohammed; Al Emadi, Samar; Masri, Basel K; Halabi, Hussein; Badsha, Humeira; Uthman, Imad W; Margolin, Lauren; Gupta, Namrata; Mahfoud, Ziyad R; Kapiri, Marianthi; Dargham, Soha R; Aranki, Grace; Kazkaz, Layla A; Arayssi, Thurayya

    2017-05-01

    Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome-wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab-specific genetic loci. The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single-nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population. Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome-wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA-DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10 -16 ), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10 -5 ) and with seropositive RA (P = 1.48 × 10 -6 ) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci. This first RA GWAS in Arab populations confirms that established HLA-region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population-specific insights into the

  11. Caregiver burden: the strongest predictor of self-rated health in caregivers of patients with dementia.

    Science.gov (United States)

    Abdollahpour, Ibrahim; Nedjat, Saharnaz; Noroozian, Maryam; Salimi, Yahya; Majdzadeh, Reza

    2014-09-01

    People having dementia need help and supervision to perform their activities of daily living. This responsibility is usually imposed on family members who endure a great burden, leading to undesirable health outcomes. The aims of our study were to measure caregivers' health as well as identify its adjusted relevant predictors. One hundred and fifty three registered patients and their caregivers from Iranian Alzheimer Association were included in this cross-sectional study through sequential sampling. Self-rated health (SRH) was measured using a single question with Likert-type scale ranging from very bad (1) to very good (5). The multiple linear regression model was applied to determine the adjusted associations between independent variables under study and SRH. The mean caregiver SRH level was 3.03. Of the participant caregivers, 29% were either unsatisfied or very unsatisfied with their health level. In the final regression model, SRH showed a direct significant association with the patient's number of children but an inverse significant association with the marital status (married patients), patient's age, and caregiver burden. Caregiver burden was not only significantly associated with poor SRH after removing the effect of the other covariates but it was also recognized as the strongest predictor of caregivers' SRH. Therefore, it seems that development of intervention programs, in order to reduce caregiver burden, can be considered as important step in promoting caregivers' health level. © The Author(s) 2014.

  12. Genome-wide association study identifies five new schizophrenia loci.

    LENUS (Irish Health Repository)

    Ripke, Stephan

    2011-10-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

  13. Salomon: '97 E and P looking strongest in 9 years

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    Based on companies' disclosed spending plans, 1997 is shaping up to be the strongest year-ahead outlook in 9 years, according to Salomon Bros. Inc. Salomon Bros.' conclusion stems from its 15th annual survey of worldwide oil and gas exploration and production spending. The survey, released last month, included 125 US independents, 97 Canadian companies, 103 companies outside the US and Canada, and 15 majors. Significantly, when the 15% growth experienced in 1996 is combined with the 1997 outlook, it represents the strongest indicator of 2-year activity in the past 15 years, said Salomon Bros. Double-digit spending growth is projected in all regions for 1997, the analyst said. Salomon Bros. said a higher percentage of companies' E and P budgets are being allocated to offshore projects, driven in part by attractive prospects, 3D seismic technology, and increased operational efficiencies

  14. Data Mining for Identifying Novel Associations and Temporal Relationships with Charcot Foot

    Directory of Open Access Journals (Sweden)

    Michael E. Munson

    2014-01-01

    Full Text Available Introduction. Charcot foot is a rare and devastating complication of diabetes. While some risk factors are known, debate continues regarding etiology. Elucidating other associated disorders and their temporal occurrence could lead to a better understanding of its pathogenesis. We applied a large data mining approach to Charcot foot for elucidating novel associations. Methods. We conducted an association analysis using ICD-9 diagnosis codes for every patient in our health system (n=1.6 million with 41.2 million time-stamped ICD-9 codes. For the current analysis, we focused on the 388 patients with Charcot foot (ICD-9 713.5. Results. We found 710 associations, 676 (95.2% of which had a P value for the association less than 1.0×10−5 and 603 (84.9% of which had an odds ratio > 5.0. There were 111 (15.6% associations with a significant temporal relationship P<1.0×10−3. The three novel associations with the strongest temporal component were cardiac dysrhythmia, pulmonary eosinophilia, and volume depletion disorder. Conclusion. We identified novel associations with Charcot foot in the context of pathogenesis models that include neurotrophic, neurovascular, and microtraumatic factors mediated through inflammatory cytokines. Future work should focus on confirmatory analyses. These novel areas of investigation could lead to prevention or earlier diagnosis.

  15. 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.

  16. Considering body mass differences, who are the world's strongest women?

    Science.gov (United States)

    Vanderburgh, P M; Dooman, C

    2000-01-01

    Allometric modeling (AM) has been used to determine the world's strongest body mass-adjusted man. Recently, however, AM was shown to demonstrate body mass bias in elite Olympic weightlifting performance. A second order polynomial (2OP) provided a better fit than AM with no body mass bias for men and women. The purpose of this study was to apply both AM and 2OP models to women's world powerlifting records (more a function of pure strength and less power than Olympic lifts) to determine the optimal model approach as well as the strongest body mass-adjusted woman in each event. Subjects were the 36 (9 per event) current women world record holders (as of Nov., 1997) for bench press (BP), deadlift (DL), squat (SQ), and total (TOT) lift (BP + DL + SQ) according to the International Powerlifting Federation (IPF). The 2OP model demonstrated the superior fit and no body mass bias as indicated by the coefficient of variation and residuals scatterplot inspection, respectively, for DL, SQ, and TOT. The AM for these three lifts, however, showed favorable bias toward the middle weight classes. The 2OP and AM yielded an essentially identical fit for BP. Although body mass-adjusted world records were dependent on the model used, Carrie Boudreau (U.S., 56-kg weight class), who received top scores in TOT and DL with both models, is arguably the world's strongest woman overall. Furthermore, although the 2OP model provides a better fit than AM for this elite population, a case can still be made for AM use, particularly in light of theoretical superiority.

  17. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing ...

  18. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  19. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Murabito, Joanne M; White, Charles C; Kavousi, Maryam

    2012-01-01

    meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (ß= -0.006, p=2.46x10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined...... discovery and replication analysis (p=2.65x10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI: DAB21P (rs13290547, p=3.6x10(-5)); CYBA...... (rs3794624, p=6.3x10(-5)); and rs1122608 (LDLR, p=0.0026). CONCLUSIONS: -GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI....

  20. The Strength of the Strongest Ties in Collaborative Problem Solving

    DEFF Research Database (Denmark)

    de Montjoye, Yves-Alexandre; Stopczynski, Arkadiusz; Shmueli, Erez

    2014-01-01

    Complex problem solving in science, engineering, and business has become a highly collaborative endeavor. Teams of scientists or engineers collaborate on projects using their social networks to gather new ideas and feedback. Here we bridge the literature on team performance and information networks...... by studying teams' problem solving abilities as a function of both their within-team networks and their members' extended networks. We show that, while an assigned team's performance is strongly correlated with its networks of expressive and instrumental ties, only the strongest ties in both networks have......-significant in the statistical analysis. Our results have consequences for the organization of teams of scientists, engineers, and other knowledge workers tackling today's most complex problems....

  1. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

    Directory of Open Access Journals (Sweden)

    Fuu-Jen Tsai

    2010-02-01

    Full Text Available To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D in a Han Chinese population. A two-stage genome-wide association (GWA study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD (P = 8.54x10(-10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82, and serine racemase (SRR (P = 3.06x10(-9; OR = 1.28; 95% CI = 1.18-1.39. We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10; OR = 1.29, 95% CI = 1.19-1.40. By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

  2. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  3. A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Tyrer, Jonathan

    2009-01-01

    ,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P ... (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest...

  4. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz

    2016-01-01

    power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from......Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...

  5. Pathway analysis of bladder cancer genome-wide association study identifies novel pathways involved in bladder cancer development.

    Science.gov (United States)

    Chen, Meng; Rothman, Nathaniel; Ye, Yuanqing; Gu, Jian; Scheet, Paul A; Huang, Maosheng; Chang, David W; Dinney, Colin P; Silverman, Debra T; Figueroa, Jonine D; Chanock, Stephen J; Wu, Xifeng

    2016-07-01

    Genome-wide association studies (GWAS) are designed to identify individual regions associated with cancer risk, but only explain a small fraction of the inherited variability. Alternative approach analyzing genetic variants within biological pathways has been proposed to discover networks of susceptibility genes with additional effects. The gene set enrichment analysis (GSEA) may complement and expand traditional GWAS analysis to identify novel genes and pathways associated with bladder cancer risk. We selected three GSEA methods: Gen-Gen, Aligator, and the SNP Ratio Test to evaluate cellular signaling pathways involved in bladder cancer susceptibility in a Texas GWAS population. The candidate genetic polymorphisms from the significant pathway selected by GSEA were validated in an independent NCI GWAS. We identified 18 novel pathways ( P CACNA1S, COL4A2, SRC , and CACNA1C were associated with bladder cancer risk. Two CCNE1 variants, rs8102137 and rs997669, from cell cycle pathways showed the strongest associations; the CCNE1 signal at 19q12 has already been reported in previous GWAS. These findings offer additional etiologic insights highlighting the specific genes and pathways associated with bladder cancer development. GSEA may be a complementary tool to GWAS to identify additional loci of cancer susceptibility.

  6. Association analysis identifies 65 new breast cancer risk loci

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe

    2017-01-01

    cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P risk single-nucleotide polymorphisms in these loci fall......Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast......-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores...

  7. Identifying Factors Associated With Mobility Decline Among Hospitalized Older Adults.

    Science.gov (United States)

    Chase, Jo-Ana D; Lozano, Alicia; Hanlon, Alexandra; Bowles, Kathryn H

    2018-02-01

    Hospitalization can negatively affect mobility among older adults. Early detection of older patients most at risk for mobility decline can lead to early intervention and prevention of mobility loss. This study's purpose was to identify factors from the International Classification of Functioning, Disability, and Health associated with mobility decline among hospitalized elders. We conducted a secondary analysis of data from 959 hospitalized adults age 65 and older. We estimated the effects of health conditions and environmental and personal factors on mobility decline using logistic regression. Almost half of the sample declined in mobility function during hospitalization. Younger age, longer length of hospital stay, having a hearing impairment, and non-emergency admit type were associated with mobility decline, after adjusting for covariates. Findings may be used to develop an evidence-based, risk-determination tool for hospitalized elders. Future research should focus on individual, environmental, and policy-based interventions promoting physical activity in the hospital.

  8. Identifying and mitigating risks for agricultural injury associated with obesity

    Directory of Open Access Journals (Sweden)

    Nathan King

    2016-12-01

    Full Text Available In some occupational contexts overweight and obesity have been identified as risk factors for injury. The purpose of this study was to examine this hypothesis within farm work environments and then to identify specific opportunities for environmental modification as a preventive strategy. Data on farm-related injuries, height and weight used to calculate body mass index (BMI, and demographic characteristics were from the Phase 2 baseline survey of the Saskatchewan Farm Injury Cohort; a large cross-sectional mail-based survey conducted in Saskatchewan, Canada from January through May 2013. Multivariable logistic regression was used to examine associations between BMI and injury. Injury narratives were explored qualitatively. Findings were inconsistent and differed according to gender. Among women (n = 927, having overweight (adjusted OR: 2.94; 95% CI: 1.29 to 6.70 but not obesity (1.10; 95% CI: 0.35 to 3.43 was associated with an increased odds of incurring a farm-related injury. No strong or statistically significant effects were observed for men (n = 1406 with overweight or obesity. While injury-related challenges associated with obesity have been addressed in other occupational settings via modification of the worksite, such strategies are challenging to implement in farm settings because of the diversity of work tasks and associated hazards. We conclude that the acute effects of overweight in terms of injury do require consideration in agricultural populations, but these should also be viewed with a differentiation based on gender.

  9. Genome wide association identifies novel loci involved in fungal communication.

    Science.gov (United States)

    Palma-Guerrero, Javier; Hall, Charles R; Kowbel, David; Welch, Juliet; Taylor, John W; Brem, Rachel B; Glass, N Louise

    2013-01-01

    Understanding how genomes encode complex cellular and organismal behaviors has become the outstanding challenge of modern genetics. Unlike classical screening methods, analysis of genetic variation that occurs naturally in wild populations can enable rapid, genome-scale mapping of genotype to phenotype with a medium-throughput experimental design. Here we describe the results of the first genome-wide association study (GWAS) used to identify novel loci underlying trait variation in a microbial eukaryote, harnessing wild isolates of the filamentous fungus Neurospora crassa. We genotyped each of a population of wild Louisiana strains at 1 million genetic loci genome-wide, and we used these genotypes to map genetic determinants of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion, and we subjected these trait measurements to GWAS. This analysis identified one gene, NCU04379 (cse-1, encoding a homolog of a neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly impaired germling communication and fusion, and two genes encoding predicted interaction partners of CSE1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more previously unknown molecular players, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. Our results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power

  10. Levothyroxine therapy and impaired clearance are the strongest contributors to small intestinal bacterial overgrowth: Results of a retrospective cohort study.

    Science.gov (United States)

    Brechmann, Thorsten; Sperlbaum, Andre; Schmiegel, Wolff

    2017-02-07

    To identify a set of contributors, and weight and rank them on a pathophysiological basis. Patients who have undergone a lactulose or glucose hydrogen breath test to rule out small intestinal bacterial overgrowth (SIBO) for various clinical symptoms, including diarrhoea, weight loss, abdominal pain, cramping or bloating, were seen as eligible for inclusion in a retrospective single-centre study. Clinical data such as co-morbidities, medication, laboratory parameters and other possible risk factors have been identified from the electronic data system. Cases lacking or with substantially incomplete clinical data were excluded from the analysis. Suspected contributors were summarised under four different pathophysiological pathways (impaired gastric acid barrier, impaired intestinal clearance, immunosuppression and miscellaneous factors including thyroid gland variables) and investigated using the χ 2 test, Student's t -test and logistic regression models. A total of 1809 patients who had undergone hydrogen breath testing were analysed. Impairment of the gastric acid barrier (gastrectomy, odds ratio: OR = 3.5, PPI therapy OR = 1.4), impairment of intestinal clearance (any resecting gastric surgery OR = 2.6, any colonic resection OR = 1.9, stenosis OR = 3.4, gastroparesis OR = 3.4, neuropathy 2.2), immunological factors (any drug-induced immunosuppression OR = 1.8), altered thyroid gland metabolism (hypothyroidism OR = 2.6, levothyroxine therapy OR = 3.0) and diabetes mellitus (OR = 1.9) were associated significantly to SIBO. Any abdominal surgery, ileocecal resection, vagotomy or IgA-deficiency did not have any influence, and a history of appendectomy decreased the risk of SIBO. Multivariate analysis revealed gastric surgery, stenoses, medical immunosuppression and levothyroxine to be the strongest predictors. Levothyroxine therapy was the strongest contributor in a simplified model (OR = 3.0). The most important contributors for the development of SIBO in ascending

  11. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing......*0602. We found association with a protective variant near HLA-DQA2 (rs2858884; P ... ratio = 0.02; P HLA haplotype suggests a virtually causal involvement of the HLA region in narcolepsy susceptibility....

  12. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

    Science.gov (United States)

    Malta, Tathiane M; Sokolov, Artem; Gentles, Andrew J; Burzykowski, Tomasz; Poisson, Laila; Weinstein, John N; Kamińska, Bożena; Huelsken, Joerg; Omberg, Larsson; Gevaert, Olivier; Colaprico, Antonio; Czerwińska, Patrycja; Mazurek, Sylwia; Mishra, Lopa; Heyn, Holger; Krasnitz, Alex; Godwin, Andrew K; Lazar, Alexander J; Stuart, Joshua M; Hoadley, Katherine A; Laird, Peter W; Noushmehr, Houtan; Wiznerowicz, Maciej

    2018-04-05

    Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A genome wide association study of alcohol dependence symptom counts in extended pedigrees identifies C15orf53

    Science.gov (United States)

    Wang, Jen-Chyong; Foroud, Tatiana; Hinrichs, Anthony L; Le, Nhung XH; Bertelsen, Sarah; Budde, John P; Harari, Oscar; Koller, Daniel L; Wetherill, Leah; Agrawal, Arpana; Almasy, Laura; Brooks, Andrew I; Bucholz, Kathleen; Dick, Danielle; Hesselbrock, Victor; Johnson, Eric O; Kang, Sun; Kapoor, Manav; Kramer, John; Kuperman, Samuel; Madden, Pamela AF; Manz, Niklas; Martin, Nicholas G; McClintick, Jeanette N; Montgomery, Grant W; Nurnberger, John I; Rangaswamy, Madhavi; Rice, John; Schuckit, Marc; Tischfield, Jay A; Whitfield, John B; Xuei, Xiaoling; Porjesz, Bernice; Heath, Andrew C; Edenberg, Howard J; Bierut, Laura J; Goate, Alison M

    2013-01-01

    Several studies have identified genes associated with alcohol use disorders, but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism (COGA) to identify novel genes affecting risk for alcohol dependence. To maximize the power of the extended family design we used a quantitative endophenotype, measured in all individuals: number of alcohol dependence symptoms endorsed (symptom count). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with symptom count were also associated with the dichotomous phenotype, DSM-IV alcohol dependence. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol (p=4.5×10−8, inflation corrected p=9.4×10−7). Results with DSM-IV alcohol dependence in the regions of interest support our findings with symptom count, though the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: non-overlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian twin-family study of alcohol use disorders (OZALC). Nominal association of C15orf53 with symptom count was observed in SAGE. The variant that showed strongest association with symptom count, rs12912251 and its highly correlated variants (D′=1, r2≥ 0.95), has previously been associated with risk for bipolar disorder. PMID:23089632

  14. A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53.

    Science.gov (United States)

    Wang, J-C; Foroud, T; Hinrichs, A L; Le, N X H; Bertelsen, S; Budde, J P; Harari, O; Koller, D L; Wetherill, L; Agrawal, A; Almasy, L; Brooks, A I; Bucholz, K; Dick, D; Hesselbrock, V; Johnson, E O; Kang, S; Kapoor, M; Kramer, J; Kuperman, S; Madden, P A F; Manz, N; Martin, N G; McClintick, J N; Montgomery, G W; Nurnberger, J I; Rangaswamy, M; Rice, J; Schuckit, M; Tischfield, J A; Whitfield, J B; Xuei, X; Porjesz, B; Heath, A C; Edenberg, H J; Bierut, L J; Goate, A M

    2013-11-01

    Several studies have identified genes associated with alcohol-use disorders (AUDs), but the variation in each of these genes explains only a small portion of the genetic vulnerability. The goal of the present study was to perform a genome-wide association study (GWAS) in extended families from the Collaborative Study on the Genetics of Alcoholism to identify novel genes affecting risk for alcohol dependence (AD). To maximize the power of the extended family design, we used a quantitative endophenotype, measured in all individuals: number of alcohol-dependence symptoms endorsed (symptom count (SC)). Secondary analyses were performed to determine if the single nucleotide polymorphisms (SNPs) associated with SC were also associated with the dichotomous phenotype, DSM-IV AD. This family-based GWAS identified SNPs in C15orf53 that are strongly associated with DSM-IV alcohol-dependence symptom counts (P=4.5 × 10(-8), inflation-corrected P=9.4 × 10(-7)). Results with DSM-IV AD in the regions of interest support our findings with SC, although the associations were less significant. Attempted replications of the most promising association results were conducted in two independent samples: nonoverlapping subjects from the Study of Addiction: Genes and Environment (SAGE) and the Australian Twin Family Study of AUDs (OZALC). Nominal association of C15orf53 with SC was observed in SAGE. The variant that showed strongest association with SC, rs12912251 and its highly correlated variants (D'=1, r(2) 0.95), have previously been associated with risk for bipolar disorder.

  15. Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy

    DEFF Research Database (Denmark)

    Feenstra, Bjarke; Bager, Peter; Liu, Xueping

    2017-01-01

    BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associate...... the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system.......BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associated...... with tonsillectomy. METHODS: We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls. RESULTS...

  16. Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association between Seronegative Disease and Fibromyalgia

    Science.gov (United States)

    Doss, Jayanth; Mo, Huan; Carroll, Robert J.; Crofford, Leslie J.; Denny, Joshua C.

    2016-01-01

    Objective The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA. Methods A validated algorithm identified RA subjects from the de-identified EHR. Serotypes were determined by values of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA). We tested EHR-derived phenotypes using PheWAS comparing seropositive RA against seronegative RA, yielding disease associations. PheWAS was also performed on RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed and fibromyalgia was specifically evaluated using a validated algorithm. Results There were 2199 individuals identified with RA and either RF or ACPA testing. Of these, 1382 (63%) were seropositive. Seronegative RA was associated with “Myalgia and Myositis” (odds ratio [OR] 2.1, P=3.7×10−10) and back pain. A manual record review showed 80% of Myalgia and Myositis codes were used for fibromyalgia, and follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR=1.8, P=4.0×10−6). Seropositive RA was associated with Chronic Airway Obstruction (OR=2.2, P=1.4×10−4) and tobacco use (OR=2.2, P=7.0×10−4). Conclusion This PheWAS in RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity with chronic airway obstruction and seropositivity with tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. PMID:27589350

  17. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

    Science.gov (United States)

    de Boer, Ynto S; van Gerven, Nicole M F; Zwiers, Antonie; Verwer, Bart J; van Hoek, Bart; van Erpecum, Karel J; Beuers, Ulrich; van Buuren, Henk R; Drenth, Joost P H; den Ouden, Jannie W; Verdonk, Robert C; Koek, Ger H; Brouwer, Johannes T; Guichelaar, Maureen M J; Vrolijk, Jan M; Kraal, Georg; Mulder, Chris J J; van Nieuwkerk, Carin M J; Fischer, Janett; Berg, Thomas; Stickel, Felix; Sarrazin, Christoph; Schramm, Christoph; Lohse, Ansgar W; Weiler-Normann, Christina; Lerch, Markus M; Nauck, Matthias; Völzke, Henry; Homuth, Georg; Bloemena, Elisabeth; Verspaget, Hein W; Kumar, Vinod; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude; Bouma, Gerd

    2014-08-01

    Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus

    Science.gov (United States)

    Chen, Dan; Enroth, Stefan; Liu, Han; Sun, Yang; Wang, Huibo; Yu, Min; Deng, Lian; Xu, Shuhua; Gyllensten, Ulf

    2016-01-01

    Recent genome-wide association studies (GWASs) in subjects of European descent have identified associations between cervical cancer risk and three independent loci as well as multiple classical human leukocyte antigen (HLA) alleles at 6p21.3. To search for novel loci associated with development of cervical cancer, we performed a pooled analysis of data from two GWASs by imputing over 10 million genetic variants and 424 classical HLA alleles, for 1,553 intraepithelial neoplasia 3 (CIN3), 81 cervical cancer and 4,442 controls from the Swedish population. Notable findings were validated in an independent study of 961 patients (827 with CIN3 and 123 with cervical cancer) and 1,725 controls. Our data provided increased support for previously identified loci at 6p21.3 (rs9271898, P = 1.2 × 10−24; rs2516448, 1.1 × 10−15; and rs3130196, 2.3 × 10−9, respectively) and also confirmed associations with reported classical HLA alleles including HLA-B*07:02, -B*15:01, -DRB1*13:01, -DRB1*15:01, -DQA1*01:03, -DQB1*06:03 and -DQB1*06:02. In addition, we identified and subsequently replicated an independent signal at rs73730372 at 6p21.3 (odds ratio = 0.60, 95% confidence interval = 0.54–0.67, P = 3.0 × 10−19), which was found to be an expression quantitative trait locus (eQTL) of both HLA-DQA1 and HLA-DQB1. This is one of the strongest common genetic protective variants identified so far for CIN3. We also found HLA-C*07:02 to be associated with risk of CIN3. The present study provides new insights into pathogenesis of CIN3. PMID:27285765

  19. 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; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D'Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Mateo Leach, Irene; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    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

  20. Identifying relevant feature-action associations for grasping unmodelled objects

    DEFF Research Database (Denmark)

    Thomsen, Mikkel Tang; Kraft, Dirk; Krüger, Norbert

    2015-01-01

    content. The method is provided with a large and structured set of visual features, motivated by the visual hierarchy in primates and finds relevant feature action associations automatically. We apply our method in a simulated environment on three different object sets for the case of grasp affordance...

  1. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; Clair, David St.; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H. R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; De Hert, Marc; Jonsson, Erik G.; Bitter, Istvan; Pietilainen, Olli P. H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E.; Black, Donald W.; Borglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A.; Datta, Susmita; De Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthoj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Hultman, Christina M.; Ingason, Andres; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Juergens, Gesche; Kahn, Renes; Keller, Matthew C.; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K.; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F. Bernard; Liang, Kung-Yee; Lichtenstein, Paul; Lieberman, Jeffrey A.; Linszen, Don H.; Lonnqvist, Jouko; Loughland, Carmel M.; Maclean, Alan W.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A.; McGrath, John J.; McIntosh, Andrew; McLean, Duncan E.; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T.; Milanova, Vihra; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Noethen, Markus M.; O'Dushlaine, Colm T.; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Orntoft, Torben F.; Owen, Michael J.; Pantelis, Christos; Papadimitriou, George; Pato, Michele T.; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Quinn, Emma M.; Rasmussen, Henrik B.; Rethelyi, Janos M.; Ribble, Robert; Rietschel, Marcella; Riley, Brien P.; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scott, Rodney J.; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M.; Spencer, Chris C. A.; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H.; Timm, Sally; Toncheva, Draga; van den Oord, Edwin; van Os, Jim; van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G.; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F.; O'Donovan, Michael C.; Daly, Mark J.; Gejman, Pablo V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  2. Identifying factors associated with the discharge of male State ...

    African Journals Online (AJOL)

    Background: Designated psychiatric facilities are responsible for the care, treatment and reintegration of State patients. ... State patients were associated with being a primary caregiver (p = 0.031) having good insight into illness (p = 0.025) or offence (p = 0.005) and having had multiple successful leaves of absences.

  3. Association analysis identifies 65 new breast cancer risk loci

    NARCIS (Netherlands)

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe; Beesley, Jonathan; Hui, Shirley; Kar, Siddhartha; Lemaçon, Audrey; Soucy, Penny; Glubb, Dylan; Rostamianfar, Asha; Bolla, Manjeet K.; Wang, Qin; Tyrer, Jonathan; Dicks, Ed; Lee, Andrew; Wang, Zhaoming; Allen, Jamie; Keeman, Renske; Eilber, Ursula; French, Juliet D.; Qing Chen, Xiao; Fachal, Laura; McCue, Karen; McCart Reed, Amy E.; Ghoussaini, Maya; Carroll, Jason S.; Jiang, Xia; Finucane, Hilary; Adams, Marcia; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Arun, Banu; Auer, Paul L.; Bacot, François; Barrdahl, Myrto; Baynes, Caroline; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brand, Judith S.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Brinton, Louise; Broberg, Per; Brock, Ian W.; Broeks, Annegien; Brooks-Wilson, Angela; Brucker, Sara Y.; Brüning, Thomas; Burwinkel, Barbara; Butterbach, Katja; Cai, Qiuyin; Cai, Hui; Caldés, Trinidad; Canzian, Federico; Carracedo, Angel; Carter, Brian D.; Castelao, Jose E.; Chan, Tsun L.; David Cheng, Ting-Yuan; Seng Chia, Kee; Choi, Ji-Yeob; Christiansen, Hans; Clarke, Christine L.; Collée, Margriet; Conroy, Don M.; Cordina-Duverger, Emilie; Cornelissen, Sten; Cox, David G.; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Devilee, Peter; Doheny, Kimberly F.; Dörk, Thilo; Dos-Santos-Silva, Isabel; Dumont, Martine; Durcan, Lorraine; Dwek, Miriam; Eccles, Diana M.; Ekici, Arif B.; Eliassen, A. Heather; Ellberg, Carolina; Elvira, Mingajeva; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fritschi, Lin; Gaborieau, Valerie; Gabrielson, Marike; Gago-Dominguez, Manuela; Gao, Yu-Tang; Gapstur, Susan M.; García-Sáenz, José A.; Gaudet, Mia M.; Georgoulias, Vassilios; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Grenaker Alnæs, Grethe I.; Grip, Mervi; Gronwald, Jacek; Grundy, Anne; Guénel, Pascal; Haeberle, Lothar; Hahnen, Eric; Haiman, Christopher A.; Håkansson, Niclas; Hamann, Ute; Hamel, Nathalie; Hankinson, Susan; Harrington, Patricia; Hart, Steven N.; Hartikainen, Jaana M.; Hartman, Mikael; Hein, Alexander; Heyworth, Jane; Hicks, Belynda; Hillemanns, Peter; Ho, Dona N.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Hou, Ming-Feng; Hsiung, Chia-Ni; Huang, Guanmengqian; Humphreys, Keith; Ishiguro, Junko; Ito, Hidemi; Iwasaki, Motoki; Iwata, Hiroji; Jakubowska, Anna; Janni, Wolfgang; John, Esther M.; Johnson, Nichola; Jones, Kristine; Jones, Michael; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kaczmarek, Katarzyna; Kang, Daehee; Kasuga, Yoshio; Kerin, Michael J.; Khan, Sofia; Khusnutdinova, Elza; Kiiski, Johanna I.; Kim, Sung-Won; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela N.; Krüger, Ute; Kwong, Ava; Lambrechts, Diether; Le Marchand, Loic; Lee, Eunjung; Lee, Min Hyuk; Lee, Jong Won; Neng Lee, Chuen; Lejbkowicz, Flavio; Li, Jingmei; Lilyquist, Jenna; Lindblom, Annika; Lissowska, Jolanta; Lo, Wing-Yee; Loibl, Sibylle; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Luccarini, Craig; Lux, Michael P.; Ma, Edmond S. K.; MacInnis, Robert J.; Maishman, Tom; Makalic, Enes; Malone, Kathleen E.; Kostovska, Ivana Maleva; Mannermaa, Arto; Manoukian, Siranoush; Manson, JoAnn E.; Margolin, Sara; Mariapun, Shivaani; Martinez, Maria Elena; Matsuo, Keitaro; Mavroudis, Dimitrios; McKay, James; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Menéndez, Primitiva; Menon, Usha; Meyer, Jeffery; Miao, Hui; Miller, Nicola; Taib, Nur Aishah Mohd; Muir, Kenneth; Mulligan, Anna Marie; Mulot, Claire; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F.; Noh, Dong-Young; Nordestgaard, Børge G.; Norman, Aaron; Olopade, Olufunmilayo I.; Olson, Janet E.; Olsson, Håkan; Olswold, Curtis; Orr, Nick; Pankratz, V. Shane; Park, Sue K.; Park-Simon, Tjoung-Won; Lloyd, Rachel; Perez, Jose I. A.; Peterlongo, Paolo; Peto, Julian; Phillips, Kelly-Anne; Pinchev, Mila; Plaseska-Karanfilska, Dijana; Prentice, Ross; Presneau, Nadege; Prokofyeva, Darya; Pugh, Elizabeth; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rahman, Nazneen; Rennert, Gadi; Rennert, Hedy S.; Rhenius, Valerie; Romero, Atocha; Romm, Jane; Ruddy, Kathryn J.; Rüdiger, Thomas; Rudolph, Anja; Ruebner, Matthias; Rutgers, Emiel J. T.; Saloustros, Emmanouil; Sandler, Dale P.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schumacher, Fredrick; Schürmann, Peter; Scott, Rodney J.; Scott, Christopher; Seal, Sheila; Seynaeve, Caroline; Shah, Mitul; Sharma, Priyanka; Shen, Chen-Yang; Sheng, Grace; Sherman, Mark E.; Shrubsole, Martha J.; Shu, Xiao-Ou; Smeets, Ann; Sohn, Christof; Southey, Melissa C.; Spinelli, John J.; Stegmaier, Christa; Stewart-Brown, Sarah; Stone, Jennifer; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Tamimi, Rulla; Taylor, Jack A.; Tengström, Maria; teo, Soo H.; Beth Terry, Mary; Tessier, Daniel C.; Thanasitthichai, Somchai; Thöne, Kathrin; Tollenaar, Rob A. E. M.; Tomlinson, Ian; Tong, Ling; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Tsugane, Shoichiro; Ulmer, Hans-Ulrich; Ursin, Giske; Untch, Michael; Vachon, Celine; van Asperen, Christi J.; van den Berg, David; van den Ouweland, Ans M. W.; van der Kolk, Lizet; van der Luijt, Rob B.; Vincent, Daniel; Vollenweider, Jason; Waisfisz, Quinten; Wang-Gohrke, Shan; Weinberg, Clarice R.; Wendt, Camilla; Whittemore, Alice S.; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Wolk, Alicja; Wu, Anna H.; Xia, Lucy; Yamaji, Taiki; Yang, Xiaohong R.; Har Yip, Cheng; Yoo, Keun-Young; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Zhu, Bin; Ziogas, Argyrios; Ziv, Elad; Lakhani, Sunil R.; Antoniou, Antonis C.; Droit, Arnaud; Andrulis, Irene L.; Amos, Christopher I.; Couch, Fergus J.; Pharoah, Paul D. P.; Chang-Claude, Jenny; Hall, Per; Hunter, David J.; Milne, Roger L.; García-Closas, Montserrat; Schmidt, Marjanka K.; Chanock, Stephen J.; Dunning, Alison M.; Edwards, Stacey L.; Bader, Gary D.; Chenevix-Trench, Georgia; Simard, Jacques; Kraft, Peter; Easton, Douglas F.

    2017-01-01

    Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast

  4. A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability.

    Science.gov (United States)

    Chen, Huan; Gu, Xiao-Hong; Zhou, Yuxi; Ge, Zeng; Wang, Bin; Siok, Wai Ting; Wang, Guoqing; Huen, Michael; Jiang, Yuyang; Tan, Li-Hai; Sun, Yimin

    2017-02-03

    Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) of SPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10 -10 , maximum β -2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level.

  5. Genome-wide association study identifies 74 loci associated with educational attainment

    DEFF Research Database (Denmark)

    Okbay, Aysu; P. Beauchamp, Jonathan; Alan Fontana, Mark

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends...... development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals...

  6. Identifying species conservation strategies to reduce disease-associated declines

    Science.gov (United States)

    Gerber, Brian D.; Converse, Sarah J.; Muths, Erin L.; Crockett, Harry J.; Mosher, Brittany A.; Bailey, Larissa L.

    2018-01-01

    Emerging infectious diseases (EIDs) are a salient threat to many animal taxa, causing local and global extinctions, altering communities and ecosystem function. The EID chytridiomycosis is a prominent driver of amphibian declines, which is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). To guide conservation policy, we developed a predictive decision-analytic model that combines empirical knowledge of host-pathogen metapopulation dynamics with expert judgment regarding effects of management actions, to select from potential conservation strategies. We apply our approach to a boreal toad (Anaxyrus boreas boreas) and Bd system, identifying optimal strategies that balance tradeoffs in maximizing toad population persistence and landscape-level distribution, while considering costs. The most robust strategy is expected to reduce the decline of toad breeding sites from 53% to 21% over 50 years. Our findings are incorporated into management policy to guide conservation planning. Our online modeling application provides a template for managers of other systems challenged by EIDs.

  7. Identifying species conservation strategies to reduce disease-associated declines

    Science.gov (United States)

    Gerber, Brian D.; Converse, Sarah J.; Muths, Erin L.; Crockett, Harry J.; Mosher, Brittany A.; Bailey, Larissa L.

    2017-01-01

    Emerging infectious diseases (EIDs) are a salient threat to many animal taxa, causing local and global extinctions, altering communities and ecosystem function. The EID chytridiomycosis is a prominent driver of amphibian declines, which is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). To guide conservation policy, we developed a predictive decision-analytic model that combines empirical knowledge of host-pathogen metapopulation dynamics with expert judgment regarding effects of management actions, to select from potential conservation strategies. We apply our approach to a boreal toad (Anaxyrus boreas boreas) and Bd system, identifying optimal strategies that balance tradeoffs in maximizing toad population persistence and landscape-level distribution, while considering costs. The most robust strategy is expected to reduce the decline of toad breeding sites from 53% to 21% over 50 years. Our findings are incorporated into management policy to guide conservation planning. Our online modeling application provides a template for managers of other systems challenged by EIDs.

  8. Genome-wide association study identifies 74 loci associated with educational attainment

    OpenAIRE

    Okbay, Aysu; Beauchamp, Jonathan; Fontana, M.A. (Mark Alan); Lee, James J.; Pers, Tune; Rietveld, C.A. (Cornelius A.); Turley, Patrick; Chen, G.-B. (Guo-Bo); Emilsson, Valur; Meddens, S.F.W. (S. Fleur W.); Oskarsson, S. (Sven); Pickrell, J.K. (Joseph K.); Thom, K. (Kevin); Timshel, P. (Pascal); Vlaming, Ronald

    2016-01-01

    textabstractEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 geno...

  9. Identifying associations between sport sponsorship decision-making variables

    Directory of Open Access Journals (Sweden)

    CH Van Heerden

    2004-04-01

    Full Text Available Sport sponsorship spending in South Africa has increased steadily. This paper discusses the findings of an exploratory study into key sponsorship decision-areas, namely the setting of sponsorship objectives, the integration of marketing communication variables into sponsorship to create a leverage effect, and the measurement of sponsorship success. It is argued that for a sponsorship to be successful certain associations should exist between these key decision-making areas and also among elements internal to each of these areas. The main findings are that the respondents indicated a bias towards setting media related objectives that will subsequently enable the sponsors to use media-related measurement tools. It is recommended that sponsors should develop alternative methods to measure the effectiveness of their sponsorships.

  10. Genome-wide association study identifies 74 loci associated with educational attainment.

    Science.gov (United States)

    Okbay, Aysu; Beauchamp, Jonathan P; Fontana, Mark Alan; Lee, James J; Pers, Tune H; Rietveld, Cornelius A; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S Fleur W; Oskarsson, Sven; Pickrell, Joseph K; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H; Pina Concas, Maria; Derringer, Jaime; Furlotte, Nicholas A; Galesloot, Tessel E; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M; Harris, Sarah E; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E; Kaasik, Kadri; Kalafati, Ioanna P; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J; deLeeuw, Christiaan; Lind, Penelope A; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B; van der Most, Peter J; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Börge; Schraut, Katharina E; Shi, Jianxin; Smith, Albert V; Poot, Raymond A; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E; Biino, Ginevra; Bønnelykke, Klaus; Boyle, Patricia A; Campbell, Harry; Cappuccio, Francesco P; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M; Faul, Jessica D; Feitosa, Mary F; Forstner, Andreas J; Gandin, Ilaria; Gunnarsson, Bjarni; Halldórsson, Bjarni V; Harris, Tamara B; Heath, Andrew C; Hocking, Lynne J; Holliday, Elizabeth G; Homuth, Georg; Horan, Michael A; Hottenga, Jouke-Jan; de Jager, Philip L; Joshi, Peter K; Jugessur, Astanand; Kaakinen, Marika A; Kähönen, Mika; Kanoni, Stavroula; Keltigangas-Järvinen, Liisa; Kiemeney, Lambertus A L M; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J; Lebreton, Maël P; Levinson, Douglas F; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C M; Loukola, Anu; Madden, Pamela A; Mägi, Reedik; Mäki-Opas, Tomi; Marioni, Riccardo E; Marques-Vidal, Pedro; Meddens, Gerardus A; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W; Myhre, Ronny; Nelson, Christopher P; Nyholt, Dale R; Ollier, William E R; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L; Petrovic, Katja E; Porteous, David J; Räikkönen, Katri; Ring, Susan M; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J; Smith, Blair H; Smith, Jennifer A; Staessen, Jan A; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J A; Venturini, Cristina; Vinkhuyzen, Anna A E; Völker, Uwe; Völzke, Henry; Vonk, Judith M; Vozzi, Diego; Waage, Johannes; Ware, Erin B; Willemsen, Gonneke; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I; Borecki, Ingrid B; Bültmann, Ute; Chabris, Christopher F; Cucca, Francesco; Cusi, Daniele; Deary, Ian J; Dedoussis, George V; van Duijn, Cornelia M; Eriksson, Johan G; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V; Gieger, Christian; Grabe, Hans-Jörgen; Gratten, Jacob; Groenen, Patrick J F; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A; Hoffmann, Wolfgang; Hyppönen, Elina; Iacono, William G; Jacobsson, Bo; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Lehtimäki, Terho; Lehrer, Steven F; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W J H; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A; Samani, Nilesh J; Schlessinger, David; Schmidt, Reinhold; Sørensen, Thorkild I A; Spector, Tim D; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Tung, Joyce Y; Uitterlinden, André G; Vitart, Veronique; Vollenweider, Peter; Weir, David R; Wilson, James F; Wright, Alan F; Conley, Dalton C; Krueger, Robert F; Davey Smith, George; Hofman, Albert; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Yang, Jian; Johannesson, Magnus; Visscher, Peter M; Esko, Tõnu; Koellinger, Philipp D; Cesarini, David; Benjamin, Daniel J

    2016-05-26

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

  11. Genome-wide association study identifies 74 loci associated with educational attainment

    Science.gov (United States)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark A.; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Börge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bønnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans68, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldórsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kähönen, Mika; Kanoni, Stavroula; Keltigangas-Järvinen, Liisa; Kiemeney, Lambertus A.L.M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Maël P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C.M.; Loukola, Anu; Madden, Pamela A.; Mägi, Reedik; Mäki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E.R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Räikkönen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J.A.; Venturini, Cristina; Vinkhuyzen, Anna A.E.; Völker, Uwe; Völzke, Henry; Vonk, Judith M.; Vozzi, Diego; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jörgen; Gratten, Jacob; Groenen, Patrick J.F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppönen, Elina; Iacono, William G.; Jacobsson, Bo; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L.R.; Lehtimäki, Terho; Lehrer, Steven F.; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W.J.H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sørensen, Thorkild I.A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, André G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tõnu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Summary Educational attainment (EA) is strongly influenced by social and other environmental factors, but genetic factors are also estimated to account for at least 20% of the variation across individuals1. We report the results of a genome-wide association study (GWAS) for EA that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication in an independent sample of 111,349 individuals from the UK Biobank. We now identify 74 genome-wide significant loci associated with number of years of schooling completed. Single-nucleotide polymorphisms (SNPs) associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioral phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because EA is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric disease. PMID:27225129

  12. Genome-wide association study identifies five new schizophrenia loci

    DEFF Research Database (Denmark)

    Ripke, Stephan; Sanders, Alan R; Kendler, Kenneth S

    2011-01-01

    in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).......We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis...... an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism...

  13. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

    DEFF Research Database (Denmark)

    Ahmetov, Ii; Kulemin, Na; Popov, Dv

    2015-01-01

    To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate ([Formula: see text]O2......max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P endurance athletes and opposite cohorts (192...... Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six 'endurance alleles' were identified showing discrete associations with [Formula: see text]O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs...

  14. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.

    Science.gov (United States)

    Lu, Yi; Vitart, Veronique; Burdon, Kathryn P; Khor, Chiea Chuen; Bykhovskaya, Yelena; Mirshahi, Alireza; Hewitt, Alex W; Koehn, Demelza; Hysi, Pirro G; Ramdas, Wishal D; Zeller, Tanja; Vithana, Eranga N; Cornes, Belinda K; Tay, Wan-Ting; Tai, E Shyong; Cheng, Ching-Yu; Liu, Jianjun; Foo, Jia-Nee; Saw, Seang Mei; Thorleifsson, Gudmar; Stefansson, Kari; Dimasi, David P; Mills, Richard A; Mountain, Jenny; Ang, Wei; Hoehn, René; Verhoeven, Virginie J M; Grus, Franz; Wolfs, Roger; Castagne, Raphaële; Lackner, Karl J; Springelkamp, Henriët; Yang, Jian; Jonasson, Fridbert; Leung, Dexter Y L; Chen, Li J; Tham, Clement C Y; Rudan, Igor; Vatavuk, Zoran; Hayward, Caroline; Gibson, Jane; Cree, Angela J; MacLeod, Alex; Ennis, Sarah; Polasek, Ozren; Campbell, Harry; Wilson, James F; Viswanathan, Ananth C; Fleck, Brian; Li, Xiaohui; Siscovick, David; Taylor, Kent D; Rotter, Jerome I; Yazar, Seyhan; Ulmer, Megan; Li, Jun; Yaspan, Brian L; Ozel, Ayse B; Richards, Julia E; Moroi, Sayoko E; Haines, Jonathan L; Kang, Jae H; Pasquale, Louis R; Allingham, R Rand; Ashley-Koch, Allison; Mitchell, Paul; Wang, Jie Jin; Wright, Alan F; Pennell, Craig; Spector, Timothy D; Young, Terri L; Klaver, Caroline C W; Martin, Nicholas G; Montgomery, Grant W; Anderson, Michael G; Aung, Tin; Willoughby, Colin E; Wiggs, Janey L; Pang, Chi P; Thorsteinsdottir, Unnur; Lotery, Andrew J; Hammond, Christopher J; van Duijn, Cornelia M; Hauser, Michael A; Rabinowitz, Yaron S; Pfeiffer, Norbert; Mackey, David A; Craig, Jamie E; Macgregor, Stuart; Wong, Tien Y

    2013-02-01

    Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

  15. Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies.

    Directory of Open Access Journals (Sweden)

    Longjuan Qin

    Full Text Available Genome-wide association studies (GWASs have revealed many SNPs and genes associated with osteoporosis. However, influence of these SNPs and genes on the predisposition to osteoporosis is not fully understood. We aimed to identify osteoporosis GWASs-associated SNPs potentially influencing the binding affinity of transcription factors and miRNAs, and reveal enrichment signaling pathway and "hub" genes of osteoporosis GWAS-associated genes.We conducted multiple computational analyses to explore function and mechanisms of osteoporosis GWAS-associated SNPs and genes, including SNP conservation analysis and functional annotation (influence of SNPs on transcription factors and miRNA binding, gene ontology analysis, pathway analysis and protein-protein interaction analysis.Our results suggested that a number of SNPs potentially influence the binding affinity of transcription factors (NFATC2, MEF2C, SOX9, RUNX2, ESR2, FOXA1 and STAT3 and miRNAs. Osteoporosis GWASs-associated genes showed enrichment of Wnt signaling pathway, basal cell carcinoma and Hedgehog signaling pathway. Highly interconnected "hub" genes revealed by interaction network analysis are RUNX2, SP7, TNFRSF11B, LRP5, DKK1, ESR1 and SOST.Our results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology.

  16. Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies.

    Science.gov (United States)

    Qin, Longjuan; Liu, Yuyong; Wang, Ya; Wu, Guiju; Chen, Jie; Ye, Weiyuan; Yang, Jiancai; Huang, Qingyang

    2016-01-01

    Genome-wide association studies (GWASs) have revealed many SNPs and genes associated with osteoporosis. However, influence of these SNPs and genes on the predisposition to osteoporosis is not fully understood. We aimed to identify osteoporosis GWASs-associated SNPs potentially influencing the binding affinity of transcription factors and miRNAs, and reveal enrichment signaling pathway and "hub" genes of osteoporosis GWAS-associated genes. We conducted multiple computational analyses to explore function and mechanisms of osteoporosis GWAS-associated SNPs and genes, including SNP conservation analysis and functional annotation (influence of SNPs on transcription factors and miRNA binding), gene ontology analysis, pathway analysis and protein-protein interaction analysis. Our results suggested that a number of SNPs potentially influence the binding affinity of transcription factors (NFATC2, MEF2C, SOX9, RUNX2, ESR2, FOXA1 and STAT3) and miRNAs. Osteoporosis GWASs-associated genes showed enrichment of Wnt signaling pathway, basal cell carcinoma and Hedgehog signaling pathway. Highly interconnected "hub" genes revealed by interaction network analysis are RUNX2, SP7, TNFRSF11B, LRP5, DKK1, ESR1 and SOST. Our results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology.

  17. A genome-wide association scan in pig identifies novel regions associated with feed efficiency trait

    DEFF Research Database (Denmark)

    Sahana, Goutam; Kadlecová, Veronika; Hornshøj, Henrik

    2013-01-01

    and to study the genetic architecture of the trait. After quality control, a total of 30,847 SNPs that could be mapped to the 18 porcine autosomes (SSC) following the pig genome assembly 10.2, were used in the analyses. Deregressed estimated breeding value was used as the response variable. A total of 3......Feed conversion ratio (FCR) is an economically important trait in pigs and feed accounts for a significant proportion of the costs involved in pig production. In this study we used a high density SNP chip panel, Porcine SNP60 BeadChip, to identify association between FCR and SNP markers...

  18. 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.

  19. Strongest Tropical cyclones: 1980-2009: A 30-year collage of Hurricane Satellite (HURSAT) data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Strongest Tropical Cyclones: 1980-2009 poster - a 30-year collage of Hurricane Satellite (HURSAT) data. This poster depicts a series of 5 degree grids where within...

  20. 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.

  1. A genome-wide association study identifies multiple loci associated with mathematics ability and disability.

    Science.gov (United States)

    Docherty, S J; Davis, O S P; Kovas, Y; Meaburn, E L; Dale, P S; Petrill, S A; Schalkwyk, L C; Plomin, R

    2010-03-01

    Numeracy is as important as literacy and exhibits a similar frequency of disability. Although its etiology is relatively poorly understood, quantitative genetic research has demonstrated mathematical ability to be moderately heritable. In this first genome-wide association study (GWAS) of mathematical ability and disability, 10 out of 43 single nucleotide polymorphism (SNP) associations nominated from two high- vs. low-ability (n = 600 10-year-olds each) scans of pooled DNA were validated (P mathematical ability, as assessed by teacher reports and online tests. Although the effects are of the modest sizes now expected for complex traits and require further replication, interesting candidate genes are implicated such as NRCAM which encodes a neuronal cell adhesion molecule. When combined into a set, the 10 SNPs account for 2.9% (F = 56.85; df = 1 and 1881; P = 7.277e-14) of the phenotypic variance. The association is linear across the distribution consistent with a quantitative trait locus (QTL) hypothesis; the third of children in our sample who harbour 10 or more of the 20 risk alleles identified are nearly twice as likely (OR = 1.96; df = 1; P = 3.696e-07) to be in the lowest performing 15% of the distribution. Our results correspond with those of quantitative genetic research in indicating that mathematical ability and disability are influenced by many genes generating small effects across the entire spectrum of ability, implying that more highly powered studies will be needed to detect and replicate these QTL associations.

  2. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

    Science.gov (United States)

    Lu, Yi; Vitart, Veronique; Burdon, Kathryn P; Khor, Chiea Chuen; Bykhovskaya, Yelena; Mirshahi, Alireza; Hewitt, Alex W; Koehn, Demelza; Hysi, Pirro G; Ramdas, Wishal D; Zeller, Tanja; Vithana, Eranga N; Cornes, Belinda K; Tay, Wan-Ting; Tai, E Shyong; Cheng, Ching-Yu; Liu, Jianjun; Foo, Jia-Nee; Saw, Seang Mei; Thorleifsson, Gudmar; Stefansson, Kari; Dimasi, David P; Mills, Richard A; Mountain, Jenny; Ang, Wei; Hoehn, René; Verhoeven, Virginie J M; Grus, Franz; Wolfs, Roger; Castagne, Raphaële; Lackner, Karl J; Springelkamp, Henriët; Yang, Jian; Jonasson, Fridbert; Leung, Dexter Y L; Chen, Li J; Tham, Clement C Y; Rudan, Igor; Vatavuk, Zoran; Hayward, Caroline; Gibson, Jane; Cree, Angela J; MacLeod, Alex; Ennis, Sarah; Polasek, Ozren; Campbell, Harry; Wilson, James F; Viswanathan, Ananth C; Fleck, Brian; Li, Xiaohui; Siscovick, David; Taylor, Kent D; Rotter, Jerome I; Yazar, Seyhan; Ulmer, Megan; Li, Jun; Yaspan, Brian L; Ozel, Ayse B; Richards, Julia E; Moroi, Sayoko E; Haines, Jonathan L; Kang, Jae H; Pasquale, Louis R; Allingham, R Rand; Ashley-Koch, Allison; Mitchell, Paul; Wang, Jie Jin; Wright, Alan F; Pennell, Craig; Spector, Timothy D; Young, Terri L; Klaver, Caroline C W; Martin, Nicholas G; Montgomery, Grant W; Anderson, Michael G; Aung, Tin; Willoughby, Colin E; Wiggs, Janey L; Pang, Chi P; Thorsteinsdottir, Unnur; Lotery, Andrew J; Hammond, Christopher J; van Duijn, Cornelia M; Hauser, Michael A; Rabinowitz, Yaron S; Pfeiffer, Norbert; Mackey, David A; Craig, Jamie E; Macgregor, Stuart; Wong, Tien Y

    2013-01-01

    Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4–1.88, P = 2.7 × 10−10, and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29–1.68, P = 4.9 × 10−9). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10−4; tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT. PMID:23291589

  3. Diffusive versus Displacive Contact Plasticity of Nanoscale Asperities: Temperature- and Velocity-Dependent Strongest Size.

    Science.gov (United States)

    Guo, Wei; Wang, Zhao; Li, Ju

    2015-10-14

    We predict a strongest size for the contact strength when asperity radii of curvature decrease below 10 nm. The reason for such strongest size is found to be correlated with the competition between the dislocation plasticity and surface diffusional plasticity. The essential role of temperature is calculated and illustrated in a comprehensive asperity size-strength-temperature map taking into account the effect of contact velocity. Such a map should be essential for various phenomena related to nanoscale contacts such as nanowire cold welding, self-assembly of nanoparticles and adhesive nanopillar arrays, as well as the electrical, thermal, and mechanical properties of macroscopic interfaces.

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

    NARCIS (Netherlands)

    Kraja, Aldi T; Cook, James P; Warren, Helen R; Surendran, Praveen; Liu, Chunyu; Evangelou, Evangelos; Manning, Alisa K; Grarup, Niels; Drenos, Fotios; Sim, Xueling; Smith, Albert Vernon; Amin, Najaf; Blakemore, Alexandra I F; Bork-Jensen, Jette; Brandslund, Ivan; Farmaki, Aliki-Eleni; Fava, Cristiano; Ferreira, Teresa; Herzig, Karl-Heinz; Giri, Ayush; Giulianini, Franco; Grove, Megan L; Guo, Xiuqing; Harris, Sarah E; Have, Christian T; Havulinna, Aki S; Zhang, He; Jørgensen, Marit E; Käräjämäki, AnneMari; Kooperberg, Charles; Linneberg, Allan; Little, Louis; Liu, Yongmei; Bonnycastle, Lori L; Lu, Yingchang; Mägi, Reedik; Mahajan, Anubha; Malerba, Giovanni; Marioni, Riccardo E; Mei, Hao; Menni, Cristina; Morrison, Alanna C; Padmanabhan, Sandosh; Palmas, Walter; Poveda, Alaitz; Rauramaa, Rainer; Rayner, Nigel William; Riaz, Muhammad; Rice, Ken; Richard, Melissa A; Smith, Jennifer A; Southam, Lorraine; Stančáková, Alena; Stirrups, Kathleen E; Tragante, Vinicius; Tuomi, Tiinamaija; Tzoulaki, Ioanna; Varga, Tibor V; Weiss, Stefan; Yiorkas, Andrianos M; Young, Robin; Zhang, Weihua; Barnes, Michael R; Cabrera, Claudia P; Gao, He; Boehnke, Michael; Boerwinkle, Eric; Chambers, John C; Connell, John M; Christensen, Cramer K; de Boer, Rudolf A; Deary, Ian J; Dedoussis, George; Deloukas, Panos; Dominiczak, Anna F; Dörr, Marcus; Joehanes, Roby; Edwards, Todd L; Esko, Tõnu; Fornage, Myriam; Franceschini, Nora; Franks, Paul W; Gambaro, Giovanni; Groop, Leif; Hallmans, Göran; Hansen, Torben; Hayward, Caroline; Heikki, Oksa; Ingelsson, Erik; Tuomilehto, Jaakko; Jarvelin, Marjo-Riitta; Kardia, Sharon L R; Karpe, Fredrik; Kooner, Jaspal S; Lakka, Timo A; Langenberg, Claudia; Lind, Lars; Loos, Ruth J F; Laakso, Markku; McCarthy, Mark I; Melander, Olle; Mohlke, Karen L; Morris, Andrew P; Palmer, Colin N A; Pedersen, Oluf; Polasek, Ozren; Poulter, Neil R; Province, Michael A; Psaty, Bruce M; Ridker, Paul M; Rotter, Jerome I; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Sever, Peter J; Skaaby, Tea; Stafford, Jeanette M; Starr, John M; van der Harst, Pim; van der Meer, Peter; van Duijn, Cornelia M; Vergnaud, Anne-Claire; Gudnason, Vilmundur; Wareham, Nicholas J; Wilson, James G; Willer, Cristen J; Witte, Daniel R; Zeggini, Eleftheria; Saleheen, Danish; Butterworth, Adam S; Danesh, John; Asselbergs, Folkert W; Wain, Louise V; Ehret, Georg B; Chasman, Daniel I; Caulfield, Mark J; Elliott, Paul; Lindgren, Cecilia M; Levy, Daniel; Newton-Cheh, Christopher; Munroe, Patricia B; Howson, Joanna M M

    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. An

  5. Genome-wide association identifies a deletion in the 3' untranslated region of striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy.

    Science.gov (United States)

    Meurs, Kathryn M; Mauceli, Evan; Lahmers, Sunshine; Acland, Gregory M; White, Stephen N; Lindblad-Toh, Kerstin

    2010-09-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease characterized by ventricular arrhythmias and sudden cardiac death. It is most frequently inherited as an autosomal dominant trait with incomplete and age-related penetrance and variable clinical expression. The human disease is most commonly associated with a causative mutation in one of several genes encoding desmosomal proteins. We have previously described a spontaneous canine model of ARVC in the boxer dog. We phenotyped adult boxer dogs for ARVC by performing physical examination, echocardiogram and ambulatory electrocardiogram. Genome-wide association using the canine 50k SNP array identified several regions of association, of which the strongest resided on chromosome 17. Fine mapping and direct DNA sequencing identified an 8-bp deletion in the 3' untranslated region (UTR) of the Striatin gene on chromosome 17 in association with ARVC in the boxer dog. Evaluation of the secondary structure of the 3' UTR demonstrated that the deletion affects a stem loop structure of the mRNA and expression analysis identified a reduction in Striatin mRNA. Dogs that were homozygous for the deletion had a more severe form of disease based on a significantly higher number of ventricular premature complexes. Immunofluorescence studies localized Striatin to the intercalated disc region of the cardiac myocyte and co-localized it to three desmosomal proteins, Plakophilin-2, Plakoglobin and Desmoplakin, all involved in the pathogenesis of ARVC in human beings. We suggest that Striatin may serve as a novel candidate gene for human ARVC.

  6. Complete re-sequencing of a 2Mb topological domain encompassing the FTO/IRXB genes identifies a novel obesity-associated region upstream of IRX5

    DEFF Research Database (Denmark)

    Hunt, Lilian E; Noyvert, Boris; Bhaw-Rosun, Leena

    2015-01-01

    implicated in the aetiology of obesity. METHODS: Here, we sequence a 2 Mb region encompassing the FTO, RPGRIP1L and IRXB cluster genes in 284 individuals from a well-characterised study group of Danish men containing extremely overweight young adults and controls. We further replicate our findings both......BACKGROUND: Association studies have identified a number of loci that contribute to an increased body mass index (BMI), the strongest of which is in the first intron of the FTO gene on human chromosome 16q12.2. However, this region is both non-coding and under strong linkage disequilibrium, making...... in an expanded male cohort and an independent female study group. Finally, we compare our variant data with a previous study describing IRX3 and FTO interactions in this region. RESULTS: We obtain deep coverage across the entire region, allowing accurate and unequivocal determination of almost every single...

  7. Establishment of Interdisciplinary Child Protection Teams in Turkey 2002-2006: Identifying the Strongest Link Can Make a Difference!

    Science.gov (United States)

    Agirtan, Canan A.; Akar, Taner; Akbas, Seher; Akdur, Recep; Aydin, Cahide; Aytar, Gulsen; Ayyildiz, Suat; Baskan, Sevgi; Belgemen, Tugba; Bezirci, Ozdecan; Beyazova, Ufuk; Beyaztas, Fatma Yucel; Buken, Bora; Buken, Erhan; Camurdan, Aysu D.; Can, Demet; Canbaz, Sevgi; Canturk, Gurol; Ceyhan, Meltem; Coskun, Abdulhakim; Celik, Ahmet; Cetin, Fusun C.; Coskun, Ayse Gul; Dagcinar, Adnan; Dallar, Yildiz; Demirel, Birol; Demirogullari, Billur; Derman, Orhan; Dilli, Dilek; Ersahin, Yusuf; Esiyok, Burcu; Evinc, Gulin; Gencer, Ozlem; Gokler, Bahar; Hanci, Hamit; Iseri, Elvan; Isir, Aysun Baransel; Isiten, Nukhet; Kale, Gulsev; Karadag, Ferda; Kanbur, Nuray; Kilic, Birim; Kultur, Ebru; Kurtay, Derya; Kuruoglu, Asli; Miral, Suha; Odabasi, Aysun B.; Oral, Resmiye; Orhon, Filiz Simsek; Ozbesler, Cengiz; Ozdemir, Dilsad Foto; Ozkok, M. Selim; Ozmert, Elif; Oztop, Didem B.; Ozyurek, Hamit; Pasli, Figen; Peksen, Yildiz; Polat, Onur; Sahin, Figen; Sahin, Ahmet Rifat; Salacin, Serpil; Suskan, Emine; Tander, Burak; Tekin, Deniz; Teksam, Ozlem; Tiras, Ulku; Tomak, Yilmaz; Tumer, Ali Riza; Turla, Ahmet; Ulukol, Betul; Uslu, Runa; Tas, Fatma V.; Vatandas, Nilgun; Velipasaoglu, Sevtap; Yagmur, Fatih; Yagmurlu, Aydin; Yalcin, Songul; Yavuz, Sukruye; Yurdakok, Kadriye

    2009-01-01

    Objectives: The University of Iowa Child Protection Program collaborated with Turkish professionals to develop a training program on child abuse and neglect during 2002-2006 with the goals of increasing professional awareness and number of multidisciplinary teams (MDT), regional collaborations, and assessed cases. This paper summarizes the 5-year…

  8. Education is the strongest socio-economic predictor of smoking in pregnancy.

    Science.gov (United States)

    Härkönen, Juho; Lindberg, Matti; Karlsson, Linnea; Karlsson, Hasse; Scheinin, Noora M

    2018-01-14

    To investigate socio-economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions. Cross-sectional analysis with linked survey and register data. South-western Finland. A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study. The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire-based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio-economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated. Mother's education was the strongest socio-economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2-3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1-9.0; P education, 2.9 (95% CI = 1.4-6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0-18.2; P education and 14.4 (95% CI = 6.3-33.0; P education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1-3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4-2.8; P pregnancy are attributable primarily to differences in the mother's educational level (low versus high) and orientation (vocational versus general). © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study

  9. Genome-wide association analysis identifies six new loci associated with forced vital capacity

    NARCIS (Netherlands)

    D.W. Loth (Daan); M.S. Artigas; S.A. Gharib (Sina); L.V. Wain (Louise); N. Franceschini (Nora); B. Koch (Beate); T.D. Pottinger (Tess); G.D. Smith; Q. Duan (Qing); C. Oldmeadow (Christopher); M.K. Lee (Mi Kyeong); D.P. Strachan (David); A.L. James (Alan); J.E. Huffman (Jennifer); V. Vitart (Veronique); A. Ramasamy (Adaikalavan); N.J. Wareham (Nick); J. Kaprio (Jaakko); X.-Q. Wang (Xin-Qun); H. Trochet (Holly); M. Kähönen (Mika); C. Flexeder (Claudia); E. Albrecht (Eva); L.M. Lopez (Lorna); B. Thyagarajan (Bharat); A.C. Alves (Alexessander Couto); S. Enroth (Stefan); E. Omenaas (Ernst); P.K. Joshi (Peter); M. Fall (Magnus); A. Viñuela (Ana); L.J. Launer (Lenore); L.R. Loehr (Laura); M. Fornage (Myriam); G. Li (Guo); J.B. Wilk (Jemma); W. Tang (Wenbo); A. Manichaikul (Ani); L. Lahousse (Lies); T.B. Harris (Tamara); K.E. North (Kari); A.R. Rudnicka (Alicja); J. Hui (Jennie); X. Gu (Xiangjun); T. Lumley (Thomas); A.F. Wright (Alan); N. Hastie (Nick); S. Campbell (Susan); R. Kumar (Rajesh); I. Pin (Isabelle); R.A. Scott (Robert); K.H. Pietilainen (Kirsi Hannele); I. Surakka (Ida); Y. Liu (YongMei); E.G. Holliday (Elizabeth); H. Schulz (Holger); J. Heinrich (Joachim); G. Davies (Gail); J.M. Vonk (Judith); M.K. Wojczynski (Mary ); A. Pouta (Anneli); A. Johansson (Åsa); S.H. Wild (Sarah); E. Ingelsson (Erik); F. Rivadeneira Ramirez (Fernando); H. Völzke (Henry); P.G. Hysi (Pirro); G. Eiriksdottir (Gudny); A.C. Morrison (Alanna); J.I. Rotter (Jerome); W. Gao (Wei); D.S. Postma (Dirkje); W.B. White (Wendy); S.S. Rich (Stephen); A. Hofman (Albert); T. Aspelund (Thor); D. Couper (David); L.J. Smith (Lewis); B.M. Psaty (Bruce); K. Lohman (Kurt); E.G. Burchard (Esteban); A.G. Uitterlinden (André); M. Garcia (Melissa); B.R. Joubert (Bonnie); W.L. McArdle (Wendy); A.W. Musk (Arthur); C.R.W. Hansel (Christian); S.R. Heckbert (Susan); L. Zgaga (Lina); J.B.J. van Meurs (Joyce); P. Navarro (Pau); I. Rudan (Igor); Y.-M. Oh (Yeon-Mok); S. Redline (Susan); D.L. Jarvis (Deborah); J.H. Zhao (Jing Hua); T. Rantanen (Taina); G.T. O'Connor (George); S. Ripatti (Samuli); R.J. Scott (Rodney); S. Karrasch (Stefan); H. Grallert (Harald); N.C. Gaddis (Nathan); J.M. Starr (John); C. Wijmenga (Cisca); R.L. Minster (Ryan); C.W. Lederer (Carsten); J. Pekkanen (Juha); U. Gyllensten (Ulf); H. Campbell (Harry); A.P. Morris (Andrew); S. Gläser (Sven); C.J. Hammond (Christopher); K.M. Burkart (Kristin); J.P. Beilby (John); S.B. Kritchevsky (Stephen); V. Gudnason (Vilmundur); D.B. Hancock (Dana); O.D. Williams (Dale); O. Polasek (Ozren); T. Zemunik (Tatijana); I. Kolcic (Ivana); M.F. Petrini (Marcy); K.T. de Jong (Kim); M. Wjst (Matthias); W.H. Kim (Woo); D.J. Porteous (David J.); G. Scotland (Generation); B.H. Smith (Blair); A. Viljanen (Anne); M. Heliovaara (Markku); J. Attia (John); I. Sayers (Ian); R. Hampel (Regina); C. Gieger (Christian); I.J. Deary (Ian); H.M. Boezen (Marike); A.B. Newman (Anne); M.-R. Jarvelin (Marjo-Riitta); J.F. Wilson (James); L. Lind (Lars); B.H.Ch. Stricker (Bruno); A. Teumer (Alexander); T.D. Spector (Timothy); E. Melén (Erik); M.J. Peters (Marjolein); L.A. Lange (Leslie); R.G. Barr (Graham); K.R. Bracke (Ken); F.M. Verhamme (Fien); J. Sung (Joohon); P.S. Hiemstra (Pieter); P.A. Cassano (Patricia); A. Sood (Akshay); C. Hayward (Caroline); J. Dupuis (Josée); I.P. Hall (Ian); G.G. Brusselle (Guy); M.D. Tobin (Martin); S.J. London (Stephanie)

    2014-01-01

    textabstractForced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in

  10. Genome-wide association analysis identifies six new loci associated with forced vital capacity

    NARCIS (Netherlands)

    Loth, Daan W.; Artigas, Maria Soler; Gharib, Sina A.; Wain, Louise V.; Franceschini, Nora; Koch, Beate; Pottinger, Tess D.; Smith, Albert Vernon; Duan, Qing; Oldmeadow, Chris; Lee, Mi Kyeong; Strachan, David P.; James, Alan L.; Huffman, Jennifer E.; Vitart, Veronique; Ramasamy, Adaikalavan; Wareham, Nicholas J.; Kaprio, Jaakko; Wang, Xin-Qun; Trochet, Holly; Kaonen, Mika; Flexeder, Claudia; Albrecht, Eva; Lopez, Lorna M.; de Jong, Kim; Thyagarajan, Bharat; Alves, Alexessander Couto; Enroth, Stefan; Omenaas, Ernst; Joshi, Peter K.; Fall, Tove; Vinuela, Ana; Launer, Lenore J.; Loehr, Laura R.; Fornage, Myriam; Li, Guo; Wik, Jemma B.; Tang, Wenbo; Manichaikul, Ani; Lahousse, Lies; Harris, Tamara B.; North, Kari E.; Rudnicka, Alicja R.; Hui, Jennie; Gu, Xiangjun; Lumley, Thomas; Wright, Alan F.; Hastie, Nicholas D.; Campbell, Susan; Kumar, Rajesh; Pin, Isabelle; Scott, Robert A.; Pietilainen, Kirsi H.; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G.; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M.; Wojczynski, Mary; Pouta, Anneli; Johansson, Asa; Wild, Sarah H.; Ingelsson, Erik; Rivadeneira, Fernando; Voezke, Henry; Hysi, Pirro G.; Eiriksdottir, Gudny; Morrison, Alanna C.; Rotter, Jerome I.; Gao, Wei; Postma, Dirkje S.; White, Wendy B.; Rich, Stephen S.; Hofman, Albert; Aspelund, Thor; Couper, David; Smith, Lewis J.; Psaty, Bruce M.; Lohman, Kurt; Burchard, Esteban G.; Uitterlinden, Andre G.; Garcia, Melissa; Joubert, Bonnie R.; McArdle, Wendy L.; Musk, A. Bill; Hansel, Nadia; Heckbert, Susan R.; Zgaga, Lina; van Meurs, Joyce B. J.; Navarro, Pau; Rudan, Igor; Oh, Yeon-Mok; Redline, Susan; Jarvis, Deborah L.; Rantanen, Taina; O'Connor, George T.; Ripatti, Samuli; Scott, Rodney J.; Karrasch, Stefan; Grallert, Harald; Gaddis, Nathan C.; Starr, John M.; Wijmenga, Cisca; Minster, Ryan L.; Lederer, David J.; Pekkanen, Juha; Gyllensten, Ulf; Campbe, Harry; Morris, Andrew P.; Glaeser, Sven; Hammond, Christopher J.; Burkart, Kristin M.; Beilby, John; Kritchevsky, Stephen B.; Gucinason, Vilrnundur; Hancock, Dana B.; Williams, Dale; Polasek, Ozren; Zemunik, Tatijana; Kolcic, Ivana; Petrini, Marcy F.; Wjst, Matthias; Kim, Woo Jin; Porteous, David J.; Scotland, Generation; Smith, Blair H.; Villanen, Anne; Heliovaara, Markku; Attia, John R.; Sayers, Ian; Hampel, Regina; Gieger, Christian; Deary, Ian J.; Boezen, Hendrika; Newman, Anne; Jarvelin, Marjo-Riitta; Wilson, James F.; Lind, Lars; Stricker, Bruno H.; Teumer, Alexander; Spector, Timothy D.; Melen, Erik; Peters, Marjolein J.; Lange, Leslie A.; Barr, R. Graham; Bracke, Ken R.; Verhamme, Fien M.; Sung, Joohon; Hiemstra, Pieter S.; Cassano, Patricia A.; Sood, Akshay; Hayward, Caroline; Dupuis, Josee; Hall, Ian P.; Brusselle, Guy G.; Tobin, Martin D.; London, Stephanie J.

    Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917

  11. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

    NARCIS (Netherlands)

    Chambers, John C.; Zhang, Weihua; Sehmi, Joban; Li, Xinzhong; Wass, Mark N.; van der Harst, Pim; Holm, Hilma; Sanna, Serena; Kavousi, Maryam; Baumeister, Sebastian E.; Coin, Lachlan J.; Deng, Guohong; Gieger, Christian; Heard-Costa, Nancy L.; Hottenga, Jouke-Jan; Kühnel, Brigitte; Kumar, Vinod; Lagou, Vasiliki; Liang, Liming; Luan, Jian'an; Vidal, Pedro Marques; Mateo Leach, Irene; O'Reilly, Paul F.; Peden, John F.; Rahmioglu, Nilufer; Soininen, Pasi; Speliotes, Elizabeth K.; Yuan, Xin; Thorleifsson, Gudmar; Alizadeh, Behrooz Z.; Atwood, Larry D.; Borecki, Ingrid B.; Brown, Morris J.; Charoen, Pimphen; Cucca, Francesco; Das, Debashish; de Geus, Eco J. C.; Dixon, Anna L.; Döring, Angela; Ehret, Georg; Eyjolfsson, Gudmundur I.; Farrall, Martin; Forouhi, Nita G.; Friedrich, Nele; Goessling, Wolfram; Gudbjartsson, Daniel F.; Harris, Tamara B.; Hartikainen, Anna-Liisa; Heath, Simon; Hirschfield, Gideon M.; Hofman, Albert; Homuth, Georg; Hyppönen, Elina; Janssen, Harry L. A.; Johnson, Toby; Kangas, Antti J.; Kema, Ido P.; Kühn, Jens P.; Lai, Sandra; Lathrop, Mark; Lerch, Markus M.; Li, Yun; Liang, T. Jake; Lin, Jing-Ping; Loos, Ruth J. F.; Martin, Nicholas G.; Moffatt, Miriam F.; Montgomery, Grant W.; Munroe, Patricia B.; Musunuru, Kiran; Nakamura, Yusuke; O'Donnell, Christopher J.; Olafsson, Isleifur; Penninx, Brenda W.; Pouta, Anneli; Prins, Bram P.; Prokopenko, Inga; Puls, Ralf; Ruokonen, Aimo; Savolainen, Markku J.; Schlessinger, David; Schouten, Jeoffrey N. L.; Seedorf, Udo; Sen-Chowdhry, Srijita; Siminovitch, Katherine A.; Smit, Johannes H.; Spector, Timothy D.; Tan, Wenting; Teslovich, Tanya M.; Tukiainen, Taru; Uitterlinden, Andre G.; van der Klauw, Melanie M.; Vasan, Ramachandran S.; Wallace, Chris; Wallaschofski, Henri; Wichmann, H.-Erich; Willemsen, Gonneke; Würtz, Peter; Xu, Chun; Yerges-Armstrong, Laura M.; Abecasis, Goncalo R.; Ahmadi, Kourosh R.; Boomsma, Dorret I.; Caulfield, Mark; Cookson, William O.; van Duijn, Cornelia M.; Froguel, Philippe; Matsuda, Koichi; McCarthy, Mark I.; Meisinger, Christa; Mooser, Vincent; Pietiläinen, Kirsi H.; Schumann, Gunter; Snieder, Harold; Sternberg, Michael J. E.; Stolk, Ronald P.; Thomas, Howard C.; Thorsteinsdottir, Unnur; Uda, Manuela; Waeber, Gérard; Wareham, Nicholas J.; Waterworth, Dawn M.; Watkins, Hugh; Whitfield, John B.; Witteman, Jacqueline C. M.; Wolffenbuttel, Bruce H. R.; Fox, Caroline S.; Ala-Korpela, Mika; Stefansson, Kari; Vollenweider, Peter; Völzke, Henry; Schadt, Eric E.; Scott, James; Järvelin, Marjo-Riitta; Elliott, Paul; Kooner, Jaspal S.; Voight, Benjamin F.; Scott, Laura J.; Steinthorsdottir, Valgerdur; Morris, Andrew P.; Dina, Christian; Welch, Ryan P.; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S.; Mcculloch, Laura J.; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J.; Raychaudhuri, Soumya; Mccarroll, Steve A.; Langenberg, Claudia; Hofmann, Oliver M.; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V.; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J.; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L.; Bengtsson Boström, Kristina; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P.; Charpentier, Guillaume; Chines, Peter S.; Cornelis, Marilyn; Couper, David J.; Crawford, Gabe; Doney, Alex S. F.; Elliott, Katherine S.; Elliott, Amanda L.; Erdos, Michael R.; Franklin, Christopher S.; Ganser, Martha; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J.; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U.; Johnson, Paul R. V.; Jørgensen, Torben; Kao, Wen H. L.; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M.; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A.; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R.; Payne, Felicity; Perry, John R. B.; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Rathmann, Wolfgang; William Rayner, N.; Robertson, Neil R.; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J.; Saxena, Richa; Shields, Beverley M.; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M.; Sun, Qi; Swift, Amy J.; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M.; van Haeften, Timon W.; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V.; Walters, G. Bragi; Weedon, Michael N.; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N.; Cauchi, Stephane; Collins, Francis S.; Gloyn, Anna L.; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A.; Hitman, Graham A.; Hunter, David J.; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L.; Morris, Andrew D.; Palmer, Colin N. A.; Pramstaller, Peter P.; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D.; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Watanabe, Richard M.; Boehm, Bernhard O.; Campbell, Harry; Daly, Mark J.; Hattersley, Andrew T.; Hu, Frank B.; Meigs, James B.; Pankow, James S.; Pedersen, Oluf; Barroso, Inês; Florez, Jose C.; Frayling, Timothy M.; Groop, Leif; Sladek, Rob; Wilson, James F.; Illig, Thomas; Altshuler, David; Boehnke, Michael; Lango Allen, H.; Estrada, K.; Lettre, G.; Berndt, S. I.; Weedon, M. N.; Rivadeneira, F.; Willer, C. J.; Jackson, A. U.; Vedantam, S.; Raychaudhuri, S.; Ferreira, T.; Wood, A. R.; Weyant, R. J.; Segrè, A. V.; Speliotes, E. K.; Wheeler, E.; Soranzo, N.; Park, J. H.; Yang, J.; Gudbjartsson, D.; Heard-Costa, N. L.; Randall, J. C.; Qi, L.; Smith, A. Vernon; Mägi, R.; Pastinen, T.; Liang, L.; Heid, I. M.; Luan, J.; Thorleifsson, G.; Winkler, T. W.; Goddard, M. E.; Sin Lo, K.; Palmer, C.; Workalemahu, T.; Aulchenko, Y. S.; Johansson, A.; Zillikens, M. C.; Feitosa, M. F.; Esko, T.; Johnson, T.; Ketkar, S.; Kraft, P.; Mangino, M.; Prokopenko, I.; Absher, D.; Albrecht, E.; Ernst, F.; Glazer, N. L.; Hayward, C.; Hottenga, J. J.; Jacobs, K. B.; Knowles, J. W.; Kutalik, Z.; Monda, K. L.; Polasek, O.; Preuss, M.; Rayner, N. W.; Robertson, N. R.; Steinthorsdottir, V.; Tyrer, J. P.; Voight, B. F.; Wiklund, F.; Xu, J.; Zhao, J. Hua; Nyholt, D. R.; Pellikka, N.; Perola, M.; Perry, J. R.; Surakka, I.; Tammesoo, M. L.; Altmaier, E. L.; Amin, N.; Aspelund, T.; Bhangale, T.; Boucher, G.; Chasman, D. I.; Chen, C.; Coin, L.; Cooper, M. N.; Dixon, A. L.; Gibson, Q.; Grundberg, E.; Hao, K.; Juhani Junttila, M.; Kaplan, L. M.; Kettunen, J.; König, I. R.; Kwan, T.; Lawrence, R. W.; Levinson, D. F.; Lorentzon, M.; McKnight, B.; Morris, A. P.; Müller, M.; Suh Ngwa, J.; Purcell, S.; Rafelt, S.; Salem, R. M.; Salvi, E.; Sanna, S.; Shi, J.; Sovio, U.; Thompson, J. R.; Turchin, M. C.; Vandenput, L.; Verlaan, D. J.; Vitart, V.; White, C. C.; Ziegler, A.; Almgren, P.; Balmforth, A. J.; Campbell, H.; Citterio, L.; de Grandi, A.; Dominiczak, A.; Duan, J.; Elliott, P.; Elosua, R.; Eriksson, J. G.; Freimer, N. B.; Geus, E. J.; Glorioso, N.; Haiqing, S.; Hartikainen, A. L.; Havulinna, A. S.; Hicks, A. A.; Hui, J.; Igl, W.; Illig, T.; Jula, A.; Kajantie, E.; Kilpeläinen, T. O.; Koiranen, M.; Kolcic, I.; Koskinen, S.; Kovacs, P.; Laitinen, J.; Liu, J.; Lokki, M. L.; Marusic, A.; Maschio, A.; Meitinger, T.; Mulas, A.; Paré, G.; Parker, A. N.; Peden, J. F.; Petersmann, A.; Pichler, I.; Pietiläinen, K. H.; Pouta, A.; Ridderstråle, M.; Rotter, J. I.; Sambrook, J. G.; Sanders, A. R.; Schmidt, C. Oliver; Sinisalo, J.; Smit, J. H.; Stringham, H. M.; Widen, E.; Wild, S. H.; Willemsen, G.; Zagato, L.; Zgaga, L.; Zitting, P.; Alavere, H.; Farrall, M.; McArdle, W. L.; Nelis, M.; Peters, M. J.; Ripatti, S.; van Meurs, J. B.; Aben, K. K.; Ardlie, K. G.; Beckmann, J. S.; Beilby, J. P.; Bergman, R. N.; Bergmann, S.; Collins, F. S.; Cusi, D.; den Heijer, M.; Eiriksdottir, G.; Gejman, P. V.; Hamsten, A.; Huikuri, H. V.; Iribarren, C.; Kähönen, M.; Kaprio, J.; Kathiresan, S.; Kiemeney, L.; Kocher, T.; Launer, L. J.; Lehtimäki, T.; Melander, O.; Mosley, T. H.; Musk, A. W.; Nieminen, M. S.; O'Donnell, C. J.; Ohlsson, C.; Oostra, B.; Palmer, L. J.; Raitakari, O.; Ridker, P. M.; Rioux, J. D.; Rissanen, A.; Rivolta, C.; Schunkert, H.; Shuldiner, A. R.; Siscovick, D. S.; Stumvoll, M.; Tönjes, A.; Tuomilehto, J.; van Ommen, G. J.; Viikari, J.; Heath, A. C.; Martin, N. G.; Montgomery, G. W.; Province, M. A.; Kayser, M.; Arnold, A. M.; Atwood, L. D.; Boerwinkle, E.; Chanock, S. J.; Deloukas, P.; Gieger, C.; Grönberg, H.; Hall, P.; Hattersley, A. T.; Hengstenberg, C.; Hoffman, W.; Lathrop, G. Mark; Salomaa, V.; Schreiber, S.; Uda, M.; Waterworth, D.; Wright, A. F.; Assimes, T. L.; Barroso, I.; Hofman, A.; Mohlke, K. L.; Boomsma, D. I.; Caulfield, M. J.; Cupples, L. Adrienne; Erdmann, J.; Fox, C. S.; Gudnason, V.; Gyllensten, U.; Harris, T. B.; Hayes, R. B.; Jarvelin, M. R.; Mooser, V.; Munroe, P. B.; Ouwehand, W. H.; Penninx, B. W.; Pramstaller, P. P.; Quertermous, T.; Rudan, I.; Samani, N. J.; Spector, T. D.; Völzke, H.; Watkins, H.; Wilson, J. F.; Groop, L. C.; Haritunians, T.; Hu, F. B.; Kaplan, R. C.; Metspalu, A.; North, K. E.; Schlessinger, D.; Wareham, N. J.; Hunter, D. J.; O'Connell, J. R.; Strachan, D. P.; Wichmann, H. E.; Borecki, I. B.; van Duijn, C. M.; Schadt, E. E.; Thorsteinsdottir, U.; Peltonen, L.; Uitterlinden, A. G.; Visscher, P. M.; Chatterjee, N.; Loos, R. J.; Boehnke, M.; McCarthy, M. I.; Ingelsson, E.; Lindgren, C. M.; Abecasis, G. R.; Stefansson, K.; Frayling, T. M.; Hirschhorn, J. N.; Teslovich, T. M.; Musunuru, K.; Smith, A. V.; Edmondson, A. C.; Stylianou, I. M.; Koseki, M.; Pirruccello, J. P.; Johansen, C. T.; Fouchier, S. W.; Isaacs, A.; Peloso, G. M.; Barbalic, M.; Ricketts, S. L.; Bis, J. C.; Chambers, J.; Orho-Melander, M.; Li, X.; Guo, X.; Li, M.; Cho, Y. Shin; Go, M. Jin; Kim, Y. Jin; Lee, J. Y.; Park, T.; Kim, K.; Sim, X.; Ong, R. Twee-Hee; Croteau-Chonka, D. C.; Lange, L. A.; Smith, J. D.; Song, K.; Yuan, X.; Lamina, C.; Zhang, W.; Zee, R. Y.; Witteman, J. C.; Whitfield, J. B.; Waterworth, D. M.; Waeber, G.; Vollenweider, P.; Tanaka, T.; Silander, K.; Sijbrands, E. J.; Scuteri, A.; Scott, J.; Salomaa, J.; Sabatti, C.; Ruokonen, A.; Rose, L. M.; Roberts, R.; Rieder, M.; Psaty, B. M.; Pedersen, N. L.; Pattaro, C.; Pare, G.; Oostra, B. A.; Nickerson, D. A.; McPherson, R.; McArdle, W.; Masson, D.; Marroni, F.; Magnusson, P. K.; Lucas, G.; Luben, R.; Langenberg, C.; Lakatta, E. G.; Laaksonen, R.; Kyvik, K. O.; Kronenberg, F.; Khaw, K. T.; Janssens, A. C.; Hovingh, G. Kees; Hastie, N. D.; Hall, A. S.; Guiducci, C.; Gonzalez, E.; Gieger, N. B.; Ferrucci, L.; Ejebe, K. G.; Döring, A.; Dominiczak, A. F.; Demissie, S.; de Geus, E. J.; de Faire, U.; Crawford, G.; Chen, Y. D.; Burtt, N. P.; Bonnycastle, L. L.; Boekholdt, S. M.; Bandinelli, S.; Ballantyne, C. M.; Ballantyne, T. L.; Altshuler, D.; Seielstad, M.; Wong, T. Y.; Tai, E. S.; Feranil, A. B.; Kuzawa, C. W.; Adair, L. S.; Taylor, H. A.; Gabriel, S. B.; Wilson, J. G.; Holm, H.; Krauss, R. M.; Ordovas, J. M.; Kooner, J. S.; Tall, A. R.; Hegele, R. A.; Kastelein, J. J.; Reilly, M. P.; Cupples, L. A.; Sandhu, M. S.; Rader, D. J.; Hernaez, Ruben; Kim, Lauren J.; Palmer, Cameron D.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E.; Launer, Lenore J.; Nalls, Michael A.; Clark, Jeanne M.; Mitchell, Braxton D.; Shuldiner, Alan R.; Butler, Johannah L.; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M.; Sahani, Dushyant V.; Salomaa, Veikko; Schwartz, Stephen M.; Siscovick, David S.; Carr, J. Jeffrey; Feitosa, Mary F.; Smith, Albert V.; Kao, W. H. Linda; Hirschhorn, Joel N.; Ehret, Georg B.; Rice, Kenneth M.; Bochud, Murielle; Johnson, Andrew D.; Chasman, Daniel I.; Tobin, Martin D.; Verwoert, Germaine C.; Pihur, Vasyl; Bragg-Gresham, Jennifer L.; Teumer, Alexander; Glazer, Nicole L.; Launer, Lenore; Zhao, Jing Hua; Aulchenko, Yurii; Sober, Siim; Parsa, Afshin; Arora, Pankaj; Dehghan, Abbas; Zhang, Feng; Lucas, Gavin; Hicks, Andrew A.; Tanaka, Toshiko; Wild, Sarah H.; Igl, Wilmar; Milaneschi, Yuri; Parker, Alex N.; Fava, Cristiano; Fox, Ervin R.; Kumari, Meena; Go, Min Jin; Kao, Wen Hong Linda; Sjogren, Marketa; Vinay, D. G.; Alexander, Myriam; Tabara, Yasuharu; Shaw-Hawkins, Sue; Whincup, Peter H.; Liu, Yongmei; Shi, Gang; Tayo, Bamidele; Seielstad, Mark; Sim, Xueling; Nguyen, Khanh-Dung Hoang; Lehtimaki, Terho; Matullo, Giuseppe; Wu, Ying; Gaunt, Tom R.; Onland-Moret, N. Charlotte; Cooper, Matthew N.; Platou, Carl G. P.; Org, Elin; Hardy, Rebecca; Dahgam, Santosh; Palmen, Jutta; Vitart, Veronique; Braund, Peter S.; Kuznetsova, Tatiana; Uiterwaal, Cuno S. P. M.; Adeyemo, Adebowale; Palmas, Walter; Ludwig, Barbara; Tomaszewski, Maciej; Tzoulaki, Ioanna; Palmer, Nicholette D.; Aspelund, Thor; Garcia, Melissa; Chang, Yen-Pei C.; O'Connell, Jeffrey R.; Steinle, Nanette I.; Grobbee, Diederick E.; Arking, Dan E.; Kardia, Sharon L.; Morrison, Alanna C.; Hernandez, Dena; Najjar, Samer; McArdle, Wendy L.; Hadley, David; Connell, John M.; Hingorani, Aroon D.; Day, Ian N. M.; Lawlor, Debbie A.; Beilby, John P.; Lawrence, Robert W.; Clarke, Robert; Collins, Rory; Hopewell, Jemma C.; Ongen, Halit; Dreisbach, Albert W.; Li, Yali; Young, J. H.; Bis, Joshua C.; Kahonen, Mika; Viikari, Jorma; Adair, Linda S.; Lee, Nanette R.; Chen, Ming-Huei; Olden, Matthias; Pattaro, Cristian; Bolton, Judith A. Hoffman; Kottgen, Anna; Bergmann, Sven; Chaturvedi, Nish R.; Islam, Muhammad; Jafar, Tazeen H.; Erdmann, Jeanette; Kulkarni, Smita R.; Bornstein, Stefan R.; Grassler, Jurgen; Kettunen, Johannes; Howard, Philip; Taylor, Andrew; Guarrera, Simonetta; Ricceri, Fulvio; Emilsson, Valur; Plump, Andrew; Barroso, Ines; Khaw, Kay-Tee; Weder, Alan B.; Hunt, Steven C.; Sun, Yan V.; Peltonen, Leena; Perola, Markus; Vartiainen, Erkki; Brand, Stefan-Martin; Staessen, Jan A.; Wang, Thomas J.; Burton, Paul R.; Artigas, Maria Soler; Dong, Yanbin; Wang, Xiaoling; Zhu, Haidong; Lohman, Kurt K.; Rudock, Megan E.; Heckbert, Susan R.; Smith, Nicholas L.; Wiggins, Kerri L.; Doumatey, Ayo; Shriner, Daniel; Veldre, Gudrun; Viigimaa, Margus; Kinra, Sanjay; Prabhakaran, Dorairajan; Tripathy, Vikal; Langefeld, Carl D.; Rosengren, Annika; Thelle, Dag S.; Corsi, Anna Maria; Singleton, Andrew; Forrester, Terrence; Hilton, Gina; McKenzie, Colin A.; Salako, Tunde; Iwai, Naoharu; Kita, Yoshikuni; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ueshima, Hirotsugu; Umemura, Satoshi; Eyheramendy, Susana; Cho, Yoon Shin; Kim, Hyung-Lae; Lee, Jong-Young; Sehmi, Joban S.; Hedblad, Bo; Smith, George Davey; Wong, Andrew; Stančakova, Alena; Raffel, Leslie J.; Yao, Jie; Kathiresan, Sekar; O'Donnell, Chris; Schwartz, Steven M.; Ikram, M. Arfan; Longstreth, Will T.; Mosley, Thomas H.; Seshadri, Sudha; Shrine, Nick R. G.; Wain, Louise V.; Laitinen, Jaana; Zitting, Paavo; Cooper, Jackie A.; Humphries, Steve E.; Danesh, John; Rasheed, Asif; Goel, Anuj; Hamsten, Anders; Bakker, Stephan J. L.; van Gilst, Wiek H.; Janipalli, Charles S.; Mani, K. Radha; Yajnik, Chittaranjan S.; Mattace-Raso, Francesco U. S.; Oostra, Ben A.; Demirkan, Ayse; Isaacs, Aaron; Rivadeneira, Fernando; Lakatta, Edward G.; Orru, Marco; Scuteri, Angelo; Lyytikainen, Leo-Pekka; Wurz, Peter; Ong, Rick Twee-Hee; Dorr, Marcus; Kroemer, Heyo K.; Volker, Uwe; Volzke, Henry; Galan, Pilar; Hercberg, Serge; Zelenika, Diana; Deloukas, Panos; Mangino, Massimo; Spector, Tim D.; Zhai, Guangju; Meschia, James F.; Sharma, Pankaj; Terzic, Janos; Kumar, M. J. Kranthi; Denniff, Matthew; Zukowska-Szczechowska, Ewa; Wagenknecht, Lynne E.; Fowkes, F. Gerald R.; Charchar, Fadi J.; Schwarz, Peter E. H.; Hayward, Caroline; Guo, Xiuqing; Rotimi, Charles; Bots, Michiel L.; Brand, Eva; Samani, Nilesh J.; Polasek, Ozren; Talmud, Philippa J.; Nyberg, Fredrik; Kuh, Diana; Laan, Maris; Palmer, Lyle J.; van der Schouw, Yvonne T.; Casas, Juan P.; Vineis, Paolo; Raitakari, Olli; Ganesh, Santhi K.; Wong, Tien Y.; Tai, E. Shyong; Cooper, Richard S.; Rao, Dabeeru C.; Morris, Richard W.; Dominiczak, Anna F.; Kivimaki, Mika; Marmot, Michael G.; Miki, Tetsuro; Saleheen, Danish; Chandak, Giriraj R.; Coresh, Josef; Navis, Gerjan; Han, Bok-Ghee; Zhu, Xiaofeng; Melander, Olle; Ridker, Paul M.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wright, Alan F.; Ferrucci, Luigi; Elosua, Roberto; Soranzo, Nicole; Sijbrands, Eric J. G.; Meneton, Pierre; Rotter, Jerome I.; Rettig, Rainer; Strachan, David P.; Beckmann, Jacques S.; Larson, Martin G.; Jarvelin, Marjo-Riitta; Psaty, Bruce M.; Chakravarti, Aravinda; Newton-Cheh, Christopher; Levy, Daniel; Caulfield, Mark J.; Dupuis, J.; Saxena, R.; Bouatia-Naji, N.; Gloyn, A. L.; Randall, J.; Rybin, D.; Henneman, P.; Grallert, H.; Dehghan, A.; Franklin, C. S.; Navarro, P.; Goel, A.; Egan, J. M.; Lajunen, T.; Grarup, N.; Sparsø, T.; Doney, A.; Kanoni, S.; Shrader, P.; Cavalcanti-Proença, C.; Kumari, M.; Timpson, N. J.; Zabena, C.; Rocheleau, G.; An, P.; O'Connell, J.; Elliott, A.; McCarroll, S. A.; Payne, F.; Roccasecca, R. M.; Pattou, F.; Sethupathy, P.; Ardlie, K.; Ariyurek, Y.; Balkau, B.; Barter, P.; Ben-Shlomo, Y.; Benediktsson, R.; Bennett, A. J.; Bochud, M.; Bonnefond, A.; Borch-Johnsen, K.; Böttcher, Y.; Brunner, E.; Bumpstead, S. J.; Charpentier, G.; Chines, P.; Clarke, R.; Coin, L. J.; Cornelis, M.; Crisponi, L.; Day, I. N.; Delplanque, J.; Dina, C.; Erdos, M. R.; Fedson, A. C.; Fischer-Rosinsky, A.; Forouhi, N. G.; Frants, R.; Franzosi, M. G.; Galan, P.; Goodarzi, M. O.; Graessler, J.; Groves, C. J.; Grundy, S.; Gwilliam, R.; Hadjadj, S.; Hallmans, G.; Hammond, N.; Han, X.; Hassanali, N.; Heath, S. C.; Hercberg, S.; Herder, C.; Hillman, D. R.; Hingorani, A. D.; Hung, J.; Isomaa, B.; Johnson, P. R.; Jørgensen, T.; Kaakinen, M.; Kesaniemi, Y. A.; Kivimaki, M.; Knight, B.; Lathrop, G. M.; Lawlor, D. A.; Le Bacquer, O.; Lecoeur, C.; Li, Y.; Lyssenko, V.; Mahley, R.; Manning, A. K.; Martínez-Larrad, M. T.; McAteer, J. B.; McCulloch, L. J.; Meisinger, C.; Melzer, D.; Meyre, D.; Mitchell, B. D.; Morken, M. A.; Mukherjee, S.; Naitza, S.; Narisu, N.; Neville, M. J.; Orrù, M.; Pakyz, R.; Palmer, C. N.; Paolisso, G.; Pearson, D.; Pfeiffer, A. F.; Posthuma, D.; Potter, S. C.; Rathmann, W.; Rice, K.; Roden, M.; Rolandsson, O.; Sandbaek, A.; Sandhu, M.; Sayer, A. A.; Scheet, P.; Scott, L. J.; Seedorf, U.; Sharp, S. J.; Shields, B.; Sigurethsson, G.; Silveira, A.; Simpson, L.; Singleton, A.; Smith, N. L.; Swift, A.; Syddall, H.; Syvänen, A. C.; Thorand, B.; Tichet, J.; Tuomi, T.; van Dijk, K. W.; van Hoek, M.; Varma, D.; Visvikis-Siest, S.; Vogelzangs, N.; Wagner, P. J.; Walley, A.; Walters, G. B.; Ward, K. L.; Yarnell, J. W.; Zeggini, E.; Zelenika, D.; Zethelius, B.; Zhai, G.; Zhao, J. H.; Meneton, P.; Nathan, D. M.; Williams, G. H.; Smith, G. D.; Bornstein, S. R.; Schwarz, P.; Spranger, J.; Karpe, F.; Cooper, C.; Dedoussis, G. V.; Serrano-Ríos, M.; Morris, A. D.; Lind, L.; Franks, P. W.; Ebrahim, S.; Marmot, M.; Kao, W. H.; Pankow, J. S.; Sampson, M. J.; Kuusisto, J.; Laakso, M.; Hansen, T.; Pedersen, O.; Buchanan, T. A.; Valle, T. T.; Kong, A.; Cao, A.; Sladek, R.; Froguel, P.; Watanabe, R. M.; Meigs, J. B.; Groop, L.; Florez, J. C.

    2011-01-01

    Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P =

  12. Genome-wide association analysis identifies six new loci associated with forced vital capacity

    Science.gov (United States)

    Loth, Daan W.; Artigas, María Soler; Gharib, Sina A.; Wain, Louise V.; Franceschini, Nora; Koch, Beate; Pottinger, Tess; Smith, Albert Vernon; Duan, Qing; Oldmeadow, Chris; Lee, Mi Kyeong; Strachan, David P.; James, Alan L.; Huffman, Jennifer E.; Vitart, Veronique; Ramasamy, Adaikalavan; Wareham, Nicholas J.; Kaprio, Jaakko; Wang, Xin-Qun; Trochet, Holly; Kähönen, Mika; Flexeder, Claudia; Albrecht, Eva; Lopez, Lorna M.; de Jong, Kim; Thyagarajan, Bharat; Alves, Alexessander Couto; Enroth, Stefan; Omenaas, Ernst; Joshi, Peter K.; Fall, Tove; Viňuela, Ana; Launer, Lenore J.; Loehr, Laura R.; Fornage, Myriam; Li, Guo; Wilk, Jemma B.; Tang, Wenbo; Manichaikul, Ani; Lahousse, Lies; Harris, Tamara B.; North, Kari E.; Rudnicka, Alicja R.; Hui, Jennie; Gu, Xiangjun; Lumley, Thomas; Wright, Alan F.; Hastie, Nicholas D.; Campbell, Susan; Kumar, Rajesh; Pin, Isabelle; Scott, Robert A.; Pietiläinen, Kirsi H.; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G.; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M.; Wojczynski, Mary; Pouta, Anneli; Johansson, Åsa; Wild, Sarah H.; Ingelsson, Erik; Rivadeneira, Fernando; Völzke, Henry; Hysi, Pirro G.; Eiriksdottir, Gudny; Morrison, Alanna C.; Rotter, Jerome I.; Gao, Wei; Postma, Dirkje S.; White, Wendy B.; Rich, Stephen S.; Hofman, Albert; Aspelund, Thor; Couper, David; Smith, Lewis J.; Psaty, Bruce M.; Lohman, Kurt; Burchard, Esteban G.; Uitterlinden, André G.; Garcia, Melissa; Joubert, Bonnie R.; McArdle, Wendy L.; Musk, A. Bill; Hansel, Nadia; Heckbert, Susan R.; Zgaga, Lina; van Meurs, Joyce B.J.; Navarro, Pau; Rudan, Igor; Oh, Yeon-Mok; Redline, Susan; Jarvis, Deborah; Zhao, Jing Hua; Rantanen, Taina; O’Connor, George T.; Ripatti, Samuli; Scott, Rodney J.; Karrasch, Stefan; Grallert, Harald; Gaddis, Nathan C.; Starr, John M.; Wijmenga, Cisca; Minster, Ryan L.; Lederer, David J.; Pekkanen, Juha; Gyllensten, Ulf; Campbell, Harry; Morris, Andrew P.; Gläser, Sven; Hammond, Christopher J.; Burkart, Kristin M.; Beilby, John; Kritchevsky, Stephen B.; Gudnason, Vilmundur; Hancock, Dana B.; Williams, O. Dale; Polasek, Ozren; Zemunik, Tatijana; Kolcic, Ivana; Petrini, Marcy F.; Wjst, Matthias; Kim, Woo Jin; Porteous, David J.; Scotland, Generation; Smith, Blair H.; Viljanen, Anne; Heliövaara, Markku; Attia, John R.; Sayers, Ian; Hampel, Regina; Gieger, Christian; Deary, Ian J.; Boezen, H. Marike; Newman, Anne; Jarvelin, Marjo-Riitta; Wilson, James F.; Lind, Lars; Stricker, Bruno H.; Teumer, Alexander; Spector, Timothy D.; Melén, Erik; Peters, Marjolein J.; Lange, Leslie A.; Barr, R. Graham; Bracke, Ken R.; Verhamme, Fien M.; Sung, Joohon; Hiemstra, Pieter S.; Cassano, Patricia A.; Sood, Akshay; Hayward, Caroline; Dupuis, Josée; Hall, Ian P.; Brusselle, Guy G.; Tobin, Martin D.; London, Stephanie J.

    2014-01-01

    Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR-129-2/HSD17B12, PRDM11, WWOX, and KCNJ2. Two (GSTCD and PTCH1) loci previously associated with spirometric measures were related to FVC. Newly implicated regions were followed-up in samples of African American, Korean, Chinese, and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and pathogenesis of restrictive lung disease. PMID:24929828

  13. Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension

    NARCIS (Netherlands)

    Padmanabhan, Sandosh; Melander, Olle; Johnson, Toby; Di Blasio, Anna Maria; Lee, Wai K.; Gentilini, Davide; Hastie, Claire E.; Menni, Cristina; Monti, Maria Cristina; Delles, Christian; Laing, Stewart; Corso, Barbara; Navis, Gerjan; Kwakernaak, Arjan J.; van der Harst, Pim; Bochud, Murielle; Maillard, Marc; Burnier, Michel; Hedner, Thomas; Kjeldsen, Sverre; Wahlstrand, Bjorn; Sjogren, Marketa; Fava, Cristiano; Montagnana, Martina; Danese, Elisa; Torffvit, Ole; Hedblad, Bo; Snieder, Harold; Connell, John M. C.; Brown, Morris; Samani, Nilesh J.; Farrall, Martin; Cesana, Giancarlo; Mancia, Giuseppe; Signorini, Stefano; Grassi, Guido; Eyheramendy, Susana; Wichmann, H. Erich; Laan, Maris; Strachan, David P.; Sever, Peter; Shields, Denis Colm; Stanton, Alice; Vollenweider, Peter; Teumer, Alexander; Voelzke, Henry; Rettig, Rainer; Newton-Cheh, Christopher; Arora, Pankaj; Zhang, Feng; Soranzo, Nicole; Spector, Timothy D.; Lucas, Gavin; Kathiresan, Sekar; Siscovick, David S.; Luan, Jian'an; Loos, Ruth J. F.; Wareham, Nicholas J.; Penninx, Brenda W.; Nolte, Ilja M.; McBride, Martin; Miller, William H.; Nicklin, Stuart A.; Baker, Andrew H.; Graham, Delyth; McDonald, Robert A.; Pell, Jill P.; Sattar, Naveed; Welsh, Paul; Munroe, Patricia; Caulfield, Mark J.; Zanchetti, Alberto; Dominiczak, Anna F.

    2010-01-01

    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

  14. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

    NARCIS (Netherlands)

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted

  15. Genome-wide association study identifies eight loci associated with blood pressure

    NARCIS (Netherlands)

    Newton-Cheh, Christopher; Johnson, Toby; Gateva, Vesela; Tobin, Martin D.; Bochud, Murielle; Coin, Lachlan; Najjar, Samer S.; Zhao, Jing Hua; Heath, Simon C.; Eyheramendy, Susana; Papadakis, Konstantinos; Voight, Benjamin F.; Scott, Laura J.; Zhang, Feng; Farrall, Martin; Tanaka, Toshiko; Wallace, Chris; Chambers, John C.; Khaw, Kay-Tee; Nilsson, Peter; van der Harst, Pim; Polidoro, Silvia; Grobbee, Diederick E.; Onland-Moret, N. Charlotte; Bots, Michiel L.; Wain, Louise V.; Elliott, Katherine S.; Teumer, Alexander; Luan, Jian'an; Lucas, Gavin; Kuusisto, Johanna; Burton, Paul R.; Hadley, David; McArdle, Wendy L.; Brown, Morris; Dominiczak, Anna; Newhouse, Stephen J.; Samani, Nilesh J.; Webster, John; Zeggini, Eleftheria; Beckmann, Jacques S.; Bergmann, Sven; Lim, Noha; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M.; Yuan, Xin; Groop, Leif; Orho-Melander, Marju; Allione, Alessandra; Di Gregorio, Alessandra; Guarrera, Simonetta; Panico, Salvatore; Ricceri, Fulvio; Romanazzi, Valeria; Sacerdote, Carlotta; Vineis, Paolo; Barroso, Ines; Sandhu, Manjinder S.; Luben, Robert N.; Crawford, Gabriel J.; Jousilahti, Pekka; Perola, Markus; Boehnke, Michael; Bonnycastle, Lori L.; Collins, Francis S.; Jackson, Anne U.; Mohlke, Karen L.; Stringham, Heather M.; Valle, Timo T.; Willer, Cristen J.; Bergman, Richard N.; Morken, Mario A.; Doering, Angela; Gieger, Christian; Illig, Thomas; Meitinger, Thomas; Org, Elin; Pfeufer, Arne; Wichmann, H. Erich; Kathiresan, Sekar; Marrugat, Jaume; O'Donnell, Christopher J.; Schwartz, Stephen M.; Siscovick, David S.; Subirana, Isaac; Freimer, Nelson B.; Hartikainen, Anna-Liisa; McCarthy, Mark I.; O'Reilly, Paul F.; Peltonen, Leena; Pouta, Anneli; de Jong, Paul E.; Snieder, Harold; van Gilst, Wiek H.; Clarke, Robert; Goel, Anuj; Hamsten, Anders; Peden, John F.; Seedorf, Udo; Syvanen, Ann-Christine; Tognoni, Giovanni; Lakatta, Edward G.; Sanna, Serena; Scheet, Paul; Schlessinger, David; Scuteri, Angelo; Doerr, Marcus; Ernst, Florian; Felix, Stephan B.; Homuth, Georg; Lorbeer, Roberto; Reffelmann, Thorsten; Rettig, Rainer; Voelker, Uwe; Galan, Pilar; Gut, Ivo G.; Hercberg, Serge; Lathrop, G. Mark; Zelenika, Diana; Deloukas, Panos; Soranzo, Nicole; Williams, Frances M.; Zhai, Guangju; Salomaa, Veikko; Laakso, Markku; Elosua, Roberto; Forouhi, Nita G.; Volzke, Henry; Uiterwaal, Cuno S.; van der Schouw, Yvonne T.; Numans, Mattijs E.; Matullo, Giuseppe; Navis, Gerjan; Berglund, Goran; Bingham, Sheila A.; Kooner, Jaspal S.; Connell, John M.; Bandinelli, Stefania; Ferrucci, Luigi; Watkins, Hugh; Spector, Tim D.; Tuomilehto, Jaakko; Altshuler, David; Strachan, David P.; Laan, Maris; Meneton, Pierre; Wareham, Nicholas J.; Uda, Manuela; Jarvelin, Marjo-Riitta; Mooser, Vincent; Melander, Olle; Loos, Ruth J. F.; Elliott, Paul; Abecasis, Goncalo R.; Caulfield, Mark; Munroe, Patricia B.

    Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure

  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. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    A. Okbay (Aysu); J.P. Beauchamp (Jonathan); Fontana, M.A. (Mark Alan); J.J. Lee (James J.); T.H. Pers (Tune); Rietveld, C.A. (Cornelius A.); P. Turley (Patrick); Chen, G.-B. (Guo-Bo); V. Emilsson (Valur); Meddens, S.F.W. (S. Fleur W.); Oskarsson, S. (Sven); Pickrell, J.K. (Joseph K.); Thom, K. (Kevin); Timshel, P. (Pascal); R. de Vlaming (Ronald); A. Abdellaoui (Abdel); T.S. Ahluwalia (Tarunveer Singh); J. Bacelis (Jonas); C. Baumbach (Clemens); Bjornsdottir, G. (Gyda); J.H. Brandsma (Johan); Pina Concas, M. (Maria); J. Derringer; Furlotte, N.A. (Nicholas A.); T.E. Galesloot (Tessel); S. Girotto; Gupta, R. (Richa); L.M. Hall (Leanne M.); S.E. Harris (Sarah); E. Hofer; Horikoshi, M. (Momoko); J.E. Huffman (Jennifer E.); Kaasik, K. (Kadri); I.-P. Kalafati (Ioanna-Panagiota); R. Karlsson (Robert); A. Kong (Augustine); J. Lahti (Jari); S.J. van der Lee (Sven); Deleeuw, C. (Christiaan); P.A. Lind (Penelope); Lindgren, K.-O. (Karl-Oskar); Liu, T. (Tian); M. Mangino (Massimo); J. Marten (Jonathan); E. Mihailov (Evelin); M. Miller (Mike); P.J. van der Most (Peter); C. Oldmeadow (Christopher); A. Payton (Antony); N. Pervjakova (Natalia); W.J. Peyrot (Wouter ); Qian, Y. (Yong); O. Raitakari (Olli); Rueedi, R. (Rico); Salvi, E. (Erika); Schmidt, B. (Börge); Schraut, K.E. (Katharina E.); Shi, J. (Jianxin); A.V. Smith (Albert Vernon); R.A. Poot (Raymond); B. St Pourcain (Beate); A. Teumer (Alexander); G. Thorleifsson (Gudmar); N. Verweij (Niek); D. Vuckovic (Dragana); Wellmann, J. (Juergen); H.J. Westra (Harm-Jan); Yang, J. (Jingyun); Zhao, W. (Wei); Zhu, Z. (Zhihong); B.Z. Alizadeh (Behrooz); N. Amin (Najaf); Bakshi, A. (Andrew); S.E. Baumeister (Sebastian); G. Biino (Ginevra); K. Bønnelykke (Klaus); P.A. Boyle (Patricia); H. Campbell (Harry); Cappuccio, F.P. (Francesco P.); G. Davies (Gail); J.E. de Neve (Jan-Emmanuel); P. Deloukas (Panagiotis); I. Demuth (Ilja); Ding, J. (Jun); Eibich, P. (Peter); Eisele, L. (Lewin); N. Eklund (Niina); D.M. Evans (David); J.D. Faul (Jessica D.); M.F. Feitosa (Mary Furlan); A.J. Forstner (Andreas); I. Gandin (Ilaria); Gunnarsson, B. (Bjarni); B.V. Halldorsson (Bjarni); T.B. Harris (Tamara); E.G. Holliday (Elizabeth); A.C. Heath (Andrew C.); L.J. Hocking; G. Homuth (Georg); M. Horan (Mike); J.J. Hottenga (Jouke Jan); P.L. de Jager (Philip); P.K. Joshi (Peter); A. Juqessur (Astanand); M. Kaakinen (Marika); M. Kähönen (Mika); S. Kanoni (Stavroula); Keltigangas-Järvinen, L. (Liisa); L.A.L.M. Kiemeney (Bart); I. Kolcic (Ivana); Koskinen, S. (Seppo); A. Kraja (Aldi); Kroh, M. (Martin); Z. Kutalik (Zoltán); A. Latvala (Antti); L.J. Launer (Lenore); Lebreton, M.P. (Maël P.); D.F. Levinson (Douglas F.); P. Lichtenstein (Paul); P. Lichtner (Peter); D.C. Liewald (David C.); A. Loukola (Anu); P.A. Madden (Pamela); R. Mägi (Reedik); Mäki-Opas, T. (Tomi); R.E. Marioni (Riccardo); P. Marques-Vidal; Meddens, G.A. (Gerardus A.); G. Mcmahon (George); C. Meisinger (Christa); T. Meitinger (Thomas); Milaneschi, Y. (Yusplitri); L. Milani (Lili); G.W. Montgomery (Grant); R. Myhre (Ronny); C.P. Nelson (Christopher P.); D.R. Nyholt (Dale); W.E.R. Ollier (William); A. Palotie (Aarno); L. Paternoster (Lavinia); N.L. Pedersen (Nancy); K. Petrovic (Katja); D.J. Porteous (David J.); K. Räikkönen (Katri); Ring, S.M. (Susan M.); A. Robino (Antonietta); O. Rostapshova (Olga); I. Rudan (Igor); A. Rustichini (Aldo); V. Salomaa (Veikko); Sanders, A.R. (Alan R.); A.-P. Sarin; R. Schmidt (Reinhold); R.J. Scott (Rodney); B.H. Smith (Blair); J.A. Smith (Jennifer A); J.A. Staessen (Jan); E. Steinhagen-Thiessen (Elisabeth); K. Strauch (Konstantin); A. Terracciano; M.D. Tobin (Martin); S. Ulivi (Shelia); S. Vaccargiu (Simona); L. Quaye (Lydia); F.J.A. van Rooij (Frank); C. Venturini (Cristina); A.A.E. Vinkhuyzen (Anna A.); U. Völker (Uwe); Völzke, H. (Henry); J.M. Vonk (Judith); D. Vozzi (Diego); J. Waage (Johannes); E.B. Ware (Erin B.); G.A.H.M. Willemsen (Gonneke); J. Attia (John); D.A. Bennett (David A.); Berger, K. (Klaus); L. Bertram (Lars); H. Bisgaard (Hans); D.I. Boomsma (Dorret); I.B. Borecki (Ingrid); U. Bültmann (Ute); C.F. Chabris (Christopher F.); F. Cucca (Francesco); D. Cusi (Daniele); I.J. Deary (Ian J.); G.V. Dedoussis (George); C.M. van Duijn (Cornelia); K. Hagen (Knut); B. Franke (Barbara); L. Franke (Lude); P. Gasparini (Paolo); P.V. Gejman (Pablo); C. Gieger (Christian); H.J. Grabe (Hans Jörgen); J. Gratten (Jacob); P.J.F. Groenen (Patrick); V. Gudnason (Vilmundur); P. van der Harst (Pim); C. Hayward (Caroline); D.A. Hinds (David A.); W. Hoffmann (Wolfgang); E. Hypponen (Elina); W.G. Iacono (William); B. Jacobsson (Bo); M.-R. Jarvelin (Marjo-Riitta); K.-H. JöCkel (Karl-Heinz); J. Kaprio (Jaakko); S.L.R. Kardia (Sharon); T. Lehtimäki (Terho); Lehrer, S.F. (Steven F.); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); A. Metspalu (Andres); N. Pendleton (Neil); B.W.J.H. Penninx (Brenda); M. Perola (Markus); N. Pirastu (Nicola); M. Pirastu (Mario); O. Polasek (Ozren); D. Posthuma (Danielle); C. Power (Christopher); M.A. Province (Mike); N.J. Samani (Nilesh); Schlessinger, D. (David); R. Schmidt (Reinhold); T.I.A. Sørensen (Thorkild); T.D. Spector (Timothy); J-A. Zwart (John-Anker); U. Thorsteinsdottir (Unnur); A.R. Thurik (Roy); Timpson, N.J. (Nicholas J.); H.W. Tiemeier (Henning); J.Y. Tung (Joyce Y.); A.G. Uitterlinden (André); Vitart, V. (Veronique); P. Vollenweider (Peter); D.R. Weir (David); J.F. Wilson (James F.); A.F. Wright (Alan); Conley, D.C. (Dalton C.); R.F. Krueger; G.D. Smith; Hofman, A. (Albert); D. Laibson (David); S.E. Medland (Sarah Elizabeth); M.N. Meyer (Michelle N.); J. Yang (Joanna); M. Johannesson (Magnus); P.M. Visscher (Peter); T. Esko (Tõnu); Ph.D. Koellinger (Philipp); D. Cesarini (David); D.J. Benjamin (Daniel J.)

    2016-01-01

    textabstractEducational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that

  18. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Brge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bonnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldorsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kahonen, Mika; Kanoni, Stavroula; Keltigangas-Jarvinen, Liisa; Kiemeney, Lambertus A. L. M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Mael P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C. M.; Loukola, Anu; Madden, Pamela A.; Magi, Reedik; Maki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E. R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Raikkonen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J. A.; Venturini, Cristina; Vinkhuyzen, Anna A. E.; Volker, Uwe; Volzke, Henry; Vonk, Judith M.; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jorgen; Gratten, Jacob; Groenen, Patrick J. F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppnen, Elina; Iacono, William G.; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Jockel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Lehtimaki, Terho; Lehrer, Steven F.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W. J. H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sorensen, Thorkild I. A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, Andre G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tonu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  19. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, ...

  20. Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region

    NARCIS (Netherlands)

    Skibola, Christine F.; Berndt, Sonja I.; Vijai, Joseph; Conde, Lucia; Wang, Zhaoming; Yeager, Meredith; de Bakker, Paul I. W.; Birmann, Brenda M.; Vajdic, Claire M.; Foo, Jia-Nee; Bracci, Paige M.; Vermeulen, Roel C. H.|info:eu-repo/dai/nl/216532620; Slager, Susan L.; de Sanjose, Silvia; Wang, Sophia S.; Linet, Martha S.; Salles, Gilles; Lan, Qing; Severi, Gianluca; Hjalgrim, Henrik; Lightfoot, Tracy; Melbye, Mads; Gu, Jian; Ghesquieres, Herve; Link, Brian K.; Morton, Lindsay M.; Holly, Elizabeth A.; Smith, Alex; Tinker, Lesley F.; Teras, Lauren R.; Kricker, Anne; Becker, Nikolaus; Purdue, Mark P.; Spinelli, John J.; Zhang, Yawei; Giles, Graham G.; Vineis, Paolo; Monnereau, Alain; Bertrand, Kimberly A.; Albanes, Demetrius; Zeleniuch-Jacquotte, Anne; Gabbas, Attilio; Chung, Charles C.; Burdett, Laurie; Hutchinson, Amy; Lawrence, Charles; Montalvan, Rebecca; Liang, Liming; Huang, Jinyan; Ma, Baoshan; Liu, Jianjun; Adami, Hans-Olov; Glimelius, Bengt; Ye, Yuanqing; Nowakowski, Grzegorz S.; Dogan, Ahmet; Thompson, Carrie A.; Habermann, Thomas M.; Novak, Anne J.; Liebow, Mark; Witzig, Thomas E.; Weiner, George J.; Schenk, Maryjean; Hartge, Patricia; De Roos, Anneclaire J.; Cozen, Wendy; Zhi, Degui; Akers, Nicholas K.; Riby, Jacques; Smith, Martyn T.; Lacher, Mortimer; Villano, Danylo J.; Maria, Ann; Roman, Eve; Kane, Eleanor; Jackson, Rebecca D.; North, Kari E.; Diver, W. Ryan; Turner, Jenny; Armstrong, Bruce K.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; McKay, James; Brooks-Wilson, Angela R.; Zheng, Tongzhang; Holford, Theodore R.; Chamosa, Saioa; Kaaks, Rudolph; Kelly, Rachel S.; Ohlsson, Bodil; Travis, Ruth C.; Weiderpass, Elisabete; Clave, Jacqueline; Giovannucci, Edward; Kraft, Peter; Virtamo, Jarmo; Mazza, Patrizio; Cocco, Pierluigi; Ennas, Maria Grazia; Chiu, Brian C. H.; Fraumeni, Joseph R.; Nieters, Alexandra; Offit, Kenneth; Wu, Xifeng; Cerhan, James R.; Smedby, Karin E.; Chanock, Stephen J.; Rothman, Nathaniel

    2014-01-01

    Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European

  1. Molecular markers for tolerance of European ash (Fraxinus excelsior) to dieback disease identified using Associative Transcriptomics

    DEFF Research Database (Denmark)

    Harper, Andrea L.; McKinney, Lea Vig; Nielsen, Lene Rostgaard

    2016-01-01

    panel scored for disease symptoms and identified markers strongly associated with canopy damage in infected trees. Using these markers we predicted phenotypes in a test panel of unrelated trees, successfully identifying individuals with a low level of susceptibility to the disease. Co...

  2. Genome-Wide Association Study Identifies Four Loci Associated with Eruption of Permanent Teeth

    Science.gov (United States)

    Zhang, Hao; Shaffer, John R.; Hansen, Thomas; Esserlind, Ann-Louise; Boyd, Heather A.; Nohr, Ellen A.; Timpson, Nicholas J.; Fatemifar, Ghazaleh; Paternoster, Lavinia; Evans, David M.; Weyant, Robert J.; Levy, Steven M.; Lathrop, Mark; Smith, George Davey; Murray, Jeffrey C.; Olesen, Jes; Werge, Thomas; Marazita, Mary L.; Sørensen, Thorkild I. A.; Melbye, Mads

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at Peruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9–4.1) fewer permanent teeth than children with 0 or 1 of these alleles. PMID:21931568

  3. Functional complementation studies identify candidate genes and common genetic variants associated with ovarian cancer survival

    DEFF Research Database (Denmark)

    Quaye, Lydia; Dafou, Dimitra; Ramus, Susan J

    2009-01-01

    Common germline genetic variation and/or somatic alterations in tumours may be associated with survival in women diagnosed with ovarian cancer. The successful identification of genetic associations relies on a suitable strategy for identifying and testing candidate genes. We used microcell-mediat...

  4. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    NARCIS (Netherlands)

    Voight, Benjamin F.; Scott, Laura J.; Steinthorsdottir, Valgerdur; Morris, Andrew P.; Dina, Christian; Welch, Ryan P.; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S.; Thorleifsson, Gudmar; McCulloch, Laura J.; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J.; Raychaudhuri, Soumya; McCarroll, Steve A.; Langenberg, Claudia; Hofmann, Oliver M.; Dupuis, Josee; Qi, Lu; Segre, Ayellet V.; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J.; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L.; Bostrom, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisel P.; Charpentier, Guillaume; Chines, Peter S.; Cornelis, Marilyn; Couper, David J.; Crawford, Gabe; Doney, Alex S. F.; Elliott, Katherine S.; Elliott, Amanda L.; Erdos, Michael R.; Fox, Caroline S.; Franklin, Christopher S.; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J.; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U.; Johnson, Paul R. V.; Jorgensen, Torben; Kao, Wen H. L.; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M.; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A.; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R.; Payne, Felicity; Perry, John R. B.; Petersen, Ann-Kristin; Platou, Carl; Proenca, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N. William; Robertson, Neil R.; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J.; Saxena, Richa; Shields, Beverley M.; Shrader, Peter; Sigurdsson, Gunnar; Sparso, Thomas; Strassburger, Klaus; Stringham, Heather M.; Sun, Qi; Swift, Amy J.; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M.; van Haeften, Timon W.; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V.; Walters, G. Bragi; Weedon, Michael N.; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N.; Cauchi, Stephane; Collins, Francis S.; Gloyn, Anna L.; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A.; Hitman, Graham A.; Hofman, Albert; Hunter, David J.; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L.; Morris, Andrew D.; Palmer, Colin N. A.; Pramstaller, Peter P.; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D.; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J.; Watanabe, Richard M.; Abecasis, Goncalo R.; Boehm, Bernhard O.; Campbell, Harry; Daly, Mark J.; Hattersley, Andrew T.; Hu, Frank B.; Meigs, James B.; Pankow, James S.; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Ines; Florez, Jose C.; Frayling, Timothy M.; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F.; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M.; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I.

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined

  5. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    NARCIS (Netherlands)

    B.F. Voight (Benjamin); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); R.P. Welch (Ryan); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); N. Amin (Najaf); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steven); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); A.V. Segrè (Ayellet); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); B. Balkau (Beverley); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); M.R. Erdos (Michael); C.S. Fox (Caroline); C.S. Franklin (Christopher); M. Ganser (Martha); C. Gieger (Christian); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C.J. Groves (Christopher); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); B. Isomaa (Bo); A.U. Jackson (Anne); P.R.V. Johnson (Paul); T. Jørgensen (Torben); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); N. Narisu (Narisu); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John); A.K. Petersen; C. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.W. Rayner (Nigel William); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); A.J. Swift (Amy); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G.B. Walters (Bragi); M.N. Weedon (Michael); C. Wijmenga (Cisca); J.C.M. Witteman (Jacqueline); R.N. Bergman (Richard); S. Cauchi (Stephane); F.S. Collins (Francis); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); A. Hofman (Albert); D. Hunter (David); K. Hveem (Kristian); M. Laakso (Markku); K.L. Mohlke (Karen); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); M. Walker (Mark); N.J. Wareham (Nick); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); H. Campbell (Harry); M.J. Daly (Mark); A.T. Hattersley (Andrew); F.B. Hu (Frank); J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); H.E. Wichmann (Erich); I. Barroso (Inês); J.C. Florez (Jose); T.M. Frayling (Timothy); L. Groop (Leif); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James); T. Illig (Thomas); P. Froguel (Philippe); P. Tikka-Kleemola (Päivi); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark); R.M. Watanabe (Richard)

    2010-01-01

    textabstractBy combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals

  6. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

    NARCIS (Netherlands)

    L.A. Lange (Leslie); Y. Hu (Youna); H. Zhang (He); C. Xue (Chenyi); E.M. Schmidt (Ellen); Z.-Z. Tang (Zheng-Zheng); C. Bizon (Chris); E.M. Lange (Ethan); G.D. Smith; E.H. Turner (Emily); Y. Jun (Yang); H.M. Kang (Hyun Min); G.M. Peloso (Gina); P. Auer (Paul); K.-P. Li (Kuo-Ping); J. Flannick (Jason); J. Zhang (Ji); C. Fuchsberger (Christian); K. Gaulton (Kyle); C.M. Lindgren (Cecilia); A. Locke (Adam); A.K. Manning (Alisa); X. Sim (Xueling); M.A. Rivas (Manuel); O.L. Holmen (Oddgeir); R.F. Gottesman (Rebecca); Y. Lu (Yingchang); D. Ruderfer (Douglas); E.A. Stahl (Eli); Q. Duan (Qing); Y. Li (Yun); P. Durda (Peter); S. Jiao (Shuo); A.J. Isaacs (Aaron); A. Hofman (Albert); J.C. Bis (Joshua); D.D. Correa; M.D. Griswold (Michael); M. Jakobsdottir (Margret); G.D. Smith; P.J. Schreiner (Pamela); M.F. Feitosa (Mary Furlan); Q. Zhang (Qunyuan); J.E. Huffman (Jennifer); S. Crosby; C.L. Wassel (Christina); R. Do (Ron); N. Franceschini (Nora); L.W. Martin (Lisa); J.G. Robinson (Jennifer); T.L. Assimes (Themistocles); D.R. Crosslin (David); E.A. Rosenthal (Elisabeth); M.Y. Tsai (Michael); M. Rieder (Mark); D.N. Farlow (Deborah); A.R. Folsom (Aaron); T. Lumley (Thomas); E.R. Fox (Ervin); C.S. Carlson (Christopher); U. Peters (Ulrike); R.D. Jackson (Rebecca); C.M. van Duijn (Cornelia); A.G. Uitterlinden (André); D. Levy (Daniel); J.I. Rotter (Jerome); H.A. Taylor (Herman); V. Gudnason (Vilmundur); D.S. Siscovick (David); M. Fornage (Myriam); I.B. Borecki (Ingrid); C. Hayward (Caroline); I. Rudan (Igor); Y.E. Chen (Y. Eugene); E.P. Bottinger (Erwin); R.J.F. Loos (Ruth); P. Sætrom (Pål); K. Hveem (Kristian); M. Boehnke (Michael); L. Groop (Leif); M.I. McCarthy (Mark); T. Meitinger (Thomas); C. Ballantyne (Christie); S.B. Gabriel (Stacey); C.J. O'Donnell (Christopher); W.S. Post (Wendy S.); K.E. North (Kari); A. Reiner (Alexander); E.A. Boerwinkle (Eric); B.M. Psaty (Bruce); D. Altshuler (David); S. Kathiresan (Sekar); D.Y. Lin (Dan); G.P. Jarvik (Gail); L.A. Cupples (Adrienne); C. Kooperberg (Charles); J.G. Wilson (James); D.A. Nickerson (Deborah); G.R. Abecasis (Gonçalo); S.S. Rich (Stephen); R.P. Tracy (Russell); C.J. Willer (Cristen)

    2014-01-01

    textabstractElevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency

  7. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna

    2013-01-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10...

  8. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

    NARCIS (Netherlands)

    Schunkert, Heribert; König, Inke R.; Kathiresan, Sekar; Reilly, Muredach P.; Assimes, Themistocles L.; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F. R.; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S.; Andersen, Karl; Anderson, Jeffrey L.; Ardissino, Diego; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Timothy A.; Becker, Diane M.; Becker, Lewis C.; Berger, Klaus; Bis, Joshua C.; Boekholdt, S. Matthijs; Boerwinkle, Eric; Braund, Peter S.; Brown, Morris J.; Burnett, Mary Susan; Buysschaert, Ian; Carlquist, John F.; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W.; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M.; Diemert, Patrick; Do, Ron; Doering, Angela; Eifert, Sandra; Mokhtari, Nour Eddine El; Ellis, Stephen G.; Elosua, Roberto; Engert, James C.; Epstein, Stephen E.; de Faire, Ulf; Fischer, Marcus; Folsom, Aaron R.; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R.; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L.; Hofman, Albert; Horne, Benjamin D.; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T.; Jukema, J. Wouter; Kaiser, Michael A.; Kaplan, Lee M.; Kastelein, John J. P.; Khaw, Kay-Tee; Knowles, Joshua W.; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Loley, Christina; Lotery, Andrew J.; Mannucci, Pier M.; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P.; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Merlini, Pier Angelica; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W.; Muhlestein, Joseph B.; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P.; Nöthen, Markus M.; Olivieri, Oliviero; Patel, Riyaz S.; Patterson, Chris C.; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A.; Rader, Daniel J.; Rallidis, Loukianos S.; Rice, Catherine; Rosendaal, Frits R.; Rubin, Diana; Salomaa, Veikko; Sampietro, M. Lourdes; Sandhu, Manj S.; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M.; Siscovick, David S.; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B.; Snoep, Jaapjan D.; Soranzo, Nicole; Spertus, John A.; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Tang, W. H. Wilson; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G.; van Rij, Andre M.; Voight, Benjamin F.; Wareham, Nick J.; Wells, George A.; Wichmann, H.-Erich; Wild, Philipp S.; Willenborg, Christina; Witteman, Jaqueline C. M.; Wright, Benjamin J.; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H.; Cupples, L. Adrienne; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H.; Hall, Alistair S.; Deloukas, Panos; Thompson, John R.; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O'Donnell, Christopher J.; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J.

    2011-01-01

    We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13

  9. Genome-wide association analysis identifies three new breast cancer susceptibility loci

    DEFF Research Database (Denmark)

    Ghoussaini, Maya; Fletcher, Olivia; Michailidou, Kyriaki

    2012-01-01

    Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ...

  10. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

    NARCIS (Netherlands)

    Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C; Cookson, William O C; Altmüller, Janine; Ang, Wei; Barr, R Graham; Beaty, Terri H; Becker, Allan B; Beilby, John; Bisgaard, Hans; Bjornsdottir, Unnur Steina; Bleecker, Eugene; Bønnelykke, Klaus; Boomsma, Dorret I; Bouzigon, Emmanuelle; Brightling, Christopher E; Brossard, Myriam; Brusselle, Guy G; Burchard, Esteban; Burkart, Kristin M; Bush, Andrew; Chan-Yeung, Moira; Chung, Kian Fan; Couto Alves, Alexessander; Curtin, John A; Custovic, Adnan; Daley, Denise; de Jongste, Johan C; Del-Rio-Navarro, Blanca E; Donohue, Kathleen M; Duijts, Liesbeth; Eng, Celeste; Eriksson, Johan G; Farrall, Martin; Fedorova, Yuliya; Feenstra, Bjarke; Ferreira, Manuel A; Freidin, Maxim B; Gajdos, Zofia; Gauderman, Jim; Gehring, Ulrike; Geller, Frank; Genuneit, Jon; Gharib, Sina A; Gilliland, Frank; Granell, Raquel; Graves, Penelope E; Gudbjartsson, Daniel F; Haahtela, Tari; Heckbert, Susan R; Heederik, Dick; Heinrich, Joachim; Heliövaara, Markku; Henderson, John; Himes, Blanca E; Hirose, Hiroshi; Hirschhorn, Joel N; Hofman, Albert; Holt, Patrick; Hottenga, Jouke; Hudson, Thomas J; Hui, Jennie; Imboden, Medea; Ivanov, Vladimir; Jaddoe, Vincent W V; James, Alan; Janson, Christer; Jarvelin, Marjo-Riitta; Jarvis, Deborah; Jones, Graham; Jonsdottir, Ingileif; Jousilahti, Pekka; Kabesch, Michael; Kähönen, Mika; Kantor, David B; Karunas, Alexandra S; Khusnutdinova, Elza; Koppelman, Gerard H; Kozyrskyj, Anita L; Kreiner, Eskil; Kubo, Michiaki; Kumar, Rajesh; Kumar, Ashish; Kuokkanen, Mikko; Lahousse, Lies; Laitinen, Tarja; Laprise, Catherine; Lathrop, Mark; Lau, Susanne; Lee, Young-Ae; Lehtimäki, Terho; Letort, Sébastien; Levin, Albert M; Li, Guo; Liang, Liming; Loehr, Laura R; London, Stephanie J; Loth, Daan W; Manichaikul, Ani; Marenholz, Ingo; Martinez, Fernando J; Matheson, Melanie C; Mathias, Rasika A; Matsumoto, Kenji; Mbarek, Hamdi; McArdle, Wendy L; Melbye, Mads; Melén, Erik; Meyers, Deborah; Michel, Sven; Mohamdi, Hamida; Musk, Arthur W; Myers, Rachel A; Nieuwenhuis, Maartje A E; Noguchi, Emiko; O'Connor, George T; Ogorodova, Ludmila M; Palmer, Cameron D; Palotie, Aarno; Park, Julie E; Pennell, Craig E; Pershagen, Göran; Polonikov, Alexey; Postma, Dirkje S; Probst-Hensch, Nicole; Puzyrev, Valery P; Raby, Benjamin A; Raitakari, Olli T; Ramasamy, Adaikalavan; Rich, Stephen S; Robertson, Colin F; Romieu, Isabelle; Salam, Muhammad T; Salomaa, Veikko; Schlünssen, Vivi; Scott, Robert; Selivanova, Polina A; Sigsgaard, Torben; Simpson, Angela; Siroux, Valérie; Smith, Lewis J; Solodilova, Maria; Standl, Marie; Stefansson, Kari; Strachan, David P; Stricker, Bruno H; Takahashi, Atsushi; Thompson, Philip J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tiesler, Carla M T; Torgerson, Dara G; Tsunoda, Tatsuhiko; Uitterlinden, André G; van der Valk, Ralf J P; Vaysse, Amaury; Vedantam, Sailaja; von Berg, Andrea; von Mutius, Erika; Vonk, Judith M; Waage, Johannes; Wareham, Nick J; Weiss, Scott T; White, Wendy B; Wickman, Magnus; Widén, Elisabeth; Willemsen, Gonneke; Williams, L Keoki; Wouters, Inge M; Yang, James J; Zhao, Jing Hua; Moffatt, Miriam F; Ober, Carole; Nicolae, Dan L

    We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma

  11. Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

    NARCIS (Netherlands)

    C.A. Rietveld (Niels); T. Esko (Tõnu); G. Davies (Gail); T.H. Pers (Tune); P. Turley (Patrick); B. Benyamin (Beben); C.F. Chabris (Christopher F.); V. Emilsson (Valur); A.D. Johnson (Andrew); J.J. Lee (James J.); C. de Leeuw (Christiaan); R.E. Marioni (Riccardo); S.E. Medland (Sarah Elizabeth); M. Miller (Mike); O. Rostapshova (Olga); S.J. van der Lee (Sven); A.A.E. Vinkhuyzen (Anna A.); N. Amin (Najaf); D. Conley (Dalton); J. Derringer; C.M. van Duijn (Cornelia); R.S.N. Fehrmann (Rudolf); L. Franke (Lude); E.L. Glaeser (Edward L.); N.K. Hansell (Narelle); C. Hayward (Caroline); W.G. Iacono (William); C.A. Ibrahim-Verbaas (Carla); V.W.V. Jaddoe (Vincent); J. Karjalainen (Juha); D. Laibson (David); P. Lichtenstein (Paul); D.C. Liewald (David C.); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); G. Mcmahon (George); N.L. Pedersen (Nancy); S. Pinker (Steven); D.J. Porteous (David J.); D. Posthuma (Danielle); F. Rivadeneira Ramirez (Fernando); B.H. Smithk (Blair H.); J.M. Starr (John); H.W. Tiemeier (Henning); N.J. Timpsonm (Nicholas J.); M. Trzaskowskin (Maciej); A.G. Uitterlinden (André); F.C. Verhulst (Frank); M.E. Ward (Mary); M.J. Wright (Margaret); G.D. Smith; I.J. Deary (Ian J.); M. Johannesson (Magnus); R. Plomin (Robert); P.M. Visscher (Peter); D.J. Benjamin (Daniel J.); D. Cesarini (David); Ph.D. Koellinger (Philipp)

    2014-01-01

    textabstractWe identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69

  12. 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...

  13. Genome-wide Association Study Identifies New Loci for Resistance to Leptosphaeria maculans in Canola

    Science.gov (United States)

    Raman, Harsh; Raman, Rosy; Coombes, Neil; Song, Jie; Diffey, Simon; Kilian, Andrzej; Lindbeck, Kurt; Barbulescu, Denise M.; Batley, Jacqueline; Edwards, David; Salisbury, Phil A.; Marcroft, Steve

    2016-01-01

    Key message “We identified both quantitative and quantitative resistance loci to Leptosphaeria maculans, a fungal pathogen, causing blackleg disease in canola. Several genome-wide significant associations were detected at known and new loci for blackleg resistance. We further validated statistically significant associations in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance in canola.” Blackleg, caused by Leptosphaeria maculans, is a significant disease which affects the sustainable production of canola (Brassica napus). This study reports a genome-wide association study based on 18,804 polymorphic SNPs to identify loci associated with qualitative and quantitative resistance to L. maculans. Genomic regions delimited with 694 significant SNP markers, that are associated with resistance evaluated using 12 single spore isolates and pathotypes from four canola stubble were identified. Several significant associations were detected at known disease resistance loci including in the vicinity of recently cloned Rlm2/LepR3 genes, and at new loci on chromosomes A01/C01, A02/C02, A03/C03, A05/C05, A06, A08, and A09. In addition, we validated statistically significant associations on A01, A07, and A10 in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance and mapped within 13.2 kb from Arabidopsis R gene of TIR-NBS class. We showed that resistance loci are located in the vicinity of R genes of Arabidopsis thaliana and Brassica napus on the sequenced genome of B. napus cv. Darmor-bzh. Significantly associated SNP markers provide a valuable tool to enrich germplasm for favorable alleles in order to improve the level of resistance to L. maculans in

  14. A genome-wide association study using international breeding-evaluation data identifies major loci affecting production traits and stature in the Brown Swiss cattle breed

    Directory of Open Access Journals (Sweden)

    Guo Jiazhong

    2012-10-01

    Full Text Available Abstract Background The genome-wide association study (GWAS is a useful approach to identify genes affecting economically important traits in dairy cattle. Here, we report the results from a GWAS based on high-density SNP genotype data and estimated breeding values for nine production, fertility, body conformation, udder health and workability traits in the Brown Swiss cattle population that is part of the international genomic evaluation program. Result GWASs were performed using 50 k SNP chip data and deregressed estimated breeding values (DEBVs for nine traits from between 2061 and 5043 bulls that were part of the international genomic evaluation program coordinated by Interbull Center. The nine traits were milk yield (MY, fat yield (FY, protein yield (PY, lactating cow’s ability to recycle after calving (CRC, angularity (ANG, body depth (BDE, stature (STA, milk somatic cell score (SCS and milk speed (MSP. Analyses were performed using a linear mixed model correcting for population confounding. A total of 74 SNPs were detected to be genome-wide significantly associated with one or several of the nine analyzed traits. The strongest signal was identified on chromosome 25 for milk production traits, stature and body depth. Other signals were on chromosome 11 for angularity, chromosome 24 for somatic cell score, and chromosome 6 for milking speed. Some signals overlapped with earlier reported QTL for similar traits in other cattle populations and were located close to interesting candidate genes worthy of further investigations. Conclusions Our study shows that international genetic evaluation data is a useful resource for identifying genetic factors influencing complex traits in livestock. Several genome wide significant association signals could be identified in the Brown Swiss population, including a major signal on BTA25. Our findings report several associations and plausible candidate genes that deserve further exploration in other

  15. Genome wide association and linkage analyses identified three loci -- 4q25, 17q23.2 and 10q11.21 -- associated with variation in leukocyte telomere length: The Long Life Family Study

    Directory of Open Access Journals (Sweden)

    Joseph H Lee

    2014-01-01

    Full Text Available Leukocyte telomere length is believed to measure cellular aging in humans, and short leukocyte telomere length is associated with increased risks of late onset diseases, including cardiovascular disease, dementia, etc. Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including TERT, TERC, OBFC1, and CTC1. Unlike most studies that have focused on genetic causes of chronic diseases such as heart disease and diabetes in relation to leukocyte telomere length, the present study examined the genome to identify variants that may contribute to variation in leukocyte telomere length among families with exceptional longevity. From the genome wide association analysis in 4,289 LLFS participants, we identified a novel intergenic SNP rs7680468 located near PAPSS1 and DKK2 on 4q25 (p=4.7E-8. From our linkage analysis, we identified two additional loci with HLOD scores exceeding three, including 4.77 for 17q23.2 and 4.36 for 10q11.21. These two loci harbor a number of novel candidate genes with SNPs, and our gene-wise association analysis identified multiple genes, including DCAF7, POLG2, CEP95, and SMURF2 at 17q23.2; and RASGEF1A, HNRNPF, ANF487, CSTF2T, and PRKG1 at 10q11.21. Among these genes, multiple SNPs were associated with leukocyte telomere length, but the strongest association was observed with one contiguous haplotype in CEP95 and SMURF2. We also show that three previously reported genes – TERC, MYNN, and OBFC1 – were significantly associated with leukocyte telomere length at pempirical smaller than 0.05.

  16. Association analysis identifies TLR7 and TLR8 as novel risk genes in asthma and related disorders

    DEFF Research Database (Denmark)

    Møller-Larsen, S; Nyegaard, M; Haagerup, A

    2008-01-01

    of both TLR7 and 8 in all four phenotypes investigated: asthma, rhinitis, atopic dermatitis and increased specific IgE. The most significant association was seen for rs2407992 (TLR8) in asthma (p = 0.00023, sample A and B combined, recessive model). In TLR7, rs179008 showed the strongest association. Both...... rs179008 and rs2407992 are of putative functional significance, potentially affecting TLR7 processing and TLR8 splicing, respectively. Haplotypes comprising the major alleles of these two SNPs were overtransmitted to the affected offspring (eg, p = 0.00012 in asthma, combined sample, additive model...... the TLR7 and TLR8 genes. METHODS: The involvement of TLR7 and TLR8 in the aetiology of asthma and related disorders was investigated by a family based association analysis of two independently ascertained family samples comprising 540 and 424 individuals from 135 and 100 families, respectively. Ten...

  17. Genome-wide Association Study Identifies New Loci for Resistance to Leptosphaeria maculans in Canola

    Directory of Open Access Journals (Sweden)

    Harsh Raman

    2016-10-01

    Full Text Available Blackleg, caused by Leptosphaeria maculans, is a significant disease which affects the sustainable production of canola. This study reports a genome-wide association study based on 18,804 polymorphic SNPs to identify loci associated with qualitative and quantitative resistance to L. maculans. Genomic regions delimited with 503 significant SNP markers, that are associated with resistance evaluated using 12 single spore isolates and pathotypes from four canola stubble were identified. Several significant associations were detected at known disease resistance loci including in the vicinity of recently cloned Rlm2/LepR3 genes, and at new loci on chromosomes A01/C01, A02/C02, A03/C03, A05/C05, A06, A08, and A09. In addition, we validated statistically significant associations on A01, A07 and A10 in four genetic mapping populations, demonstrating that GWAS marker loci are indeed associated with resistance to L. maculans. One of the novel loci identified for the first time, Rlm12, conveys adult plant resistance and mapped within 13.2 kb from Arabidopsis R gene of TIR-NBS class. We showed that resistance loci are located in the vicinity of R genes of A. thaliana and B. napus on the sequenced genome of B. napus cv. Darmor-bzh. Significantly associated SNP markers provide a valuable tool to enrich germplasm for favorable alleles in order to improve the level of resistance to L. maculans in canola.

  18. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    DEFF Research Database (Denmark)

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge...... by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son familial risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT...

  19. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

    Science.gov (United States)

    Reveille, John D; Sims, Anne-Marie; Danoy, Patrick; Evans, David M; Leo, Paul; Pointon, Jennifer J; Jin, Rui; Zhou, Xiaodong; Bradbury, Linda A; Appleton, Louise H; Davis, John C; Diekman, Laura; Doan, Tracey; Dowling, Alison; Duan, Ran; Duncan, Emma L; Farrar, Claire; Hadler, Johanna; Harvey, David; Karaderi, Tugce; Mogg, Rebecca; Pomeroy, Emma; Pryce, Karena; Taylor, Jacqueline; Savage, Laurie; Deloukas, Panos; Kumanduri, Vasudev; Peltonen, Leena; Ring, Sue M; Whittaker, Pamela; Glazov, Evgeny; Thomas, Gethin P; Maksymowych, Walter P; Inman, Robert D; Ward, Michael M; Stone, Millicent A; Weisman, Michael H; Wordsworth, B Paul; Brown, Matthew A

    2011-01-01

    To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility. PMID:20062062

  20. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci.

    Science.gov (United States)

    Reveille, John D; Sims, Anne-Marie; Danoy, Patrick; Evans, David M; Leo, Paul; Pointon, Jennifer J; Jin, Rui; Zhou, Xiaodong; Bradbury, Linda A; Appleton, Louise H; Davis, John C; Diekman, Laura; Doan, Tracey; Dowling, Alison; Duan, Ran; Duncan, Emma L; Farrar, Claire; Hadler, Johanna; Harvey, David; Karaderi, Tugce; Mogg, Rebecca; Pomeroy, Emma; Pryce, Karena; Taylor, Jacqueline; Savage, Laurie; Deloukas, Panos; Kumanduri, Vasudev; Peltonen, Leena; Ring, Sue M; Whittaker, Pamela; Glazov, Evgeny; Thomas, Gethin P; Maksymowych, Walter P; Inman, Robert D; Ward, Michael M; Stone, Millicent A; Weisman, Michael H; Wordsworth, B Paul; Brown, Matthew A

    2010-02-01

    To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.

  1. Whole-Exome Sequencing to Identify Novel Biological Pathways Associated With Infertility After Pelvic Inflammatory Disease.

    Science.gov (United States)

    Taylor, Brandie D; Zheng, Xiaojing; Darville, Toni; Zhong, Wujuan; Konganti, Kranti; Abiodun-Ojo, Olayinka; Ness, Roberta B; O'Connell, Catherine M; Haggerty, Catherine L

    2017-01-01

    Ideal management of sexually transmitted infections (STI) may require risk markers for pathology or vaccine development. Previously, we identified common genetic variants associated with chlamydial pelvic inflammatory disease (PID) and reduced fecundity. As this explains only a proportion of the long-term morbidity risk, we used whole-exome sequencing to identify biological pathways that may be associated with STI-related infertility. We obtained stored DNA from 43 non-Hispanic black women with PID from the PID Evaluation and Clinical Health Study. Infertility was assessed at a mean of 84 months. Principal component analysis revealed no population stratification. Potential covariates did not significantly differ between groups. Sequencing kernel association test was used to examine associations between aggregates of variants on a single gene and infertility. The results from the sequencing kernel association test were used to choose "focus genes" (P < 0.01; n = 150) for subsequent Ingenuity Pathway Analysis to identify "gene sets" that are enriched in biologically relevant pathways. Pathway analysis revealed that focus genes were enriched in canonical pathways including, IL-1 signaling, P2Y purinergic receptor signaling, and bone morphogenic protein signaling. Focus genes were enriched in pathways that impact innate and adaptive immunity, protein kinase A activity, cellular growth, and DNA repair. These may alter host resistance or immunopathology after infection. Targeted sequencing of biological pathways identified in this study may provide insight into STI-related infertility.

  2. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    DEFF Research Database (Denmark)

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur

    2010-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combi......By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals...

  3. A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.

    Science.gov (United States)

    Kapoor, Manav; Wang, Jen-Chyong; Wetherill, Leah; Le, Nhung; Bertelsen, Sarah; Hinrichs, Anthony L; Budde, John; Agrawal, Arpana; Bucholz, Kathleen; Dick, Danielle; Harari, Oscar; Hesselbrock, Victor; Kramer, John; Nurnberger, John I; Rice, John; Saccone, Nancy; Schuckit, Marc; Tischfield, Jay; Porjesz, Bernice; Edenberg, Howard J; Bierut, Laura; Foroud, Tatiana; Goate, Alison

    2013-10-01

    Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10(-6)) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10(-7)), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10(-7)) and PLCL1 genes (p = 4.1 × 10(-6)) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10(-4)) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10(-3), 3 × 10(-6)), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.

  4. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

    OpenAIRE

    Reveille, John D; Sims, Anne-Marie; Danoy, Patrick; Evans, David M; Leo, Paul; Pointon, Jennifer J; Jin, Rui; Zhou, Xiaodong; Bradbury, Linda A; Appleton, Louise H; Davis, John C; Diekman, Laura; Doan, Tracey; Dowling, Alison; Duan, Ran

    2010-01-01

    To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10−800), we found associa...

  5. Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus.

    Science.gov (United States)

    Aterido, Adrià; Julià, Antonio; Carreira, Patricia; Blanco, Ricardo; López-Longo, José Javier; Venegas, José Javier Pérez; Olivé, Àlex; Andreu, José Luís; Aguirre-Zamorano, Maria Ángeles; Vela, Paloma; Nolla, Joan M; Marenco-de la Fuente, José Luís; Zea, Antonio; Pego, José María; Freire, Mercedes; Díez, Elvira; López-Lasanta, María; López-Corbeto, Mireia; Palau, Núria; Tortosa, Raül; Gelpí, Josep Lluís; Absher, Devin; Myers, Richard M; Fernández-Nebro, Antonio; Marsal, Sara

    2017-06-15

    Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR ) oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis

  6. A Genome-Wide Association Study to Identify Diagnostic Markers for Human Pathogenic Campylobacter jejuni Strains

    Directory of Open Access Journals (Sweden)

    Cody J. Buchanan

    2017-06-01

    Full Text Available Campylobacter jejuni is a leading human enteric pathogen worldwide and despite an improved understanding of its biology, ecology, and epidemiology, limited tools exist for identifying strains that are likely to cause disease. In the current study, we used subtyping data in a database representing over 24,000 isolates collected through various surveillance projects in Canada to identify 166 representative genomes from prevalent C. jejuni subtypes for whole genome sequencing. The sequence data was used in a genome-wide association study (GWAS aimed at identifying accessory gene markers associated with clinically related C. jejuni subtypes. Prospective markers (n = 28 were then validated against a large number (n = 3,902 of clinically associated and non-clinically associated genomes from a variety of sources. A total of 25 genes, including six sets of genetically linked genes, were identified as robust putative diagnostic markers for clinically related C. jejuni subtypes. Although some of the genes identified in this study have been previously shown to play a role in important processes such as iron acquisition and vitamin B5 biosynthesis, others have unknown function or are unique to the current study and warrant further investigation. As few as four of these markers could be used in combination to detect up to 90% of clinically associated isolates in the validation dataset, and such markers could form the basis for a screening assay to rapidly identify strains that pose an increased risk to public health. The results of the current study are consistent with the notion that specific groups of C. jejuni strains of interest are defined by the presence of specific accessory genes.

  7. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

    NARCIS (Netherlands)

    Couch, Fergus J.; Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, Francois; Vincent, Daniel; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; van Rensburg, Elizabeth J.; Hamann, Ute; Ramus, Susan J.; Toland, Amanda Ewart; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmana, Judith; Barkardottir, Rosa B.; Arun, Banu K.; Rennert, Gad; Teo, Soo-Hwang; Ganz, Patricia A.; Campbell, Ian; van der Hout, Annemarie; van Deurzen, Carolien H. M.; Seynaeve, Caroline; Garcia, Encarna B. Gomez; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Gille, Johannes J. P.; Ausems, Margreet G. E. M.; Blok, Marinus J.; Ligtenberg, Marjolijn J. L.; Rookus, Matti A.; Devilee, Peter; Verhoef, Senno; van Os, Theo A. M.; Wijnen, Juul T.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Izatt, Louise; Eeles, Rosalind A.; Adlard, Julian; Eccles, Diana M.; Cook, Jackie; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley; Morrison, Patrick J.; Side, Lucy E.; Donaldson, Alan; Houghton, Catherine; Rogers, Mark T.; Dorkins, Huw; Eason, Jacqueline; Gregory, Helen; McCann, Emma; Murray, Alex; Calender, Alain; Hardouin, Agnes; Berthet, Pascaline; Delnatte, Capucine; Nogues, Catherine; Lasset, Christine; Houdayer, Claude; Leroux, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Sobol, Hagay; Coupier, Isabelle; Venat-Bouvet, Laurence; Castera, Laurent; Gauthier-Villars, Marion; Leone, Melanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Zlowocka-Perlowska, Elzbieta; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska, Katarzyna; Huzarski, Tomasz; Spurdle, Amanda B.; Viel, Alessandra; Peissel, Bernard; Bonanni, Bernardo; Melloni, Giulia; Ottini, Laura; Papi, Laura; Varesco, Liliana; Tibiletti, Maria Grazia; Peterlongo, Paolo; Volorio, Sara; Manoukian, Siranoush; Pensotti, Valeria; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Gadzicki, Dorothea; Gehrig, Andrea; Kast, Karin; Rhiem, Kerstin; Meindl, Alfons; Niederacher, Dieter; Ditsch, Nina; Plendl, Hansjoerg; Preisler-Adams, Sabine; Engert, Stefanie; Sutter, Christian; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Weber, Bernhard H. F.; Arver, Brita; Stenmark-Askmalm, Marie; Loman, Niklas; Rosenquist, Richard; Einbeigi, Zakaria; Nathanson, Katherine L.; Rebbeck, Timothy R.; Blank, Stephanie V.; Cohn, David E.; Rodriguez, Gustavo C.; Small, Laurie; Friedlander, Michael; Bae-Jump, Victoria L.; Fink-Retter, Anneliese; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Tea, Muy-Kheng; Lindor, Noralane M.; Kaufman, Bella; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Vijai, Joseph; Sarrel, Kara; Robson, Mark; Kauff, Noah; Mulligan, Anna Marie; Glendon, Gord; Ozcelik, Hilmi; Ejlertsen, Bent; Nielsen, Finn C.; Jonson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teule, Alex; Lazaro, Conxi; Brunet, Joan; Angel Pujana, Miquel; Mai, Phuong L.; Loud, Jennifer T.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Narod, Steven A.; Herzog, Josef; Sand, Sharon R.; Tognazzo, Silvia; Agata, Simona; Vaszko, Tibor; Weaver, Joellen; Stavropoulou, Alexandra V.; Buys, Saundra S.; Romero, Atocha; de la Hoya, Miguel; Aittomaki, Kristiina; Muranen, Taru A.; Duran, Mercedes; Chung, Wendy K.; Lasa, Adriana; Dorfling, Cecilia M.; Miron, Alexander; Benitez, Javier; Senter, Leigha; Huo, Dezheng; Chan, Salina B.; Sokolenko, Anna P.; Chiquette, Jocelyne; Tihomirova, Laima; Friebel, Tara M.; Agnarsson, Bjarni A.; Lu, Karen H.; Lejbkowicz, Flavio; James, Paul A.; Hall, Per; Dunning, Alison M.; Tessier, Daniel; Cunningham, Julie; Slager, Susan L.; Wang, Chen; Hart, Steven; Stevens, Kristen; Simard, Jacques; Pastinen, Tomi; Pankratz, Vernon S.; Offit, Kenneth; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

    2013-01-01

    BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a

  8. Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk

    NARCIS (Netherlands)

    Couch, Fergus J.; Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, François; Vincent, Daniel; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; van Rensburg, Elizabeth J.; Hamann, Ute; Ramus, Susan J.; Toland, Amanda Ewart; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmaña, Judith; Barkardottir, Rosa B.; Arun, Banu K.; Rennert, Gad; teo, Soo-Hwang; Ganz, Patricia A.; Campbell, Ian; van der Hout, Annemarie H.; van Deurzen, Carolien H. M.; Seynaeve, Caroline; Gómez Garcia, Encarna B.; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Gille, Johannes J. P.; Ausems, Margreet G. E. M.; Blok, Marinus J.; Ligtenberg, Marjolijn J. L.; Rookus, Matti A.; Devilee, Peter; Verhoef, Senno; van Os, Theo A. M.; Wijnen, Juul T.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Izatt, Louise; Eeles, Rosalind A.; Adlard, Julian; Eccles, Diana M.; Cook, Jackie; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley; Morrison, Patrick J.; Side, Lucy E.; Donaldson, Alan; Houghton, Catherine; Rogers, Mark T.; Dorkins, Huw; Eason, Jacqueline; Gregory, Helen; McCann, Emma; Murray, Alex; Calender, Alain; Hardouin, Agnès; Berthet, Pascaline; Delnatte, Capucine; Nogues, Catherine; Lasset, Christine; Houdayer, Claude; Leroux, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Sobol, Hagay; Coupier, Isabelle; Venat-Bouvet, Laurence; Castera, Laurent; Gauthier-Villars, Marion; Léoné, Mélanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Złowocka-Perłowska, Elżbieta; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska, Katarzyna; Huzarski, Tomasz; Spurdle, Amanda B.; Viel, Alessandra; Peissel, Bernard; Bonanni, Bernardo; Melloni, Giulia; Ottini, Laura; Papi, Laura; Varesco, Liliana; Tibiletti, Maria Grazia; Peterlongo, Paolo; Volorio, Sara; Manoukian, Siranoush; Pensotti, Valeria; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Gadzicki, Dorothea; Gehrig, Andrea; Kast, Karin; Rhiem, Kerstin; Meindl, Alfons; Niederacher, Dieter; Ditsch, Nina; Plendl, Hansjoerg; Preisler-Adams, Sabine; Engert, Stefanie; Sutter, Christian; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Weber, Bernhard H. F.; Arver, Brita; Stenmark-Askmalm, Marie; Loman, Niklas; Rosenquist, Richard; Einbeigi, Zakaria; Nathanson, Katherine L.; Rebbeck, Timothy R.; Blank, Stephanie V.; Cohn, David E.; Rodriguez, Gustavo C.; Small, Laurie; Friedlander, Michael; Bae-Jump, Victoria L.; Fink-Retter, Anneliese; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; tea, Muy-Kheng; Lindor, Noralane M.; Kaufman, Bella; Shimon Paluch, Shani; Laitman, Yael; Skytte, Anne-Bine; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Vijai, Joseph; Sarrel, Kara; Robson, Mark; Kauff, Noah; Mulligan, Anna Marie; Glendon, Gord; Ozcelik, Hilmi; Ejlertsen, Bent; Nielsen, Finn C.; Jønson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teulé, Alex; Lazaro, Conxi; Brunet, Joan; Pujana, Miquel Angel; Mai, Phuong L.; Loud, Jennifer T.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Narod, Steven A.; Herzog, Josef; Sand, Sharon R.; Tognazzo, Silvia; Agata, Simona; Vaszko, Tibor; Weaver, Joellen; Stavropoulou, Alexandra V.; Buys, Saundra S.; Romero, Atocha; de la Hoya, Miguel; Aittomäki, Kristiina; Muranen, Taru A.; Duran, Mercedes; Chung, Wendy K.; Lasa, Adriana; Dorfling, Cecilia M.; Miron, Alexander; Benitez, Javier; Senter, Leigha; Huo, Dezheng; Chan, Salina B.; Sokolenko, Anna P.; Chiquette, Jocelyne; Tihomirova, Laima; Friebel, Tara M.; Agnarsson, Bjarni A.; Lu, Karen H.; Lejbkowicz, Flavio; James, Paul A.; Hall, Per; Dunning, Alison M.; Tessier, Daniel; Cunningham, Julie; Slager, Susan L.; Wang, Chen; Hart, Steven; Stevens, Kristen; Simard, Jacques; Pastinen, Tomi; Pankratz, Vernon S.; Offit, Kenneth; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

    2013-01-01

    BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a

  9. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

    NARCIS (Netherlands)

    F.J. Couch (Fergus); X. Wang (Xing); L. McGuffog (Lesley); A. Lee (Andrew); C. Olswold (Curtis); K.B. Kuchenbaecker (Karoline); P. Soucy (Penny); Z. Fredericksen (Zachary); D. Barrowdale (Daniel); J. Dennis (Joe); M.M. Gaudet (Mia); E. Dicks (Ed); M. Kosel (Matthew); S. Healey (Sue); O. Sinilnikova (Olga); F. Bacot (Francois); D. Vincent (Daniel); F.B.L. Hogervorst (Frans); S. Peock (Susan); D. Stoppa-Lyonnet (Dominique); A. Jakubowska (Anna); P. Radice (Paolo); R.K. Schmutzler (Rita); S.M. Domchek (Susan); M. Piedmonte (Marion); C.F. Singer (Christian); E. Friedman (Eitan); M. Thomassen (Mads); T.V.O. Hansen (Thomas); S.L. Neuhausen (Susan); C. Szabo (Csilla); I. Blanco (Ignacio); M.H. Greene (Mark); B.Y. Karlan (Beth); J. Garber; C. Phelan (Catherine); J.N. Weitzel (Jeffrey); M. Montagna (Marco); E. Olah; I.L. Andrulis (Irene); A.K. Godwin (Andrew); D. Yannoukakos (Drakoulis); D. Goldgar (David); T. Caldes (Trinidad); H. Nevanlinna (Heli); A. Osorio (Ana); M.-B. Terry (Mary-Beth); M.B. Daly (Mary); E.J. van Rensburg (Elizabeth); U. Hamann (Ute); S.J. Ramus (Susan); A. Ewart-Toland (Amanda); M.A. Caligo (Maria); O.I. Olopade (Olofunmilayo); N. Tung (Nadine); K. Claes (Kathleen); M.S. Beattie (Mary); M.C. Southey (Melissa); E.N. Imyanitov (Evgeny); M. Tischkowitz (Marc); R. Janavicius (Ramunas); E.M. John (Esther); A. Kwong (Ava); O. Diez (Orland); J. Balmana (Judith); R.B. Barkardottir (Rosa); B.K. Arun (Banu); G. Rennert (Gad); S.-H. Teo (Soo-Hwang); P.A. Ganz (Patricia); I. Campbell (Ian); A.H. van der Hout (Annemarie); C.H.M. van Deurzen (Carolien); C.M. Seynaeve (Caroline); E.B. Gómez García (Encarna); F.E. van Leeuwen (F.); H. Meijers-Heijboer (Hanne); J.J. Gille (Johan); M.G.E.M. Ausems (Margreet); M.J. Blok (Marinus); M.J. Ligtenberg (Marjolijn); M.A. Rookus (Matti); P. Devilee (Peter); S. Verhoef; T.A.M. van Os (Theo); J.T. Wijnen (Juul); D. Frost (Debra); S. Ellis (Steve); E. Fineberg (Elena); R. Platte (Radka); D.G. Evans (Gareth); L. Izatt (Louise); R. Eeles (Rosalind); J.W. Adlard (Julian); D. Eccles (Diana); J. Cook (Jackie); C. Brewer (C.); F. Douglas (Fiona); S.V. Hodgson (Shirley); P.J. Morrison (Patrick); L. Side (Lucy); A. Donaldson (Alan); C. Houghton (Catherine); M.T. Rogers (Mark); H. Dorkins (Huw); J. Eason (Jacqueline); H. Gregory (Helen); E. McCann (Emma); A. Murray (Alexandra); A. Calender (Alain); A. Hardouin (Agnès); P. Berthet (Pascaline); C.D. Delnatte (Capucine); C. Nogues (Catherine); C. Lasset (Christine); C. Houdayer (Claude); D. Leroux (Dominique); E. Rouleau (Etienne); F. Prieur (Fabienne); F. Damiola (Francesca); H. Sobol (Hagay); I. Coupier (Isabelle); L. Vénat-Bouvet (Laurence); L. Castera (Laurent); M. Gauthier-Villars (Marion); M. Léone (Mélanie); P. Pujol (Pascal); S. Mazoyer (Sylvie); Y.-J. Bignon (Yves-Jean); E. Złowocka-Perłowska (Elzbieta); J. Gronwald (Jacek); J. Lubinski (Jan); K. Durda (Katarzyna); K. Jaworska (Katarzyna); T. Huzarski (Tomasz); A.B. Spurdle (Amanda); A. Viel (Alessandra); B. Peissel (Bernard); B. Bonnani (Bernardo); G. Melloni (Giulia); L. Ottini (Laura); L. Papi (Laura); L. Varesco (Liliana); M.G. Tibiletti (Maria Grazia); P. Peterlongo (Paolo); S. Volorio (Sara); S. Manoukian (Siranoush); V. Pensotti (Valeria); N. Arnold (Norbert); C.W. Engel (Christoph); H. Deissler (Helmut); D. Gadzicki (Dorothea); P.A. Gehrig (Paola A.); K. Kast (Karin); K. Rhiem (Kerstin); A. Meindl (Alfons); D. Niederacher (Dieter); N. Ditsch (Nina); H. Plendl (Hansjoerg); S. Preisler-Adams (Sabine); S. Engert (Stefanie); C. Sutter (Christian); R. Varon-Mateeva (Raymonda); B. Wapenschmidt (Barbara); B.H.F. Weber (Bernhard); B. Arver (Brita Wasteson); M. Stenmark-Askmalm (M.); N. Loman (Niklas); R. Rosenquist (R.); Z. Einbeigi (Zakaria); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); S.V. Blank (Stephanie); D.E. Cohn (David); G.C. Rodriguez (Gustavo); L. Small (Laurie); M. Friedlander (Michael); V.L. Bae-Jump (Victoria L.); A. Fink-Retter (Anneliese); C. Rappaport (Christine); D. Gschwantler-Kaulich (Daphne); G. Pfeiler (Georg); M.-K. Tea; N.M. Lindor (Noralane); B. Kaufman (Bella); S. Shimon Paluch (Shani); Y. Laitman (Yael); A.-B. Skytte (Anne-Bine); A-M. Gerdes (Anne-Marie); I.S. Pedersen (Inge Sokilde); S.T. Moeller (Sanne Traasdahl); T.A. Kruse (Torben); U.B. Jensen; J. Vijai (Joseph); K. Sarrel (Kara); M. Robson (Mark); N. Kauff (Noah); A.M. Mulligan (Anna Marie); G. Glendon (Gord); H. Ozcelik (Hilmi); B. Ejlertsen (Bent); F.C. Nielsen (Finn); L. Jønson (Lars); M.K. Andersen (Mette); Y.C. Ding (Yuan); L. Steele (Linda); L. Foretova (Lenka); A. Teulé (A.); C. Lazaro (Conxi); J. Brunet (Joan); M.A. Pujana (Miguel); P.L. Mai (Phuong); J.T. Loud (Jennifer); C.S. Walsh (Christine); K.J. Lester (Kathryn); S. Orsulic (Sandra); S. Narod (Steven); J. Herzog (Josef); S.R. Sand (Sharon); S. Tognazzo (Silvia); S. Agata (Simona); T. Vaszko (Tibor); J. Weaver (JoEllen); A. Stavropoulou (Alexandra); S.S. Buys (Saundra); A. Romero (Alfonso); M. de La Hoya (Miguel); K. Aittomäki (Kristiina); T.A. Muranen (Taru); M. Durán (Mercedes); W.K. Chung (Wendy); A. Lasa (Adriana); C.M. Dorfling (Cecelia); A. Miron (Alexander); J. Benítez (Javier); L. Senter (Leigha); D. Huo (Dezheng); S. Chan (Salina); A. Sokolenko (Anna); J. Chiquette (Jocelyne); L. Tihomirova (Laima); M.O.W. Friebel (Mark ); B.A. Agnarsson (Bjarni); K.H. Lu (Karen); F. Lejbkowicz (Flavio); P.A. James (Paul ); A.S. Hall (Alistair); A.M. Dunning (Alison); Y. Tessier (Yann); J. Cunningham (Jane); S. Slager (Susan); C. Wang (Chen); S. Hart (Stewart); K. Stevens (Kristen); J. Simard (Jacques); T. Pastinen (Tomi); V.S. Pankratz (Shane); K. Offit (Kenneth); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis); H. Thorne (Heather); E. Niedermayr (Eveline); Å. Borg (Åke); H. Olsson; H. Jernström (H.); K. Henriksson (Karin); K. Harbst (Katja); M. Soller (Maria); U. Kristoffersson (Ulf); A. Öfverholm (Anna); M. Nordling (Margareta); P. Karlsson (Per); A. von Wachenfeldt (Anna); A. Liljegren (Annelie); A. Lindblom (Annika); G.B. Bustinza; J. Rantala (Johanna); B. Melin (Beatrice); C.E. Ardnor (Christina Edwinsdotter); M. Emanuelsson (Monica); H. Ehrencrona (Hans); M.H. Pigg (Maritta ); S. Liedgren (Sigrun); M.A. Rookus (M.); S. Verhoef (S.); F.E. van Leeuwen (F.); M.K. Schmidt (Marjanka); J.L. de Lange (J.); J.M. Collée (Margriet); A.M.W. van den Ouweland (Ans); M.J. Hooning (Maartje); C.J. van Asperen (Christi); J.T. Wijnen (Juul); R.A.E.M. Tollenaar (Rob); P. Devilee (Peter); T.C.T.E.F. van Cronenburg; C.M. Kets; A.R. Mensenkamp (Arjen); R.B. van der Luijt (Rob); C.M. Aalfs (Cora); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gomez Garcia (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits (Marjan); G.H. de Bock (Geertruida); S.D. Ellis (Steve); E. Fineberg (Elena); Z. Miedzybrodzka (Zosia); L. Jeffers (Lisa); T.J. Cole (Trevor); K.-R. Ong (Kai-Ren); J. Hoffman (Jonathan); M. James (Margaret); J. Paterson (Joan); A. Taylor (Amy); A. Murray (Anna); M.J. Kennedy (John); D.E. Barton (David); M.E. Porteous (Mary); S. Drummond (Sarah); C. Brewer (Carole); E. Kivuva (Emma); A. Searle (Anne); S. Goodman (Selina); R. Davidson (Rosemarie); V. Murday (Victoria); N. Bradshaw (Nicola); L. Snadden (Lesley); M. Longmuir (Mark); C. Watt (Catherine); S. Gibson (Sarah); E. Haque (Eshika); E. Tobias (Ed); A. Duncan (Alexis); L. Izatt (Louise); C. Jacobs (Chris); C. Langman (Caroline); A.F. Brady (Angela); S.A. Melville (Scott); K. Randhawa (Kashmir); J. Barwell (Julian); G. Serra-Feliu (Gemma); I.O. Ellis (Ian); F. Lalloo (Fiona); J. Taylor (James); A. Male (Alison); C. Berlin (Cheryl); R. Collier (Rebecca); F. Douglas (Fiona); O. Claber (Oonagh); I. Jobson (Irene); L.J. Walker (Lisa); D. McLeod (Diane); D. Halliday (Dorothy); S. Durell (Sarah); B. Stayner (Barbara); S. Shanley (Susan); N. Rahman (Nazneen); R. Houlston (Richard); A. Stormorken (Astrid); E.K. Bancroft (Elizabeth); E. Page (Elizabeth); A. Ardern-Jones (Audrey); K. Kohut (Kelly); J. Wiggins (Jennifer); E. Castro (Elena); S.R. Killick; S. Martin (Sue); D. Rea (Dan); A. Kulkarni (Anjana); O. Quarrell (Oliver); C. Bardsley (Cathryn); S. Goff (Sheila); G. Brice (Glen); L. Winchester (Lizzie); C. Eddy (Charlotte); V. Tripathi (Vishakha); V. Attard (Virginia); A. Lehmann (Anna); A. Lucassen (Anneke); G. Crawford (Gabe); D. McBride (Donna); S. Smalley (Sarah); S. Mazoyer (Sylvie); F. Damiola (Francesca); L. Barjhoux (Laure); C. Verny-Pierre (Carole); S. Giraud (Sophie); D. Stoppa-Lyonnet (Dominique); B. Buecher (Bruno); V. Moncoutier (Virginie); M. Belotti (Muriel); C. Tirapo (Carole); A. de Pauw (Antoine); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); V. Bonadona (Valérie); S. Handallou (Sandrine); A. hardouin (Agnès); H. Sobol (Hagay); V. Bourdon (Violaine); T. Noguchi (Tetsuro); A. Remenieras (Audrey); F. Eisinger (François); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); P. Vennin (Philippe); C. Adenis (Claude); R. Lidereau (Rosette); L. Demange (Liliane); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); H. Dreyfus (Hélène); C. Rebischung (Christine); M. Peysselon (Magalie); F. Coron (Fanny); L. Faivre (Laurence); M. Lebrun (Marine); C. Kientz (Caroline); S.F. Ferrer; M. Frenay (Marc); I. Mortemousque (Isabelle); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; J. Sokolowska (Johanna); M. Bronner (Myriam); H. Lynch (Henry); C.L. Snyder (Carrie); M. Angelakos (Maggie); J. Maskiell (Judi); G.S. Dite (Gillian)

    2013-01-01

    textabstractBRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer),

  10. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic...

  11. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk.

    NARCIS (Netherlands)

    Couch, F.J.; Wang, X.; McGuffog, L.; Lee, A.; Olswold, C.; Kuchenbaecker, K.B.; Soucy, P.; Fredericksen, Z.; Barrowdale, D.; Dennis, J.; Gaudet, M.M.; Dicks, E.; Kosel, M.; Healey, S.; Sinilnikova, O.M.; Bacot, F.; Vincent, D.; Hogervorst, F.B.; Peock, S.; Stoppa-Lyonnet, D.; Jakubowska, A.; Radice, P.; Schmutzler, R.K.; Domchek, S.M.; Piedmonte, M.; Singer, C.F.; Friedman, E.; Thomassen, M.; Hansen, T.V.; Neuhausen, S.L.; Szabo, C.I.; Blanco, I.; Greene, M.H.; Karlan, B.Y.; Garber, J.; Phelan, C.M.; Weitzel, J.N.; Montagna, M.; Olah, E.; Andrulis, I.L.; Godwin, A.K.; Yannoukakos, D.; Goldgar, D.E.; Caldes, T.; Nevanlinna, H.; Osorio, A.; Terry, M.B.; Daly, M.B.; Rensburg, E.J. van; Hamann, U.; Ramus, S.J.; Ewart Toland, A.; Caligo, M.A.; Olopade, O.I.; Tung, N.; Claes, K.; Beattie, M.S.; Southey, M.C.; Imyanitov, E.N.; Tischkowitz, M.; Janavicius, R.; John, E.M.; Kwong, A.; Diez, O.; Balmana, J.; Barkardottir, R.B.; Arun, B.K.; Rennert, G.; Teo, S.H.; Ganz, P.A.; Campbell, I.; Hout, A.H. van der; Deurzen, C.H. van; Seynaeve, C.; Gomez Garcia, E.B.; Leeuwen, F.E. van; Meijers-Heijboer, H.E.; Gille, J.J.P.; Ausems, M.G.; Blok, M.J.; Ligtenberg, M.J.L.; Rookus, M.A.; Devilee, P.; Verhoef, S.; Os, T.A. van; Wijnen, J.T.; Frost, D.; Ellis, S.; Fineberg, E.; Platte, R.; Evans, D.G.; Izatt, L.; Eeles, R.A.; Adlard, J.; Eccles, D.M.; Cook, J.; Brewer, C.; Douglas, F.; Hodgson, S.; Morrison, P.J.; Side, L.E.; Donaldson, A.; Houghton, C.; Rogers, M.T.; Dorkins, H.; Eason, J.; Gregory, H.; McCann, E.; Murray, A.; Calender, A.; Hardouin, A.; Berthet, P.; Delnatte, C.; Nogues, C.; Lasset, C.; Houdayer, C.; Leroux, D.; Rouleau, E.; Prieur, F.; Damiola, F.; Sobol, H.; Coupier, I.; Venat-Bouvet, L.; Castera, L.; Gauthier-Villars, M.; Leone, M.; Pujol, P.; Mazoyer, S.; Bignon, Y.J.; Zlowocka-Perlowska, E.; Gronwald, J.; Lubinski, J.; Durda, K.; Jaworska, K.; Huzarski, T.; Spurdle, A.B.; Viel, A.; Peissel, B.; Bonanni, B.; Melloni, G.; Ottini, L.; Papi, L.; Varesco, L.; Tibiletti, M.G.; Peterlongo, P.; Volorio, S.; Manoukian, S.; Pensotti, V.; Arnold, N.; Engel, C.; Deissler, H.; Gadzicki, D.; Gehrig, A.; Kast, K.; Rhiem, K.; Meindl, A.; Niederacher, D.; Ditsch, N.; Plendl, H.; Preisler-Adams, S.; Engert, S.; Sutter, C.; Varon-Mateeva, R.; Wappenschmidt, B.; Weber, B.H.; Arver, B.; Stenmark-Askmalm, M.; Loman, N.; Rosenquist, R.; Einbeigi, Z.; Nathanson, K.L.; Rebbeck, T.R.; Blank, S.V.; Cohn, D.E.; Rodriguez, G.C.; Small, L.; Friedlander, M.; Bae-Jump, V.L.; Fink-Retter, A.; Rappaport, C.; Gschwantler-Kaulich, D.; Pfeiler, G.; Tea, M.K.; Lindor, N.M.; Kaufman, B.; Shimon Paluch, S.; Laitman, Y.; Skytte, A.B.; Gerdes, A.M.; Pedersen, I.S.; Moeller, S.T.; Kruse, T.A.; Jensen, U.B.; Vijai, J.; Sarrel, K.; Robson, M.; Kauff, N.; Mulligan, A.M.; Glendon, G.; Ozcelik, H.; Ejlertsen, B.; Nielsen, F.C.; Jonson, L.; Andersen, M.K.; Ding, Y.C.; Steele, L.; Foretova, L.; Teule, A.; Lazaro, C.; Brunet, J.; Pujana, M.A.; Mai, P.L.; Loud, J.T.; Walsh, C.; Lester, J.; Orsulic, S.; Narod, S.A.; Herzog, J.; Sand, S.R.; Tognazzo, S.; Agata, S.; Vaszko, T.; Weaver, J.; Stavropoulou, A.V.; Buys, S.S.; Romero, A.; Hoya, M. de la; Aittomaki, K.; Muranen, T.A.; Duran, M.; Chung, W.K.; Lasa, A.; Dorfling, C.M.; Miron, A.; Benitez, J.; Senter, L.; Huo, D.; Chan, S.B.; Sokolenko, A.P.; Chiquette, J.; Tihomirova, L.; Friebel, T.M.; Agnarsson, B.A.; Lu, K.H.; Lejbkowicz, F.; James, P.A.; Hall, P.; Dunning, A.M.; Tessier, D.; Cunningham, J.; Slager, S.L.; Wang, C.; Hart, S.; Stevens, K.; Simard, J.; Pastinen, T.; Pankratz, V.S.; Offit, K.; Easton, D.F.; Chenevix-Trench, G.; Antoniou, A.C.; et al.,

    2013-01-01

    BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a

  12. A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions

    Science.gov (United States)

    Oikkonen, J.; Huang, Y.; Onkamo, P.; Ukkola-Vuoti, L.; Raijas, P.; Karma, K.; Vieland, V. J.; Järvelä, I.

    2014-01-01

    Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested. We performed a genome-wide scan in 76 pedigrees (767 individuals) characterized for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception. Using the Bayesian linkage and association approach implemented in program package KELVIN, especially designed for complex pedigrees, several SNPs near genes affecting the functions of the auditory pathway and neurocognitive processes were identified. The strongest association was found at 3q21.3 (rs9854612) with combined SP, ST and KMT test scores (COMB). This region is located a few dozen kilobases upstream of the GATA binding protein 2 (GATA2) gene. GATA2 regulates the development of cochlear hair cells and the inferior colliculus (IC), which are important in tonotopic mapping. The highest probability of linkage was obtained for phenotype SP at 4p14, located next to the region harboring the protocadherin 7 gene, PCDH7. Two SNPs rs13146789 and rs13109270 of PCDH7 showed strong association. PCDH7 has been suggested to play a role in cochlear and amygdaloid complexes. Functional class analysis showed that inner ear and schizophrenia related genes were enriched inside the linked regions. This study is the first to show the importance of auditory pathway genes in musical aptitude. PMID:24614497

  13. A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions.

    Science.gov (United States)

    Oikkonen, J; Huang, Y; Onkamo, P; Ukkola-Vuoti, L; Raijas, P; Karma, K; Vieland, V J; Järvelä, I

    2015-02-01

    Humans have developed the perception, production and processing of sounds into the art of music. A genetic contribution to these skills of musical aptitude has long been suggested. We performed a genome-wide scan in 76 pedigrees (767 individuals) characterized for the ability to discriminate pitch (SP), duration (ST) and sound patterns (KMT), which are primary capacities for music perception. Using the Bayesian linkage and association approach implemented in program package KELVIN, especially designed for complex pedigrees, several single nucleotide polymorphisms (SNPs) near genes affecting the functions of the auditory pathway and neurocognitive processes were identified. The strongest association was found at 3q21.3 (rs9854612) with combined SP, ST and KMT test scores (COMB). This region is located a few dozen kilobases upstream of the GATA binding protein 2 (GATA2) gene. GATA2 regulates the development of cochlear hair cells and the inferior colliculus (IC), which are important in tonotopic mapping. The highest probability of linkage was obtained for phenotype SP at 4p14, located next to the region harboring the protocadherin 7 gene, PCDH7. Two SNPs rs13146789 and rs13109270 of PCDH7 showed strong association. PCDH7 has been suggested to play a role in cochlear and amygdaloid complexes. Functional class analysis showed that inner ear and schizophrenia-related genes were enriched inside the linked regions. This study is the first to show the importance of auditory pathway genes in musical aptitude.

  14. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

    DEFF Research Database (Denmark)

    Demenais, Florence; Margaritte-Jeannin, Patricia; Barnes, Kathleen C

    2018-01-01

    We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known...... asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks...... at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms....

  15. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  16. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

    NARCIS (Netherlands)

    Chami, N. (Nathalie); M.-H. Chen (Ming-Huei); Slater, A.J. (Andrew J.); Eicher, J.D. (John D.); E. Evangelou (Evangelos); Tajuddin, S.M. (Salman M.); Love-Gregory, L. (Latisha); T. Kacprowski (Tim); U.M. Schick (Ursula); Nomura, A. (Akihiro); Giri, A. (Ayush); Lessard, S. (Samuel); J. Brody (Jennifer); C. Schurmann (Claudia); V.S. Pankratz (Shane); L.R. Yanek (Lisa); A. Manichaikul (Ani); R. Pazoki (Raha); E. Mihailov (Evelin); W.D. Hill (W. David); Raffield, L.M. (Laura M.); A.D. Burt (Alastair); T.M. Bartz (Traci M.); D.M. Becker (Diane); L.C. Becker (Lewis); E.A. Boerwinkle (Eric); J. Bork-Jensen (Jette); E.P. Bottinger (Erwin); M.L. O'Donoghue (Michelle L.); D.R. Crosslin (David); de Denus, S. (Simon); Dubé, M.-P. (Marie-Pierre); P. Elliott (Paul); G. Engström; M. Evans (Michele); J. Floyd (James); M. Fornage (Myriam); Gao, H. (He); A. Greinacher (Andreas); V. Gudnason (Vilmundur); T. Hansen (T.); T.B. Harris (Tamara); C. Hayward (Caroline); Hernesniemi, J. (Jussi); H. Highland (Heather); J.N. Hirschhorn (Joel); Hofman, A. (Albert); Irvin, M.R. (Marguerite R.); M. Kähönen (Mika); E.M. Lange (Ethan); Launer, L.J. (Lenore J.); T. Lehtimäki (Terho); Li, J. (Jin); D.C. Liewald (David C.); A. Linneberg (Allan); Y. Liu (YongMei); Y. Lu (Yingchang); L.-P. Lyytikäinen (Leo-Pekka); R. Mägi (Reedik); J. Mathias (Jasmine); O. Melander (Olle); A. Metspalu (Andres); K. Mononen (Kari); M.A. Nalls (Michael); D.A. Nickerson (Deborah); K. Nikus (Kjell); C.J. O'Donnell (Christopher); M. Orho-Melander (Marju); O. Pedersen (Oluf); A. Petersmann (Astrid); Polfus, L. (Linda); B.M. Psaty (Bruce); O.T. Raitakari (Olli T.); Raitoharju, E. (Emma); Richard, M. (Melissa); K.M. Rice (Kenneth); F. Rivadeneira Ramirez (Fernando); Rotter, J.I. (Jerome I.); Schmidt, F. (Frank); A.V. Smith (Albert Vernon); J.M. Starr (John); K.D. Taylor (Kent); A. Teumer (Alexander); Thuesen, B.H. (Betina H.); Torstenson, E.S. (Eric S.); R.P. Tracy (Russell); I. Tzoulaki; N.A. Zakai (Neil); Vacchi-Suzzi, C. (Caterina); C.M. van Duijn (Cornelia); F.J.A. van Rooij (Frank); M. Cushman (Mary Ann); I.J. Deary (Ian J.); Velez Edwards, D.R. (Digna R.); Vergnaud, A.-C. (Anne-Claire); L.C. Wallentin (Lars); D. Waterworth (Dawn); White, H.D. (Harvey D.); J.F. Wilson (James); A.B. Zonderman; S. Kathiresan (Sekar); N. Grarup (Niels); T. Esko (Tõnu); R.J.F. Loos (Ruth); L.A. Lange (Leslie); Faraday, N. (Nauder); Abumrad, N.A. (Nada A.); T.L. Edwards (Todd L.); S.K. Ganesh (Santhi); P. Auer (Paul); A.D. Johnson (Andrew); A. Reiner (Alexander); G. Lettre (Guillaume)

    2016-01-01

    textabstractRed blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an

  17. Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

    DEFF Research Database (Denmark)

    Chami, Nathalie; Chen, Ming-Huei; Slater, Andrew J

    2016-01-01

    Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome ar...

  18. Identifying the Types of Student and Teacher Behaviours Associated with Teacher Stress

    Science.gov (United States)

    Geving, Allison M.

    2007-01-01

    The objectives of this study were to identify the student behaviours associated with teacher stress and determine the types of teacher behaviours that may elicit these stressful student behaviours. Student teachers (n = 186) and their supervising teachers (n = 77) completed a stressful student behaviour questionnaire, a teacher behaviour…

  19. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

    NARCIS (Netherlands)

    Trynka, Gosia; Hunt, Karen A.; Bockett, Nicholas A.; Romanos, Jihane; Mistry, Vanisha; Szperl, Agata; Bakker, Sjoerd F.; Bardella, Maria Teresa; Bhaw-Rosun, Leena; Castillejo, Gemma; de la Concha, Emilio G.; de Almeida, Rodrigo Coutinho; Dias, Kerith-Rae M.; van Diemen, Cleo C.; Dubois, Patrick C. A.; Duerr, Richard H.; Edkins, Sarah; Franke, Lude; Fransen, Karin; Gutierrez, Javier; Heap, Graham A. R.; Hrdlickova, Barbara; Hunt, Sarah; Plaza Izurieta, Leticia; Izzo, Valentina; Joosten, Leo A. B.; Langford, Cordelia; Mazzilli, Maria Cristina; Mein, Charles A.; Midah, Vandana; Mitrovic, Mitja; Mora, Barbara; Morelli, Marinita; Nutland, Sarah; Nunez, Concepcion; Onengut-Gumuscu, Suna; Pearce, Kerra; Platteel, Mathieu; Polanco, Isabel; Potter, Simon; Ribes-Koninckx, Carmen; Ricano-Ponce, Isis; Rich, Stephen S.; Rybak, Anna; Luis Santiago, Jose; Senapati, Sabyasachi; Sood, Ajit; Szajewska, Hania; Troncone, Riccardo; Varade, Jezabel; Wallace, Chris; Wolters, Victorien M.; Zhernakova, Alexandra; Thelma, B. K.; Cukrowska, Bozena; Urcelay, Elena; Ramon Bilbao, Jose; Mearin, M. Luisa; Barisani, Donatella; Barrett, Jeffrey C.; Plagnol, Vincent; Deloukas, Panos; Wijmenga, Cisca; van Heel, David A.

    2011-01-01

    Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified

  20. Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Olama, Ali Amin Al; Giles, Graham G

    2011-01-01

    Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of st...

  1. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N.J. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.-R. Jarvelin (Marjo-Riitta); A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the

  2. Large-scale association analysis identifies new risk loci for coronary artery disease

    NARCIS (Netherlands)

    Deloukas, Panos; Kanoni, Stavroula; Willenborg, Christina; Farrall, Martin; Assimes, Themistocles L.; Thompson, John R.; Ingelsson, Erik; Saleheen, Danish; Erdmann, Jeanette; Goldstein, Benjamin A.; Stirrups, Kathleen; König, Inke R.; Cazier, Jean-Baptiste; Johansson, Asa; Hall, Alistair S.; Lee, Jong-Young; Willer, Cristen J.; Chambers, John C.; Esko, Tõnu; Folkersen, Lasse; Goel, Anuj; Grundberg, Elin; Havulinna, Aki S.; Ho, Weang K.; Hopewell, Jemma C.; Eriksson, Niclas; Kleber, Marcus E.; Kristiansson, Kati; Lundmark, Per; Lyytikäinen, Leo-Pekka; Rafelt, Suzanne; Shungin, Dmitry; Strawbridge, Rona J.; Thorleifsson, Gudmar; Tikkanen, Emmi; van Zuydam, Natalie; Voight, Benjamin F.; Waite, Lindsay L.; Zhang, Weihua; Ziegler, Andreas; Absher, Devin; Altshuler, David; Balmforth, Anthony J.; Barroso, Inês; Braund, Peter S.; Burgdorf, Christof; Claudi-Boehm, Simone; Cox, David; Dimitriou, Maria; Do, Ron; Doney, Alex S. F.; El Mokhtari, NourEddine; Eriksson, Per; Fischer, Krista; Fontanillas, Pierre; Franco-Cereceda, Anders; Gigante, Bruna; Groop, Leif; Gustafsson, Stefan; Hager, Jörg; Hallmans, Göran; Han, Bok-Ghee; Hunt, Sarah E.; Kang, Hyun M.; Illig, Thomas; Kessler, Thorsten; Knowles, Joshua W.; Kolovou, Genovefa; Kuusisto, Johanna; Langenberg, Claudia; Langford, Cordelia; Leander, Karin; Lokki, Marja-Liisa; Lundmark, Anders; McCarthy, Mark I.; Meisinger, Christa; Melander, Olle; Mihailov, Evelin; Maouche, Seraya; Morris, Andrew D.; Müller-Nurasyid, Martina; Nikus, Kjell; Peden, John F.; Rayner, N. William; Rasheed, Asif; Rosinger, Silke; Rubin, Diana; Rumpf, Moritz P.; Schäfer, Arne; Sivananthan, Mohan; Song, Ci; Stewart, Alexandre F. R.; Tan, Sian-Tsung; Thorgeirsson, Gudmundur; van der Schoot, C. Ellen; Wagner, Peter J.; Wells, George A.; Wild, Philipp S.; Yang, Tsun-Po; Amouyel, Philippe; Arveiler, Dominique; Basart, Hanneke; Boehnke, Michael; Boerwinkle, Eric; Brambilla, Paolo; Cambien, Francois; Cupples, Adrienne L.; de Faire, Ulf; Dehghan, Abbas; Diemert, Patrick; Epstein, Stephen E.; Evans, Alun; Ferrario, Marco M.; Ferrières, Jean; Gauguier, Dominique; Go, Alan S.; Goodall, Alison H.; Gudnason, Villi; Hazen, Stanley L.; Holm, Hilma; Iribarren, Carlos; Jang, Yangsoo; Kähönen, Mika; Kee, Frank; Kim, Hyo-Soo; Klopp, Norman; Koenig, Wolfgang; Kratzer, Wolfgang; Kuulasmaa, Kari; Laakso, Markku; Laaksonen, Reijo; Lee, Ji-Young; Lind, Lars; Ouwehand, Willem H.; Parish, Sarah; Park, Jeong E.; Pedersen, Nancy L.; Peters, Annette; Quertermous, Thomas; Rader, Daniel J.; Salomaa, Veikko; Schadt, Eric; Shah, Svati H.; Sinisalo, Juha; Stark, Klaus; Stefansson, Kari; Trégouët, David-Alexandre; Virtamo, Jarmo; Wallentin, Lars; Wareham, Nicholas; Zimmermann, Martina E.; Nieminen, Markku S.; Hengstenberg, Christian; Sandhu, Manjinder S.; Pastinen, Tomi; Syvänen, Ann-Christine; Hovingh, G. Kees; Dedoussis, George; Franks, Paul W.; Lehtimäki, Terho; Metspalu, Andres; Zalloua, Pierre A.; Siegbahn, Agneta; Schreiber, Stefan; Ripatti, Samuli; Blankenberg, Stefan S.; Perola, Markus; Clarke, Robert; Boehm, Bernhard O.; O'Donnell, Christopher; Reilly, Muredach P.; März, Winfried; Collins, Rory; Kathiresan, Sekar; Hamsten, Anders; Kooner, Jaspal S.; Thorsteinsdottir, Unnur; Danesh, John; Palmer, Colin N. A.; Roberts, Robert; Watkins, Hugh; Schunkert, Heribert; Samani, Nilesh J.

    2013-01-01

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2)

  3. IMA: Identifying disease-related genes using MeSH terms and association rules.

    Science.gov (United States)

    Kim, Jeongwoo; Bang, Changbae; Hwang, Hyeonseo; Kim, Doyoung; Park, Chihyun; Park, Sanghyun

    2017-12-01

    Genes play an important role in several diseases. Hence, in biology, identifying relationships between diseases and genes is important for the analysis of diseases, because mutated or dysregulated genes play an important role in pathogenesis. Here, we propose a method to identify disease-related genes using MeSH terms and association rules. We identified genes by analyzing the MeSH terms and extracted information on gene-gene interactions based on association rules. By integrating the extracted interactions, we constructed gene-gene networks and identified disease-related genes. We applied the proposed method to study five cancers, including prostate, lung, breast, stomach, and colorectal cancer, and demonstrated that the proposed method is more useful for identifying disease-related and candidate disease-related genes than previously published methods. In this study, we identified 20 genes for each disease. Among them, we presented 34 important candidate genes with evidence that supports the relationship of the candidate genes with diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lindgren

    2009-06-01

    Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  5. Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

    Science.gov (United States)

    Qi, Lu; Speliotes, Elizabeth K.; Thorleifsson, Gudmar; Willer, Cristen J.; Herrera, Blanca M.; Jackson, Anne U.; Lim, Noha; Scheet, Paul; Soranzo, Nicole; Amin, Najaf; Aulchenko, Yurii S.; Chambers, John C.; Drong, Alexander; Luan, Jian'an; Lyon, Helen N.; Rivadeneira, Fernando; Sanna, Serena; Timpson, Nicholas J.; Zillikens, M. Carola; Zhao, Jing Hua; Almgren, Peter; Bandinelli, Stefania; Bennett, Amanda J.; Bergman, Richard N.; Bonnycastle, Lori L.; Bumpstead, Suzannah J.; Chanock, Stephen J.; Cherkas, Lynn; Chines, Peter; Coin, Lachlan; Cooper, Cyrus; Crawford, Gabriel; Doering, Angela; Dominiczak, Anna; Doney, Alex S. F.; Ebrahim, Shah; Elliott, Paul; Erdos, Michael R.; Estrada, Karol; Ferrucci, Luigi; Fischer, Guido; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Groves, Christopher J.; Grundy, Scott; Guiducci, Candace; Hadley, David; Hamsten, Anders; Havulinna, Aki S.; Hofman, Albert; Holle, Rolf; Holloway, John W.; Illig, Thomas; Isomaa, Bo; Jacobs, Leonie C.; Jameson, Karen; Jousilahti, Pekka; Karpe, Fredrik; Kuusisto, Johanna; Laitinen, Jaana; Lathrop, G. Mark; Lawlor, Debbie A.; Mangino, Massimo; McArdle, Wendy L.; Meitinger, Thomas; Morken, Mario A.; Morris, Andrew P.; Munroe, Patricia; Narisu, Narisu; Nordström, Anna; Nordström, Peter; Oostra, Ben A.; Palmer, Colin N. A.; Payne, Felicity; Peden, John F.; Prokopenko, Inga; Renström, Frida; Ruokonen, Aimo; Salomaa, Veikko; Sandhu, Manjinder S.; Scott, Laura J.; Scuteri, Angelo; Silander, Kaisa; Song, Kijoung; Yuan, Xin; Stringham, Heather M.; Swift, Amy J.; Tuomi, Tiinamaija; Uda, Manuela; Vollenweider, Peter; Waeber, Gerard; Wallace, Chris; Walters, G. Bragi; Weedon, Michael N.; Witteman, Jacqueline C. M.; Zhang, Cuilin; Zhang, Weihua; Caulfield, Mark J.; Collins, Francis S.; Davey Smith, George; Day, Ian N. M.; Franks, Paul W.; Hattersley, Andrew T.; Hu, Frank B.; Jarvelin, Marjo-Riitta; Kong, Augustine; Kooner, Jaspal S.; Laakso, Markku; Lakatta, Edward; Mooser, Vincent; Morris, Andrew D.; Peltonen, Leena; Samani, Nilesh J.; Spector, Timothy D.; Strachan, David P.; Tanaka, Toshiko; Tuomilehto, Jaakko; Uitterlinden, André G.; van Duijn, Cornelia M.; Wareham, Nicholas J.; Watkins for the PROCARDIS consortia, Hugh; Waterworth, Dawn M.; Boehnke, Michael; Deloukas, Panos; Groop, Leif; Hunter, David J.; Thorsteinsdottir, Unnur; Schlessinger, David; Wichmann, H.-Erich; Frayling, Timothy M.; Abecasis, Gonçalo R.; Hirschhorn, Joel N.; Loos, Ruth J. F.; Stefansson, Kari; Mohlke, Karen L.; Barroso, Inês; McCarthy for the GIANT consortium, Mark I.

    2009-01-01

    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist–hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×10−11) and MSRA (WC, P = 8.9×10−9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10−8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity. PMID:19557161

  6. 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.

  7. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo

    Science.gov (United States)

    Jin, Ying; Birlea, Stanca A; Fain, Pamela R; Ferrara, Tracey M; Ben, Songtao; Riccardi, Sheri L; Cole, Joanne B; Gowan, Katherine; Holland, Paulene J; Bennett, Dorothy C; Luiten, Rosalie M; Wolkerstorfer, Albert; van der Veen, JP Wietze; Hartmann, Anke; Eichner, Saskia; Schuler, Gerold; van Geel, Nanja; Lambert, Jo; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Taïeb, Alain; Jouary, Thomas; Ezzedine, Khaled; Wallace, Margaret R; McCormack, Wayne T; Picardo, Mauro; Leone, Giovanni; Overbeck, Andreas; Silverberg, Nanette B; Spritz, Richard A

    2012-01-01

    In previous linkage and genome-wide association studies we identified 17 susceptibility loci for generalized vitiligo. By a second genome-wide association study, meta-analysis, and independent replication study, we have now identified 13 additional vitiligo-associated loci, including OCA2-HERC2, a region of 16q24.3 containing MC1R, a region of chromosome 11q21 near TYR, several immunoregulatory loci including IFIH1, CD80, CLNK, BACH2, SLA, CASP7, CD44, IKZF4, SH2B3, and a region of 22q13.2 where the causal gene remains uncertain. Functional pathway analysis shows that most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and genetic relationships among vitiligo, malignant melanoma, and normal variation of eye, skin, and hair color. PMID:22561518

  8. Proteomic profiling of human plasma exosomes identifies PPARγ as an exosome-associated protein

    International Nuclear Information System (INIS)

    Looze, Christopher; Yui, David; Leung, Lester; Ingham, Matthew; Kaler, Maryann; Yao, Xianglan; Wu, Wells W.; Shen Rongfong; Daniels, Mathew P.; Levine, Stewart J.

    2009-01-01

    Exosomes are nanovesicles that are released from cells as a mechanism of cell-free intercellular communication. Only a limited number of proteins have been identified from the plasma exosome proteome. Here, we developed a multi-step fractionation scheme incorporating gel exclusion chromatography, rate zonal centrifugation through continuous sucrose gradients, and high-speed centrifugation to purify exosomes from human plasma. Exosome-associated proteins were separated by SDS-PAGE and 66 proteins were identified by LC-MS/MS, which included both cellular and extracellular proteins. Furthermore, we identified and characterized peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor that regulates adipocyte differentiation and proliferation, as well as immune and inflammatory cell functions, as a novel component of plasma-derived exosomes. Given the important role of exosomes as intercellular messengers, the discovery of PPARγ as a component of human plasma exosomes identifies a potential new pathway for the paracrine transfer of nuclear receptors.

  9. The dynamics of competitive activity performance of the strongest athletes in the world during the Olympic year

    Directory of Open Access Journals (Sweden)

    Rabin Muhammad Fahmi

    2016-12-01

    Full Text Available The paper scrutinizes the annual dynamics of competitive activity performance of prize winners in track and field of the Games of the XXXI Olympiad in Rio de Janeiro. The studies performed allow to identify two basic strategies of participation of elite athletes in the competitions. The first implies a strong focus on achieving the best results in major competitions of the year. It is used by most of the strongest athletes in the world. The second focuses the athlete on the effective combination of competitive activity in major competitions of the year (the Olympics and World Championships and in the Diamond League. As shown by the experience of the best sports practice, only a limited number of athletes manage to implement the latter strategy. The methodological approaches to planning competitive activity during the year are identified. The first involves the rational allocation of the optimal number of competitions throughout the year, the second focuses on preparatory competitive activities of a fairly high intensity, and the third involves the use of a small number of competitions in the system of annual training.

  10. Evidence for the strongest version of the 4d a-theorem via a-maximization along RG flows

    International Nuclear Information System (INIS)

    Barnes, Edwin; Intriligator, Ken; Wecht, Brian; Wright, Jason

    2004-01-01

    In earlier work, we (KI and BW) gave a two line 'almost proof' (for supersymmetric RG flows) of the weakest form of the conjectured 4d a-theorem, that aIRaUV, using our result that the exact superconformal R-symmetry of 4d SCFTs maximizes a=3TrR3-TrR. The proof was incomplete because of two identified loopholes: theories with accidental symmetries, and the fact that it is only a local maximum of a. Here we discuss and extend a proposal of Kutasov (which helps close the latter loophole) in which a-maximization is generalized away from the endpoints of the RG flow, with Lagrange multipliers that are conjectured to be identified with the running coupling constants. a-maximization then yields a monotonically decreasing 'a-function' along the RG flow to the IR. As we discuss, this proposal in fact suggests the strongest version of the a-theorem: that 4d RG flows are gradient flows of an a-function, with positive-definite metric. In the perturbative limit, the RG flow metric thus obtained is shown to agree precisely with that found by very different computations by Osborn and collaborators. As examples, we discuss a new class of 4d SCFTs, along with their dual descriptions and IR phases, obtained from SQCD by coupling some of the flavors to added singlets

  11. Identifying dietary patterns and associated health-related lifestyle factors in the adult Danish population

    DEFF Research Database (Denmark)

    Knudsen, Vibeke Kildegaard; Matthiessen, Jeppe; Biltoft-Jensen, Anja Pia

    2014-01-01

    , potatoes and gravy, and cake and biscuits; a 'health-conscious' pattern correlated with coarse bread, fruit, vegetables, low-fat dairy, nuts, water and tea; and a 'fast food' pattern correlated with pizza, hamburger/spring rolls, crisps, rice and pasta, sugar-sweetened soft drinks and sweets....... The 'traditional' pattern was positively associated with male gender and age, whereas the 'health-conscious' pattern was positively associated with being female, increasing age and educational level. The 'fast food' pattern was inversely associated with age and smoking.Conclusions:Three distinct dietary patterns......Background/objectives:To identify and describe dietary patterns in Danish adults and to examine which demographic and health-related lifestyle factors are associated with dietary patterns.Subjects/methods:Data derived from the Danish national survey of diet and physical activity collected in 2003...

  12. Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer.

    LENUS (Irish Health Repository)

    McEvoy, Lynda M

    2015-01-01

    Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance.

  13. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    Science.gov (United States)

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Gonçalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Inês; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I

    2011-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combinedP < 5 × 10−8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. PMID:20581827

  14. Genome-wide association identifies multiple genomic regions associated with susceptibility to and control of ovine lentivirus.

    Directory of Open Access Journals (Sweden)

    Stephen N White

    Full Text Available BACKGROUND: Like human immunodeficiency virus (HIV, ovine lentivirus (OvLV is macrophage-tropic and causes lifelong infection. OvLV infects one quarter of U.S. sheep and induces pneumonia and body condition wasting. There is no vaccine to prevent OvLV infection and no cost-effective treatment for infected animals. However, breed differences in prevalence and proviral concentration have indicated a genetic basis for susceptibility to OvLV. A recent study identified TMEM154 variants in OvLV susceptibility. The objective here was to identify additional loci associated with odds and/or control of OvLV infection. METHODOLOGY/PRINCIPAL FINDINGS: This genome-wide association study (GWAS included 964 sheep from Rambouillet, Polypay, and Columbia breeds with serological status and proviral concentration phenotypes. Analytic models accounted for breed and age, as well as genotype. This approach identified TMEM154 (nominal P=9.2×10(-7; empirical P=0.13, provided 12 additional genomic regions associated with odds of infection, and provided 13 regions associated with control of infection (all nominal P<1 × 10(-5. Rapid decline of linkage disequilibrium with distance suggested many regions included few genes each. Genes in regions associated with odds of infection included DPPA2/DPPA4 (empirical P=0.006, and SYTL3 (P=0.051. Genes in regions associated with control of infection included a zinc finger cluster (ZNF192, ZSCAN16, ZNF389, and ZNF165; P=0.001, C19orf42/TMEM38A (P=0.047, and DLGAP1 (P=0.092. CONCLUSIONS/SIGNIFICANCE: These associations provide targets for mutation discovery in sheep susceptibility to OvLV. Aside from TMEM154, these genes have not been associated previously with lentiviral infection in any species, to our knowledge. Further, data from other species suggest functional hypotheses for future testing of these genes in OvLV and other lentiviral infections. Specifically, SYTL3 binds and may regulate RAB27A, which is required for enveloped

  15. ON POTENTIAL REPRESENTATIONS OF THE DISTRIBUTION LAW OF RARE STRONGEST EARTHQUAKES

    Directory of Open Access Journals (Sweden)

    M. V. Rodkin

    2014-01-01

    Full Text Available Assessment of long-term seismic hazard is critically dependent on the behavior of tail of the distribution function of rare strongest earthquakes. Analyses of empirical data cannot however yield the credible solution of this problem because the instrumental catalogs of earthquake are available only for a rather short time intervals, and the uncertainty in estimations of magnitude of paleoearthquakes is high. From the available data, it was possible only to propose a number of alternative models characterizing the distribution of rare strongest earthquakes. There are the following models: the model based on theGuttenberg – Richter law suggested to be valid until a maximum possible seismic event (Мmах, models of 'bend down' of earthquake recurrence curve, and the characteristic earthquakes model. We discuss these models from the general physical concepts supported by the theory of extreme values (with reference to the generalized extreme value (GEV distribution and the generalized Pareto distribution (GPD and the multiplicative cascade model of seismic regime. In terms of the multiplicative cascade model, seismic regime is treated as a large number of episodes of avalanche-type relaxation of metastable states which take place in a set of metastable sub-systems.The model of magnitude-unlimited continuation of the Guttenberg – Richter law is invalid from the physical point of view because it corresponds to an infinite mean value of seismic energy and infinite capacity of the process generating seismicity. A model of an abrupt cut of this law by a maximum possible event, Мmах is not fully logical either.A model with the 'bend-down' of earthquake recurrence curve can ensure both continuity of the distribution law and finiteness of seismic energy value. Results of studies with the use of the theory of extreme values provide a convincing support to the model of 'bend-down' of earthquakes’ recurrence curve. Moreover they testify also that the

  16. Identifying the role of Wilms tumor 1 associated protein in cancer prediction using integrative genomic analyses.

    Science.gov (United States)

    Wu, Li-Sheng; Qian, Jia-Yi; Wang, Minghai; Yang, Haiwei

    2016-09-01

    The Wilms tumor suppressor, WT1 was first identified due to its essential role in the normal development of the human genitourinary system. Wilms tumor 1 associated protein (WTAP) was subsequently revealed to interact with WT1 using yeast two-hybrid screening. The present study identified 44 complete WTAP genes in the genomes of vertebrates, including fish, amphibians, birds and mammals. The vertebrate WTAP proteins clustered into the primate, rodent and teleost lineages using phylogenetic tree analysis. From 1,347 available SNPs in the human WTAP gene, 19 were identified to cause missense mutations. WTAP was expressed in bladder, blood, brain, breast, colorectal, esophagus, eye, head and neck, lung, ovarian, prostate, skin and soft tissue cancers. A total of 17 out of 328 microarrays demonstrated an association between WTAP gene expression and cancer prognosis. However, the association between WTAP gene expression and prognosis varied in distinct types of cancer, and even in identical types of cancer from separate microarray databases. By searching the Catalogue of Somatic Mutations in Cancer database, 65 somatic mutations were identified in the human WTAP gene from the cancer tissue samples. These results suggest that the function of WTAP in tumor formation may be multidimensional. Furthermore, signal transducer and activator of transcription 1, forkhead box protein O1, interferon regulatory factor 1, glucocorticoid receptor and peroxisome proliferator-activated receptor γ transcription factor binding sites were identified in the upstream (promoter) region of the human WTAP gene, suggesting that these transcription factors may be involved in WTAP functions in tumor formation.

  17. Genome-wide association study identifies novel breast cancer susceptibility loci

    OpenAIRE

    Easton, Douglas F.; Pooley, Karen A.; Dunning, Alison M.; Pharoah, Paul D. P.; Thompson, Deborah; Ballinger, Dennis G.; Struewing, Jeffery P.; Morrison, Jonathan; Field, Helen; Luben, Robert; Wareham, Nicholas; Ahmed, Shahana; Healey, Catherine S.; Bowman, Richard; Meyer, Kerstin B.

    2007-01-01

    Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single n...

  18. Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.

    Directory of Open Access Journals (Sweden)

    Carsten A Böger

    2011-09-01

    Full Text Available Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD and end stage renal disease (ESRD. Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m(2 at follow-up and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls. SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1. SNPs in UMOD (OR = 0.92, p = 0.04 and GCKR (OR = 0.93, p = 0.03 were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.

  19. FACTORS ASSOCIATED WITH STROKE SURVIVOR BEHAVIORS AS IDENTIFIED BY FAMILY CAREGIVERS

    Science.gov (United States)

    Gonzalez, Carmanny; Bakas, Tamilyn

    2013-01-01

    Stroke survivor behaviors that caregivers identify as bothersome can lead to family caregiver stress, which can result in premature institutionalization of the survivor. The purpose of this study was to explore demographic and theory-based factors associated with survivor bothersome behaviors as identified by family caregivers. A secondary analysis of a combined sample of 96 family caregivers of stroke survivors was conducted using baseline data from 2 existing studies. Bothersome behaviors were measured using the Revised Memory and Behavior Problems Checklist (RMBPC). Theory-based factors were measured using well-validated scales. Male stroke survivors exhibited more bothersome behaviors (t = 3.53, p nursing interventions designed to reduce bothersome behaviors as identified by family caregivers. PMID:23686515

  20. Identifying factors associated with the discharge of male State patients from Weskoppies Hospital

    Directory of Open Access Journals (Sweden)

    Riaan G. Prinsloo

    2017-12-01

    Full Text Available Background: Designated psychiatric facilities are responsible for the care, treatment and reintegration of State patients. The necessary long-term care places a considerable strain on health-care resources. Resource use should be optimised while managing the risks that patients pose to themselves and the community. Identifying unique factors associated with earlier discharge may decrease the length of stay. Factors associated with protracted inpatient care without discharge could identify patients who require early and urgent intervention. Aim: We identify socio-economic, demographic, psychiatric and charge-related factors associated with the discharge of male State patients. Methods: We reviewed the files of discharged and admitted forensic State patients at Weskoppies Psychiatric Hospital. Data were captured in an electronic recording sheet. The association between factors and the outcome measure (discharged vs. admitted was determined using chi-squared tests and Fischer’s exact tests. Results: Discharged State patients were associated with being a primary caregiver (p = 0.031 having good insight into illness (p = 0.025 or offence (p = 0.005 and having had multiple successful leaves of absences. A lack of substance abuse during admission (p = 0.027, an absence of a diagnosis of substance use disorder (p = 0.013 and the absence of verbal and physical aggression (p = 0.002 and p = 0.016 were associated with being discharged. Prolonged total length of stay (9–12 years, p = 0.031 and prolonged length of stay in open wards (6–9 years, p = 0.000 were associated with being discharged. A history of previous offences (p = 0.022, a diagnosis of substance use disorder (p = 0.023, recent substance abuse (p = 0.018 and a history of physical aggression since admission (p = 0.017 were associated with continued admission. Conclusion: Discharge of State patients is associated with an absence of substance abuse, lack of aggression

  1. Large scale association analysis identifies three susceptibility loci for coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Stephanie Saade

    Full Text Available Genome wide association studies (GWAS and their replications that have associated DNA variants with myocardial infarction (MI and/or coronary artery disease (CAD are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3, and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035, while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086. Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.

  2. Screen and clean: a tool for identifying interactions in genome-wide association studies.

    Science.gov (United States)

    Wu, Jing; Devlin, Bernie; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn

    2010-04-01

    Epistasis could be an important source of risk for disease. How interacting loci might be discovered is an open question for genome-wide association studies (GWAS). Most researchers limit their statistical analyses to testing individual pairwise interactions (i.e., marginal tests for association). A more effective means of identifying important predictors is to fit models that include many predictors simultaneously (i.e., higher-dimensional models). We explore a procedure called screen and clean (SC) for identifying liability loci, including interactions, by using the lasso procedure, which is a model selection tool for high-dimensional regression. We approach the problem by using a varying dictionary consisting of terms to include in the model. In the first step the lasso dictionary includes only main effects. The most promising single-nucleotide polymorphisms (SNPs) are identified using a screening procedure. Next the lasso dictionary is adjusted to include these main effects and the corresponding interaction terms. Again, promising terms are identified using lasso screening. Then significant terms are identified through the cleaning process. Implementation of SC for GWAS requires algorithms to explore the complex model space induced by the many SNPs genotyped and their interactions. We propose and explore a set of algorithms and find that SC successfully controls Type I error while yielding good power to identify risk loci and their interactions. When the method is applied to data obtained from the Wellcome Trust Case Control Consortium study of Type 1 Diabetes it uncovers evidence supporting interaction within the HLA class II region as well as within Chromosome 12q24.

  3. Genome-wide association study to identify common variants associated with brachial circumference: a meta-analysis of 14 cohorts.

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    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.

  4. Biomedical application of fuzzy association rules for identifying breast cancer biomarkers.

    Science.gov (United States)

    Lopez, F J; Cuadros, M; Cano, C; Concha, A; Blanco, A

    2012-09-01

    Current breast cancer research involves the study of many different prognosis factors: primary tumor size, lymph node status, tumor grade, tumor receptor status, p53, and ki67 levels, among others. High-throughput microarray technologies are allowing to better understand and identify prognostic factors in breast cancer. But the massive amounts of data derived from these technologies require the use of efficient computational techniques to unveil new and relevant biomedical knowledge. Furthermore, integrative tools are needed that effectively combine heterogeneous types of biomedical data, such as prognosis factors and expression data. The objective of this study was to integrate information from the main prognostic factors in breast cancer with whole-genome microarray data to identify potential associations among them. We propose the application of a data mining approach, called fuzzy association rule mining, to automatically unveil these associations. This paper describes the proposed methodology and illustrates how it can be applied to different breast cancer datasets. The obtained results support known associations involving the number of copies of chromosome-17, HER2 amplification, or the expression level of estrogen and progesterone receptors in breast cancer patients. They also confirm the correspondence between the HER2 status predicted by different testing methodologies (immunohistochemistry and fluorescence in situ hybridization). In addition, other interesting rules involving CDC6, SOX11, and EFEMP1 genes are identified, although further detailed studies are needed to statistically confirm these findings. As part of this study, a web platform implementing the fuzzy association rule mining approach has been made freely available at: http://www.genome2.ugr.es/biofar .

  5. Genome-wide association study identifies three common variants associated with serologic response to vitamin E supplementation in men.

    Science.gov (United States)

    Major, Jacqueline M; Yu, Kai; Chung, Charles C; Weinstein, Stephanie J; Yeager, Meredith; Wheeler, William; Snyder, Kirk; Wright, Margaret E; Virtamo, Jarmo; Chanock, Stephen; Albanes, Demetrius

    2012-05-01

    Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating α-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of α-tocopherol (50 mg/d) and had fasting serum α-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to α-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P = 2.6 × 10(-12)) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10(-7)), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10(-7)). Combined, these SNP explain 3.4% of the residual variance in serum α-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.

  6. Association rules to identify complications of cerebral infarction in patients with atrial fibrillation.

    Science.gov (United States)

    Jung, Sun-Ju; Son, Chang-Sik; Kim, Min-Soo; Kim, Dae-Joon; Park, Hyoung-Seob; Kim, Yoon-Nyun

    2013-03-01

    The purpose of this study was to find risk factors that are associated with complications of cerebral infarction in patients with atrial fibrillation (AF) and to discover useful association rules among these factors. The risk factors with respect to cerebral infarction were selected using logistic regression analysis with the Wald's forward selection approach. The rules to identify the complications of cerebral infarction were obtained by using the association rule mining (ARM) approach. We observed that 4 independent factors, namely, age, hypertension, initial electrocardiographic rhythm, and initial echocardiographic left atrial dimension (LAD), were strong predictors of cerebral infarction in patients with AF. After the application of ARM, we obtained 4 useful rules to identify complications of cerebral infarction: age (>63 years) and hypertension (Yes) and initial ECG rhythm (AF) and initial Echo LAD (>4.06 cm); age (>63 years) and hypertension (Yes) and initial Echo LAD (>4.06 cm); hypertension (Yes) and initial ECG rhythm (AF) and initial Echo LAD (>4.06 cm); age (>63 years) and hypertension (Yes) and initial ECG rhythm (AF). Among the induced rules, 3 factors (the initial ECG rhythm [i.e., AF], initial Echo LAD, and age) were strongly associated with each other.

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

    Science.gov (United States)

    Fatemifar, Ghazaleh; Hoggart, Clive J; Paternoster, Lavinia; Kemp, John P; Prokopenko, Inga; Horikoshi, Momoko; Wright, Victoria J; Tobias, Jon H; Richmond, Stephen; Zhurov, Alexei I; Toma, Arshed M; Pouta, Anneli; Taanila, Anja; Sipila, Kirsi; Lähdesmäki, Raija; Pillas, Demetris; Geller, Frank; Feenstra, Bjarke; Melbye, Mads; Nohr, Ellen A; Ring, Susan M; St Pourcain, Beate; Timpson, Nicholas J; Davey Smith, George; Jarvelin, Marjo-Riitta; Evans, David M

    2013-09-15

    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 and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P tooth' and 11 loci for 'number of teeth'. Together, these associations explain 6.06% of the variation in 'age of first tooth' and 4.76% of the variation in 'number of teeth'. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including an SNP in the protein-coding region of BMP4 (rs17563, P = 9.080 × 10(-17)). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development.

  8. Annona muricata leaves have strongest cytotoxic activity against breast cancer cells

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    Susi Endrini

    2014-12-01

    Full Text Available Background Plant-derived herbal compounds have a long history of clinical use, better patient tolerance and acceptance. They are freely available natural compounds that can be safely used to prevent various ailments. Plants have been the basis of traditional medicine throughout the world for thousands of years and are providing mankind with new remedies. The objective of this study was to determine the cytotoxicity of soursop (Anona muricata Linn leaves and pearl grass (Hedyotis corymbosa (L. Lam. on the hormone-dependent human breast carcinoma Michigan Cancer Foundation-7 (MCF-7 cell line. Methods This study used two types of solvents (water and ethanol in the extraction process and two incubation times (24 hours and 48 hours in the MTT assays to analyze the cytotoxic effects of both plants. Results Preliminary results showed that the ethanolic extract of soursop leaves (SE displayed cytotoxic effects against MCF-7 on 24- and 48-hour incubation times with IC50 values of 88.788 ìg/ml and 14.678 mg/ml, respectively. Ethanolic pearl grass extract (PE showed similar results, with IC50 values of 65.011 mg/ml on 24-hour incubation time and 52.329 mg/ml on 48-hour incubation time against MCF-7 cell line. However, the water extract of both plants displayed lower cytotoxic effect against MCF-7 cell line. Conclusion The ethanolic extract of both plants displayed cytotoxic effect against MCF-7. Soursop (Anona muricata Linn leaves have the strongest cytotoxic activity against MCF-7 breast cancer cell line.

  9. Annona muricata leaves have strongest cytotoxic activity against breast cancer cells

    Directory of Open Access Journals (Sweden)

    Susi Endrini

    2015-12-01

    Full Text Available BACKGROUND Plant-derived herbal compounds have a long history of clinical use, better patient tolerance and acceptance. They are freely available natural compounds that can be safely used to prevent various ailments. Plants have been the basis of traditional medicine throughout the world for thousands of years and are providing mankind with new remedies. The objective of this study was to determine the cytotoxicity of soursop (Anona muricata Linn leaves and pearl grass (Hedyotis corymbosa (L. Lam. on the hormone-dependent human breast carcinoma Michigan Cancer Foundation-7 (MCF-7 cell line. METHODS This study used two types of solvents (water and ethanol in the extraction process and two incubation times (24 hours and 48 hours in the MTT assays to analyze the cytotoxic effects of both plants. RESULTS Preliminary results showed that the ethanolic extract of soursop leaves (SE displayed cytotoxic effects against MCF-7 on 24- and 48-hour incubation times with IC50 values of 88.788 μg/ml and 14.678 μg/ml, respectively. Ethanolic pearl grass extract (PE showed similar results, with IC50 values of 65.011 μg/ ml on 24-hour incubation time and 52.329 μg/ml on 48-hour incubation time against MCF-7 cell line. However, the water extract of both plants displayed lower cytotoxic effect against MCF-7 cell line. CONCLUSION The ethanolic extract of both plants displayed cytotoxic effect against MCF-7. Soursop (Anona muricata Linn leaves have the strongest cytotoxic activity against MCF-7 breast cancer cell line.

  10. Timed Stair Climbing is the Single Strongest Predictor of Perioperative Complications in Patients Undergoing Abdominal Surgery

    Science.gov (United States)

    Reddy, Sushanth; Contreras, Carlo M; Singletary, Brandon; Bradford, T Miller; Waldrop, Mary G; Mims, Andrew H; Smedley, W Andrew; Swords, Jacob A; Thomas N, Wang; Martin J, Heslin

    2016-01-01

    Background Current methods to predict patients' peri-operative morbidity utilize complex algorithms with multiple clinical variables focusing primarily on organ-specific compromise. The aim of the present study is to determine the value of a timed stair climb (SC) in predicting peri-operative complications for patients undergoing abdominal surgery. Study Design From March 2014 to July 2015, 362 patients attempted SC while being timed prior to undergoing elective abdominal surgery. Vital signs were measured before and after SC. Ninety day post-operative complications were assessed by the Accordion Severity Grading System. The prognostic value of SC was compared to the ACS NSQIP risk calculator. Results A total of 264 (97.4%) patients were able to complete SC. SC time directly correlated to changes in both mean arterial pressure and heart rate as an indicator of stress. An Accordion grade 2 or higher complication occurred in 84 (25%) patients. There were 8 mortalities (2.4%). Patients with slower SC times had an increased complication rate (P<0.0001). In multivariable analysis SC time was the single strongest predictor of complications (OR=1.029, P<0.0001), and no other clinical co-morbidity reached statistical significance. Receiver operative characteristic curves predicting post-operative morbidity by SC time was superior to that of the ACS risk calculator (AUC 0.81 vs. 0.62, P<0.0001). Additionally slower patients had a greater deviation from predicted length of hospital stay (P=0.034) Conclusions SC provides measurable stress, accurately predicts post-operative complications, and is easy to administer in patients undergoing abdominal surgery. Larger patient populations with a diverse group of operations will be needed to further validate the use of SC in risk prediction models. PMID:26920993

  11. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor.

    Science.gov (United States)

    Wang, Zhaoming; McGlynn, Katherine A; Rajpert-De Meyts, Ewa; Bishop, D Timothy; Chung, Charles C; Dalgaard, Marlene D; Greene, Mark H; Gupta, Ramneek; Grotmol, Tom; Haugen, Trine B; Karlsson, Robert; Litchfield, Kevin; Mitra, Nandita; Nielsen, Kasper; Pyle, Louise C; Schwartz, Stephen M; Thorsson, Vésteinn; Vardhanabhuti, Saran; Wiklund, Fredrik; Turnbull, Clare; Chanock, Stephen J; Kanetsky, Peter A; Nathanson, Katherine L

    2017-07-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 × 10 -8 ). Most loci harbor biologically plausible candidate genes. We refined previously reported associations at 9p24.3 and 19p12 by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son familial risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT susceptibility alleles, move the field closer to a comprehensive understanding of the underlying genetic architecture of TGCT, and provide further clues to the etiology of TGCT.

  12. Genome-wide association study identifies a novel canine glaucoma locus.

    Directory of Open Access Journals (Sweden)

    Saija J Ahonen

    Full Text Available Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG, primary open-angle (POAG and primary congenital glaucoma (PCG. Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT in which it is a late-onset (>7 years disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63 × 10(-10, OR = 32 for homozygosity. Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease.

  13. A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease

    Science.gov (United States)

    Breunis, Willemijn B.; Ng, Sarah B.; Li, Yi; Bonnard, Carine; Ling, Ling; Wright, Victoria J.; Thalamuthu, Anbupalam; Odam, Miranda; Shimizu, Chisato; Burns, Jane C.; Levin, Michael; Kuijpers, Taco W.; Hibberd, Martin L.

    2009-01-01

    Kawasaki disease (KD) is a pediatric vasculitis that damages the coronary arteries in 25% of untreated and approximately 5% of treated children. Epidemiologic data suggest that KD is triggered by unidentified infection(s) in genetically susceptible children. To investigate genetic determinants of KD susceptibility, we performed a genome-wide association study (GWAS) in 119 Caucasian KD cases and 135 matched controls with stringent correction for possible admixture, followed by replication in an independent cohort and subsequent fine-mapping, for a total of 893 KD cases plus population and family controls. Significant associations of 40 SNPs and six haplotypes, identifying 31 genes, were replicated in an independent cohort of 583 predominantly Caucasian KD families, with NAALADL2 (rs17531088, p combined = 1.13×10−6) and ZFHX3 (rs7199343, p combined = 2.37×10−6) most significantly associated. Sixteen associated variants with a minor allele frequency of >0.05 that lay within or close to known genes were fine-mapped with HapMap tagging SNPs in 781 KD cases, including 590 from the discovery and replication stages. Original or tagging SNPs in eight of these genes replicated the original findings, with seven genes having further significant markers in adjacent regions. In four genes (ZFHX3, NAALADL2, PPP1R14C, and TCP1), the neighboring markers were more significantly associated than the originally associated variants. Investigation of functional relationships between the eight fine-mapped genes using Ingenuity Pathway Analysis identified a single functional network (p = 10−13) containing five fine-mapped genes—LNX1, CAMK2D, ZFHX3, CSMD1, and TCP1—with functional relationships potentially related to inflammation, apoptosis, and cardiovascular pathology. Pair-wise blood transcript levels were measured during acute and convalescent KD for all fine-mapped genes, revealing a consistent trend of significantly reduced transcript levels prior to treatment

  14. A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease.

    Directory of Open Access Journals (Sweden)

    David Burgner

    2009-01-01

    Full Text Available Kawasaki disease (KD is a pediatric vasculitis that damages the coronary arteries in 25% of untreated and approximately 5% of treated children. Epidemiologic data suggest that KD is triggered by unidentified infection(s in genetically susceptible children. To investigate genetic determinants of KD susceptibility, we performed a genome-wide association study (GWAS in 119 Caucasian KD cases and 135 matched controls with stringent correction for possible admixture, followed by replication in an independent cohort and subsequent fine-mapping, for a total of 893 KD cases plus population and family controls. Significant associations of 40 SNPs and six haplotypes, identifying 31 genes, were replicated in an independent cohort of 583 predominantly Caucasian KD families, with NAALADL2 (rs17531088, p(combined = 1.13 x 10(-6 and ZFHX3 (rs7199343, p(combined = 2.37 x 10(-6 most significantly associated. Sixteen associated variants with a minor allele frequency of >0.05 that lay within or close to known genes were fine-mapped with HapMap tagging SNPs in 781 KD cases, including 590 from the discovery and replication stages. Original or tagging SNPs in eight of these genes replicated the original findings, with seven genes having further significant markers in adjacent regions. In four genes (ZFHX3, NAALADL2, PPP1R14C, and TCP1, the neighboring markers were more significantly associated than the originally associated variants. Investigation of functional relationships between the eight fine-mapped genes using Ingenuity Pathway Analysis identified a single functional network (p = 10(-13 containing five fine-mapped genes-LNX1, CAMK2D, ZFHX3, CSMD1, and TCP1-with functional relationships potentially related to inflammation, apoptosis, and cardiovascular pathology. Pair-wise blood transcript levels were measured during acute and convalescent KD for all fine-mapped genes, revealing a consistent trend of significantly reduced transcript levels prior to treatment

  15. Factors associated with phyllodes tumor of the breast after core needle biopsy identifies fibroepithelial neoplasm.

    Science.gov (United States)

    Gould, Daniel J; Salmans, Jessica A; Lassinger, Brian K; Contreras, Alejandro; Gutierrez, Carolina; Bonefas, Elizabeth; Liscum, Kathleen R; Silberfein, Eric J

    2012-11-01

    Phyllodes tumors represent less than 1% of all breast neoplasms and can mimic fibroadenoma on core needle biopsy (CNB). The treatment of fibroepithelial (FE) neoplasms identified on CNB is controversial. We sought to identify factors that were associated with phyllodes tumors after CNB suggested FE neoplasm. A retrospective database was queried for all patients diagnosed with FE neoplasm on CNB at Ben Taub General Hospital over a 10-y period. One hundred twenty-three patients were identified and demographic, clinical, and outcome data were analyzed. Of the 123 patients, 46 (37%) were found to have fibroadenomatous features and 59 (48%) were found to have FE features. All went on to have surgical excision. Forty (38%) contained phyllodes tumors, and 65 (62%) found no phyllodes tumor on final pathology. There were significant differences in the median size of the masses (4 cm versus 2.4 cm P phyllodes tumors and the group that did not on preoperative imaging. Further evaluation did not show any significant differences on preoperative imaging between benign and borderline/malignant phyllodes tumors. Hispanic ethnicity correlated with a higher chance of phyllodes tumor after CNB (P phyllodes tumor, surgical excision remains the standard of care; however, patients with suspicious FE neoplasms represent a treatment dilemma as many will prove to be benign. Preoperative size and the density of the mass on imaging and ethnicity were associated with phyllodes tumors on final pathology. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Gamma band plasticity in sensory cortex is a signature of the strongest memory rather than memory of the training stimulus.

    Science.gov (United States)

    Weinberger, Norman M; Miasnikov, Alexandre A; Bieszczad, Kasia M; Chen, Jemmy C

    2013-09-01

    Gamma oscillations (∼30-120Hz) are considered to be a reflection of coordinated neuronal activity, linked to processes underlying synaptic integration and plasticity. Increases in gamma power within the cerebral cortex have been found during many cognitive processes such as attention, learning, memory and problem solving in both humans and animals. However, the specificity of gamma to the detailed contents of memory remains largely unknown. We investigated the relationship between learning-induced increased gamma power in the primary auditory cortex (A1) and the strength of memory for acoustic frequency. Adult male rats (n=16) received three days (200 trials each) of pairing a tone (3.66 kHz) with stimulation of the nucleus basalis, which implanted a memory for acoustic frequency as assessed by associatively-induced disruption of ongoing behavior, viz., respiration. Post-training frequency generalization gradients (FGGs) revealed peaks at non-CS frequencies in 11/16 cases, likely reflecting normal variation in pre-training acoustic experiences. A stronger relationship was found between increased gamma power and the frequency with the strongest memory (peak of the difference between individual post- and pre-training FGGs) vs. behavioral responses to the CS training frequency. No such relationship was found for the theta/alpha band (4-15 Hz). These findings indicate that the strength of specific increased neuronal synchronization within primary sensory cortical fields can determine the specific contents of memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Muscle quality and relative adiposity are the strongest predictors of lower-extremity physical function in older women.

    Science.gov (United States)

    Straight, Chad R; Brady, Anne O; Evans, Ellen M

    2015-01-01

    The aim of this study was to examine the relative contributions of physical activity, adiposity, lean mass and muscle quality to lower-extremity physical function (LEPF) in older women. Cross-sectional analysis at a university research laboratory. Community-dwelling older women (n=96, 73.9 ± 5.6 years, BMI=26.5 ± 4.7 kg/m(2)) were assessed for body composition via dual-energy X-ray absorptiometry, leg extension power using the Nottingham power rig, muscle quality (W/kg) as the ratio of leg extension power (W) to lower-body mineral free lean mass (kg) and moderate-intensity physical activity via questionnaire. A composite measure of LEPF was calculated by summing Z-scores of the 6-min walk, 8-foot up-and-go and 30-s chair stand tests. Muscle quality and physical activity were associated with all measures of LEPF (all p0.05). Hierarchical linear regression analyses revealed that muscle quality (standardized β=0.47, pquality and relative adiposity are the strongest independent predictors of LEPF in older women. These findings suggest that maintaining muscle quality, especially relative to adiposity, may be a critical target for interventions to prevent declines in physical function in older women. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. 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.

  19. 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...... and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P

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

    Science.gov (United States)

    Fatemifar, Ghazaleh; Hoggart, Clive J.; Paternoster, Lavinia; Kemp, John P.; Prokopenko, Inga; Horikoshi, Momoko; Wright, Victoria J.; Tobias, Jon H.; Richmond, Stephen; Zhurov, Alexei I.; Toma, Arshed M.; Pouta, Anneli; Taanila, Anja; Sipila, Kirsi; Lähdesmäki, Raija; Pillas, Demetris; Geller, Frank; Feenstra, Bjarke; Melbye, Mads; Nohr, Ellen A.; Ring, Susan M.; St Pourcain, Beate; Timpson, Nicholas J.; Davey Smith, George; Jarvelin, Marjo-Riitta; Evans, David M.

    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 and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P eruption, and potentially craniofacial growth and more generally organ development. PMID:23704328

  1. Genome-wide association study identifies shared risk loci common to two malignancies in golden retrievers.

    Directory of Open Access Journals (Sweden)

    Noriko Tonomura

    2015-02-01

    Full Text Available Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6% and hemangiosarcoma (20%. We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers.

  2. Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers

    Science.gov (United States)

    Tonomura, Noriko; Elvers, Ingegerd; Thomas, Rachael; Megquier, Kate; Turner-Maier, Jason; Howald, Cedric; Sarver, Aaron L.; Swofford, Ross; Frantz, Aric M.; Ito, Daisuke; Mauceli, Evan; Arendt, Maja; Noh, Hyun Ji; Koltookian, Michele; Biagi, Tara; Fryc, Sarah; Williams, Christina; Avery, Anne C.; Kim, Jong-Hyuk; Barber, Lisa; Burgess, Kristine; Lander, Eric S.; Karlsson, Elinor K.; Azuma, Chieko

    2015-01-01

    Dogs, with their breed-determined limited genetic background, are great models of human disease including cancer. Canine B-cell lymphoma and hemangiosarcoma are both malignancies of the hematologic system that are clinically and histologically similar to human B-cell non-Hodgkin lymphoma and angiosarcoma, respectively. Golden retrievers in the US show significantly elevated lifetime risk for both B-cell lymphoma (6%) and hemangiosarcoma (20%). We conducted genome-wide association studies for hemangiosarcoma and B-cell lymphoma, identifying two shared predisposing loci. The two associated loci are located on chromosome 5, and together contribute ~20% of the risk of developing these cancers. Genome-wide p-values for the top SNP of each locus are 4.6×10-7 and 2.7×10-6, respectively. Whole genome resequencing of nine cases and controls followed by genotyping and detailed analysis identified three shared and one B-cell lymphoma specific risk haplotypes within the two loci, but no coding changes were associated with the risk haplotypes. Gene expression analysis of B-cell lymphoma tumors revealed that carrying the risk haplotypes at the first locus is associated with down-regulation of several nearby genes including the proximal gene TRPC6, a transient receptor Ca2+-channel involved in T-cell activation, among other functions. The shared risk haplotype in the second locus overlaps the vesicle transport and release gene STX8. Carrying the shared risk haplotype is associated with gene expression changes of 100 genes enriched for pathways involved in immune cell activation. Thus, the predisposing germ-line mutations in B-cell lymphoma and hemangiosarcoma appear to be regulatory, and affect pathways involved in T-cell mediated immune response in the tumor. This suggests that the interaction between the immune system and malignant cells plays a common role in the tumorigenesis of these relatively different cancers. PMID:25642983

  3. Novel genetic loci underlying human intracranial volume identified through genome-wide association.

    Science.gov (United States)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-12-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  4. Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

    Science.gov (United States)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos Santos Silva, Isabel; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Veer, Laura J Van't; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

    2013-04-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.

  5. Association of Intimate Partner Violence (IPV) and Healthcare Provider-Identified Obesity

    Science.gov (United States)

    Davies, Rhian; Lehman, Erik; Perry, Amanda; McCall-Hosenfeld, Jennifer S.

    2018-01-01

    We examined the association of physical and non-physical IPV (intimate partner violence) with obesity. Women (n=1,179) were surveyed regarding demographics, obesity, and IPV exposure using HARK (humiliate-afraid-rape-kick), an IPV screening tool. A three-level lifetime IPV exposure variable measured physical, non-physical or no IPV. Healthcare provider-identified obesity was defined if participants were told by a medical provider within the past 5 years that they were obese. Bivariate analyses examined obesity by IPV and demographics. Multivariable logistic regression assessed odds of obesity by IPV type, adjusting for age, race/ethnicity, education and marital status. Among participants, 44% reported lifetime IPV (25% physical, 19% non-physical), and 24% reported healthcare provider-identified obesity. In unadjusted analyses, obesity was more prevalent among women exposed to physical IPV (30%) and non-physical IPV (27%), compared to women without IPV (20%, p=0.002). In multivariable models, women reporting physical IPV had 1.67 times greater odds of obesity (95% confidence interval [CI] 1.20, 2.33), and women reporting non-physical IPV had 1.46 times greater odds of obesity (95% CI 1.01, 2.10) compared to women reporting never exposure. This study extends prior data by showing not only an association between physical IPV and obesity, but also an association between obesity and non-physical IPV. PMID:26495745

  6. Usability Testing of Guided Internet-based Parent Training for Challenging Behavior in Children with Fetal Alcohol Spectrum Disorder (Strongest Families FASD).

    Science.gov (United States)

    Hundert, Amos S; Huguet, Anna; Green, Courtney R; Hewitt, Amy J; Mushquash, Christopher J; Muhajarine, Nazeem; Sourander, Andre; Caughey, Heather; Lingley-Pottie, Patricia; McGrath, Patrick J; Reynolds, James N

    2016-01-01

    In order to meet the need for accessible interventions and support for families affected by fetal alcohol spectrum disorder (FASD), we have developed an Internet-based, distance intervention for caregivers of children with FASD between the ages of four and twelve, called Strongest Families™ FASD. To evaluate the usability of the Strongest Families FASD program content and website in terms of learnability, efficiency and acceptability. A remote usability testing approach was conducted in two iterative cycles of participants. Synchronous online usability testing sessions were conducted, followed by asynchronous testing. A total of 18 participants were included, comprised of both health care professionals with expertise in FASD and caregivers of children with FASD. The data collected in each cycle was examined for commonalities and results were used to inform changes to the website and content after each cycle. Participants rated the website as appealing and relatively easy and fast to use. Nevertheless, several usability problems were identified such as difficulty navigating between sections of content on the website, displaying too much content per page, and the relevance and appropriateness of the content as it related to FASD. The identification of usability problems was an important step in refining the Strongest Families FASD program before its effectiveness is evaluated in a randomized controlled trial.

  7. A graph regularized non-negative matrix factorization method for identifying microRNA-disease associations.

    Science.gov (United States)

    Xiao, Qiu; Luo, Jiawei; Liang, Cheng; Cai, Jie; Ding, Pingjian

    2017-09-01

    MicroRNAs (miRNAs) play crucial roles in post-transcriptional regulations and various cellular processes. The identification of disease-related miRNAs provides great insights into the underlying pathogenesis of diseases at a system level. However, most existing computational approaches are biased towards known miRNA-disease associations, which is inappropriate for those new diseases or miRNAs without any known association information. In this study, we propose a new method with graph regularized non-negative matrix factorization in heterogeneous omics data, called GRNMF, to discover potential associations between miRNAs and diseases, especially for new diseases and miRNAs or those diseases and miRNAs with sparse known associations. First, we integrate the disease semantic information and miRNA functional information to estimate disease similarity and miRNA similarity, respectively. Considering that there is no available interaction observed for new diseases or miRNAs, a preprocessing step is developed to construct the interaction score profiles that will assist in prediction. Next, a graph regularized non-negative matrix factorization framework is utilized to simultaneously identify potential associations for all diseases. The results indicated that our proposed method can effectively prioritize disease-associated miRNAs with higher accuracy compared with other recent approaches. Moreover, case studies also demonstrated the effectiveness of GRNMF to infer unknown miRNA-disease associations for those novel diseases and miRNAs. The code of GRNMF is freely available at https://github.com/XIAO-HN/GRNMF/. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. Genome-Wide Association Identifies SLC2A9 and NLN Gene Regions as Associated with Entropion in Domestic Sheep.

    Science.gov (United States)

    Mousel, Michelle R; Reynolds, James O; White, Stephen N

    2015-01-01

    Entropion is an inward rolling of the eyelid allowing contact between the eyelashes and cornea that may lead to blindness if not corrected. Although many mammalian species, including humans and dogs, are afflicted by congenital entropion, no specific genes or gene regions related to development of entropion have been reported in any mammalian species to date. Entropion in domestic sheep is known to have a genetic component therefore, we used domestic sheep as a model system to identify genomic regions containing genes associated with entropion. A genome-wide association was conducted with congenital entropion in 998 Columbia, Polypay, and Rambouillet sheep genotyped with 50,000 SNP markers. Prevalence of entropion was 6.01%, with all breeds represented. Logistic regression was performed in PLINK with additive allelic, recessive, dominant, and genotypic inheritance models. Two genome-wide significant (empirical Psheep genetic markers for marker-assisted selection.

  9. Identifying Sociodemographic Characteristics Associated With Burden Among Caregivers of the Urban Homebound

    Directory of Open Access Journals (Sweden)

    Ania Wajnberg MD

    2016-09-01

    Full Text Available Limited research has explored whether the burden associated with caring for homebound patients varies across racial groups or by relationship status. We examined these variations for this vulnerable population. Patients self-identified informal caregivers and caregiver burden/depression were assessed using the Zarit Caregiver Burden Scale and the Center for Epidemiologic Studies–Depression scale (CES-D. Forty-nine informal caregivers completed the interview. Mean age was 58 ( SD = 14, 78% were female, 37% Black, 35% Hispanic, and 46% had completed high school. Over 60% of caregivers had moderate or severe caregiver burden and 30% had significant depression. White caregivers had greater burden than Black and Hispanic caregivers ( p = .02. Mean caregiver burden was higher among spouse/partner caregivers, versus those who identified as children or other family or friends ( p = .004. Additional research is needed to better understand the experience of racial and ethnic minorities and spouses in providing informal care to homebound adults.

  10. PAPA: a flexible tool for identifying pleiotropic pathways using genome-wide association study summaries.

    Science.gov (United States)

    Wen, Yan; Wang, Wenyu; Guo, Xiong; Zhang, Feng

    2016-03-15

    : Pleiotropy is common in the genetic architectures of complex diseases. To the best of our knowledge, no analysis tool has been developed for identifying pleiotropic pathways using multiple genome-wide association study (GWAS) summaries by now. Here, we present PAPA, a flexible tool for pleiotropic pathway analysis utilizing GWAS summary results. The performance of PAPA was validated using publicly available GWAS summaries of body mass index and waist-hip ratio of the GIANT datasets. PAPA identified a set of pleiotropic pathways, which have been demonstrated to be involved in the development of obesity. PAPA program, document and illustrative example are available at http://sourceforge.net/projects/papav1/files/ : fzhxjtu@mail.xjtu.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Comprehensive linkage and association analyses identify haplotype, near to the TNFSF15 gene, significantly associated with spondyloarthritis.

    Directory of Open Access Journals (Sweden)

    Elena Zinovieva

    2009-06-01

    Full Text Available Spondyloarthritis (SpA is a chronic inflammatory disorder with a strong genetic predisposition dominated by the role of HLA-B27. However, the contribution of other genes to the disease susceptibility has been clearly demonstrated. We previously reported significant evidence of linkage of SpA to chromosome 9q31-34. The current study aimed to characterize this locus, named SPA2. First, we performed a fine linkage mapping of SPA2 (24 cM with 28 microsatellite markers in 149 multiplex families, which allowed us to reduce the area of investigation to an 18 cM (13 Mb locus delimited by the markers D9S279 and D9S112. Second, we constructed a linkage disequilibrium (LD map of this region with 1,536 tag single-nucleotide polymorphisms (SNPs in 136 families (263 patients. The association was assessed using a transmission disequilibrium test. One tag SNP, rs4979459, yielded a significant P-value (4.9 x 10(-5. Third, we performed an extension association study with rs4979459 and 30 surrounding SNPs in LD with it, in 287 families (668 patients, and in a sample of 139 cases and 163 controls. Strong association was observed in both familial and case/control datasets for several SNPs. In the replication study, carried with 8 SNPs in an independent sample of 232 cases and 149 controls, one SNP, rs6478105, yielded a nominal P-value<3 x 10(-2. Pooled case/control study (371 cases and 312 controls as well as combined analysis of extension and replication data showed very significant association (P<5 x 10(-4 for 6 of the 8 latter markers (rs7849556, rs10817669, rs10759734, rs6478105, rs10982396, and rs10733612. Finally, haplotype association investigations identified a strongly associated haplotype (P<8.8 x 10(-5 consisting of these 6 SNPs and located in the direct vicinity of the TNFSF15 gene. In conclusion, we have identified within the SPA2 locus a haplotype strongly associated with predisposition to SpA which is located near to TNFSF15, one of the major

  12. Proteinuria in adult Saudi patients with sickle cell disease is not associated with identifiable risk factors.

    Science.gov (United States)

    Aleem, Aamer

    2010-09-01

    Renal involvement in patients with sickle cell disease (SCD) is associated with significant morbidity and mortality. Proteinuria is common in patients with SCD and is a risk factor for future development of renal failure. We sought to identify risk factors, if any, associated with proteinuria in adult Saudi patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine collection to measure creatinine clearance and to quantify proteinuria. In addition, blood was examined for evaluation of hematological and biochemical parameters. Clinical information was gathered from review of the patients' charts. A urine protein level of more than 0.150 grams/24 hours was considered abnormal. Urine protein was correlated with various clinical and laboratory parameters. Thirty-one males and 36 females were evaluated. The mean age of the cohort was 23.8 (± 7.2) years. Twenty-seven patients (40.3%) had proteinuria of more than 0.150 grams/24 hours. The study group had a mean hemoglobin level of 8.5 (± 2.8) g/dL and mean fetal hemoglobin (HbF) level of 14.4% (± 7.3%). Majority of the patients (61) had hemoglobin SS genotype and six patients had S-ß⁰ thalassemia. None of the parameters evaluated correlated with proteinuria although there was a borderline association with older age and higher systolic blood pressure (P = 0.073 and 0.061 respectively). Hydroxyurea use for more than a year was not beneficial. In conclusion, our study suggests that proteinuria in adult Saudi patients is not associated with any clear identifiable risk factors.

  13. Identifying risk factors associated with smear positivity of pulmonary tuberculosis in Kazakhstan.

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    Sabrina Hermosilla

    Full Text Available Sputum smear-positive tuberculosis (TB patients have a high risk of transmission and are of great epidemiological and infection control significance. Little is known about the smear-positive populations in high TB burden regions, such as Kazakhstan. The objective of this study is to characterize the smear-positive population in Kazakhstan and identify associated modifiable risk factors.Data on incident TB cases' (identified between April 2012 and March 2014 socio-demographic, risk behavior, and comorbidity characteristics were collected in four regions of Kazakhstan through structured survey and medical record review. We used multivariable logistic regression to determine factors associated with smear positivity.Of the total sample, 193 (34.3% of the 562 study participants tested smear-positive. In the final adjusted multivariable logistic regression model, sex (adjusted odds ratio (aOR = 2.0, 95% CI:1.3-3.1, p < 0.01, incarceration (aOR = 3.6, 95% CI:1.2-11.1, p = 0.03, alcohol dependence (aOR = 2.6, 95% CI:1.2-5.7, p = 0.02, diabetes (aOR = 5.0, 95% CI:2.4-10.7, p < 0.01, and physician access (aOR = 2.7, 95% CI:1.3-5.5p < 0.01 were associated with smear-positivity.Incarceration, alcohol dependence, diabetes, and physician access are associated with smear positivity among incident TB cases in Kazakhstan. To stem the TB epidemic, screening, treatment and prevention policies should address these factors.

  14. Proteinuria in adult Saudi patients with sickle cell disease is not associated with identifiable risk factors

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    Aleem Aamer

    2010-01-01

    Full Text Available Renal involvement in patients with sickle cell disease (SCD is associated with signi-ficant morbidity and mortality. Proteinuria is common in patients with SCD and is a risk factor for future development of renal failure. We sought to identify risk factors, if any, associated with pro-teinuria in adult Saudi patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine collection to measure creatinine clearance and to quantify proteinuria. In addition, blood was examined for evaluation of hematological and biochemical parameters. Clinical information was gathered from review of the patients′ charts. A urine protein level of more than 0.150 grams/24 hours was consi-dered abnormal. Urine protein was correlated with various clinical and laboratory parameters. Thirty-one males and 36 females were evaluated. The mean age of the cohort was 23.8 (± 7.2 years. Twenty-seven patients (40.3% had proteinuria of more than 0.150 grams/24 hours. The study group had a mean hemoglobin level of 8.5 (± 2.8 g/dL and mean fetal hemoglobin (HbF level of 14.4% (± 7.3%. Majority of the patients (61 had hemoglobin SS genotype and six patients had S-β0 thala-ssemia. None of the parameters evaluated correlated with proteinuria although there was a border-line association with older age and higher systolic blood pressure (P = 0.073 and 0.061 respec-tively. Hydroxyurea use for more than a year was not beneficial. In conclusion, our study suggests that proteinuria in adult Saudi patients is not associated with any clear identifiable risk factors.

  15. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    International Nuclear Information System (INIS)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

    2016-01-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

  16. Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese.

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    Lai Fun Thean

    Full Text Available Genome-wide association studies (GWAS in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs that influence colorectal cancer (CRC risk.We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs, in high linkage disequilibrium (LD, r(2≥ 0.8 and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH cases and controls.Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88 but not disease prognosis (OR = 0.91, 95% CI 0.69-1.20. Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58 but not women (OR = 1.07, 95% CI: 0.88-1.29, suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ~1; p-value >0.1. Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies.The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified.

  17. Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese.

    Science.gov (United States)

    Thean, Lai Fun; Li, Hui Hua; Teo, Yik Ying; Koh, Woon-Puay; Yuan, Jian-Min; Teoh, Mei Lin; Koh, Poh Koon; Tang, Choong Leong; Cheah, Peh Yean

    2012-01-01

    Genome-wide association studies (GWAS) in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs) that influence colorectal cancer (CRC) risk. We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs), in high linkage disequilibrium (LD, r(2)≥ 0.8) and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH) cases and controls. Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR) ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88) but not disease prognosis (OR = 0.91, 95% CI 0.69-1.20). Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58) but not women (OR = 1.07, 95% CI: 0.88-1.29), suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ~1; p-value >0.1). Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies. The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified.

  18. Utility and Limitations of Using Gene Expression Data to Identify Functional Associations.

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    Sahra Uygun

    2016-12-01

    Full Text Available Gene co-expression has been widely used to hypothesize gene function through guilt-by association. However, it is not clear to what degree co-expression is informative, whether it can be applied to genes involved in different biological processes, and how the type of dataset impacts inferences about gene functions. Here our goal is to assess the utility and limitations of using co-expression as a criterion to recover functional associations between genes. By determining the percentage of gene pairs in a metabolic pathway with significant expression correlation, we found that many genes in the same pathway do not have similar transcript profiles and the choice of dataset, annotation quality, gene function, expression similarity measure, and clustering approach significantly impacts the ability to recover functional associations between genes using Arabidopsis thaliana as an example. Some datasets are more informative in capturing coordinated expression profiles and larger data sets are not always better. In addition, to recover the maximum number of known pathways and identify candidate genes with similar functions, it is important to explore rather exhaustively multiple dataset combinations, similarity measures, clustering algorithms and parameters. Finally, we validated the biological relevance of co-expression cluster memberships with an independent phenomics dataset and found that genes that consistently cluster with leucine degradation genes tend to have similar leucine levels in mutants. This study provides a framework for obtaining gene functional associations by maximizing the information that can be obtained from gene expression datasets.

  19. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    Science.gov (United States)

    Wain, Louise V; Verwoert, Germaine C; O’Reilly, Paul F; Shi, Gang; Johnson, Toby; Johnson, Andrew D; Bochud, Murielle; Rice, Kenneth M; Henneman, Peter; Smith, Albert V; Ehret, Georg B; Amin, Najaf; Larson, Martin G; Mooser, Vincent; Hadley, David; Dörr, Marcus; Bis, Joshua C; Aspelund, Thor; Esko, Tõnu; Janssens, A Cecile JW; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian’an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U; Webster, Rebecca J; Zhang, Feng; Peden, John F; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hotteng, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I; Trompet, Stella; Bragg-Gresham, Jennifer L; Alizadeh, Behrooz Z; Chambers, John C; Guo, Xiuqing; Lehtimäki, Terho; Kühnel, Brigitte; Lopez, Lorna M; Polašek, Ozren; Boban, Mladen; Nelson, Christopher P; Morrison, Alanna C; Pihur, Vasyl; Ganesh, Santhi K; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco US; Rivadeneira, Fernando; Sijbrands, Eric JG; Uitterlinden, Andre G; Hwang, Shih-Jen; Vasan, Ramachandran S; Wang, Thomas J; Bergmann, Sven; Vollenweider, Peter; Waeber, Gérard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L; Kroemer, Heyo K; Völker, Uwe; Völzke, Henry; Glazer, Nicole L; Taylor, Kent D; Harris, Tamara B; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Inês; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sõber, Siim; Lu, Xiaowen; Nolte, Ilja M; Penninx, Brenda W; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F; Melander, Olle; O’Donnell, Christopher J; Salomaa, Veikko; d’Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, M Fabiola; Facheris, Maurizio; Collins, Francis S; Bergman, Richard N; Beilby, John P; Hung, Joseph; Musk, A William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S; Navarro, Pau; Wild, Sarah H; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco JC; Willemsen, Gonneke; Parker, Alex N; Rose, Lynda M; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L; Kähönen, Mika; Viikari, Jorma; Döring, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H; ’t Hoen, Peter AC; König, Inke R; Felix, Janine F; Clarke, Robert; Hopewell, Jemma C; Ongen, Halit; Breteler, Monique; Debette, Stéphanie; DeStefano, Anita L; Fornage, Myriam; Mitchell, Gary F; Smith, Nicholas L; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J; Wichmann, H-Erich; Raitakari, Olli T; Palmas, Walter; Kooner, Jaspal S; Stolk, Ronald P; Jukema, J Wouter; Wright, Alan F; Boomsma, Dorret I; Bandinelli, Stefania; Gyllensten, Ulf B; Wilson, James F; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D; Palmer, Lyle J; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth JF; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J; Oostra, Ben A; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P; Beckmann, Jacques S; Witteman, Jacqueline CM; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B; Psaty, Bruce M; Caulfield, Mark J; Rao, Dabeeru C

    2012-01-01

    Numerous genetic loci influence systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans 1-3. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N=74,064) and follow-up studies (N=48,607), we identified at genome-wide significance (P= 2.7×10-8 to P=2.3×10-13) four novel PP loci (at 4q12 near CHIC2/PDGFRAI, 7q22.3 near PIK3CG, 8q24.12 in NOV, 11q24.3 near ADAMTS-8), two novel MAP loci (3p21.31 in MAP4, 10q25.3 near ADRB1) and one locus associated with both traits (2q24.3 near FIGN) which has recently been associated with SBP in east Asians. For three of the novel PP signals, the estimated effect for SBP was opposite to that for DBP, in contrast to the majority of common SBP- and DBP-associated variants which show concordant effects on both traits. These findings indicate novel genetic mechanisms underlying blood pressure variation, including pathways that may differentially influence SBP and DBP. PMID:21909110

  20. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    Science.gov (United States)

    Felix, Janine F.; Bradfield, Jonathan P.; Monnereau, Claire; van der Valk, Ralf J.P.; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Møller, Eskil; Mahajan, Anubha; Pitkänen, Niina; Joro, Raimo; Cavadino, Alana; Huikari, Ville; Franks, Steve; Groen-Blokhuis, Maria M.; Cousminer, Diana L.; Marsh, Julie A.; Lehtimäki, Terho; Curtin, John A.; Vioque, Jesus; Ahluwalia, Tarunveer S.; Myhre, Ronny; Price, Thomas S.; Vilor-Tejedor, Natalia; Yengo, Loïc; Grarup, Niels; Ntalla, Ioanna; Ang, Wei; Atalay, Mustafa; Bisgaard, Hans; Blakemore, Alexandra I.; Bonnefond, Amelie; Carstensen, Lisbeth; Eriksson, Johan; Flexeder, Claudia; Franke, Lude; Geller, Frank; Geserick, Mandy; Hartikainen, Anna-Liisa; Haworth, Claire M.A.; Hirschhorn, Joel N.; Hofman, Albert; Holm, Jens-Christian; Horikoshi, Momoko; Hottenga, Jouke Jan; Huang, Jinyan; Kadarmideen, Haja N.; Kähönen, Mika; Kiess, Wieland; Lakka, Hanna-Maaria; Lakka, Timo A.; Lewin, Alexandra M.; Liang, Liming; Lyytikäinen, Leo-Pekka; Ma, Baoshan; Magnus, Per; McCormack, Shana E.; McMahon, George; Mentch, Frank D.; Middeldorp, Christel M.; Murray, Clare S.; Pahkala, Katja; Pers, Tune H.; Pfäffle, Roland; Postma, Dirkje S.; Power, Christine; Simpson, Angela; Sengpiel, Verena; Tiesler, Carla M. T.; Torrent, Maties; Uitterlinden, André G.; van Meurs, Joyce B.; Vinding, Rebecca; Waage, Johannes; Wardle, Jane; Zeggini, Eleftheria; Zemel, Babette S.; Dedoussis, George V.; Pedersen, Oluf; Froguel, Philippe; Sunyer, Jordi; Plomin, Robert; Jacobsson, Bo; Hansen, Torben; Gonzalez, Juan R.; Custovic, Adnan; Raitakari, Olli T.; Pennell, Craig E.; Widén, Elisabeth; Boomsma, Dorret I.; Koppelman, Gerard H.; Sebert, Sylvain; Järvelin, Marjo-Riitta; Hyppönen, Elina; McCarthy, Mark I.; Lindi, Virpi; Harri, Niinikoski; Körner, Antje; Bønnelykke, Klaus; Heinrich, Joachim; Melbye, Mads; Rivadeneira, Fernando; Hakonarson, Hakon; Ring, Susan M.; Smith, George Davey; Sørensen, Thorkild I.A.; Timpson, Nicholas J.; Grant, Struan F.A.; Jaddoe, Vincent W.V.

    2016-01-01

    A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10−10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index. PMID:26604143

  1. Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria.

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    Watcharee Chokejindachai

    Full Text Available BACKGROUND: Studies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci. It was considered promising to undertake initial allelic association studies to prospect for virulence polymorphisms in Thailand, as the low endemicity would allow higher levels of linkage disequilibrium (LD than would exist in more highly endemic areas. METHODOLOGY/PRINCIPAL FINDINGS: Assessment of LD was first made with 11 microsatellite loci widely dispersed in the parasite genome, and 16 microsatellite loci covering a approximately 140 kb region of chromosome 2 (an arbitrarily representative non-telomeric part of the genome, in a sample of 100 P. falciparum isolates. The dispersed loci showed minimal LD (Index of Association, I(S (A = 0.013, P = 0.10, while those on chromosome 2 showed significant LD values mostly between loci <5 kb apart. A disease association study was then performed comparing parasites in 113 severe malaria cases and 245 mild malaria controls. Genotyping was performed on almost all polymorphisms in the binding domains of three erythrocyte binding antigens (eba175, eba140 and eba181, and repeat sequence polymorphisms approximately 2 kb apart in each of three reticulocyte binding homologues (Rh1, Rh2a/b, and Rh4. Differences between cases and controls were seen for (i codons 388-90 in eba175, and (ii a repeat sequence centred on Rh1 codon 667. CONCLUSIONS/SIGNIFICANCE: Allelic association studies on P. falciparum require dense genotypic markers, even in a population of only moderate endemicity that has more extensive LD than highly endemic populations. Disease-associated polymorphisms in the eba175 and Rh1 genes encode differences in the middle of previously characterised erythrocyte binding domains, marking these for further investigation.

  2. Identifying key radiogenomic associations between DCE-MRI and micro-RNA expressions for breast cancer

    Science.gov (United States)

    Samala, Ravi K.; Chan, Heang-Ping; Hadjiiski, Lubomir; Helvie, Mark A.; Kim, Renaid

    2017-03-01

    Understanding the key radiogenomic associations for breast cancer between DCE-MRI and micro-RNA expressions is the foundation for the discovery of radiomic features as biomarkers for assessing tumor progression and prognosis. We conducted a study to analyze the radiogenomic associations for breast cancer using the TCGA-TCIA data set. The core idea that tumor etiology is a function of the behavior of miRNAs is used to build the regression models. The associations based on regression are analyzed for three study outcomes: diagnosis, prognosis, and treatment. The diagnosis group consists of miRNAs associated with clinicopathologic features of breast cancer and significant aberration of expression in breast cancer patients. The prognosis group consists of miRNAs which are closely associated with tumor suppression and regulation of cell proliferation and differentiation. The treatment group consists of miRNAs that contribute significantly to the regulation of metastasis thereby having the potential to be part of therapeutic mechanisms. As a first step, important miRNA expressions were identified and their ability to classify the clinical phenotypes based on the study outcomes was evaluated using the area under the ROC curve (AUC) as a figure-of-merit. The key mapping between the selected miRNAs and radiomic features were determined using least absolute shrinkage and selection operator (LASSO) regression analysis within a two-loop leave-one-out cross-validation strategy. These key associations indicated a number of radiomic features from DCE-MRI to be potential biomarkers for the three study outcomes.

  3. 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

  4. Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.

    Directory of Open Access Journals (Sweden)

    Fergus J Couch

    Full Text Available BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer, with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8, HR = 1.14, 95% CI: 1.09-1.20. In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8, HR = 1.27, 95% CI: 1.17-1.38 and 4q32.3 (rs4691139, P = 3.4 × 10(-8, HR = 1.20, 95% CI: 1.17-1.38. The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4. These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.

  5. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

    Science.gov (United States)

    Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, François; Vincent, Daniel; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; Investigators, kConFab; Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; van Rensburg, Elizabeth J.; Hamann, Ute; Ramus, Susan J.; Ewart Toland, Amanda; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmaña, Judith; Barkardottir, Rosa B.; Arun, Banu K.; Rennert, Gad; Teo, Soo-Hwang; Ganz, Patricia A.; Campbell, Ian; van der Hout, Annemarie H.; van Deurzen, Carolien H. M.; Seynaeve, Caroline; Gómez Garcia, Encarna B.; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Gille, Johannes J. P.; Ausems, Margreet G. E. M.; Blok, Marinus J.; Ligtenberg, Marjolijn J. L.; Rookus, Matti A.; Devilee, Peter; Verhoef, Senno; van Os, Theo A. M.; Wijnen, Juul T.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Izatt, Louise; Eeles, Rosalind A.; Adlard, Julian; Eccles, Diana M.; Cook, Jackie; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley; Morrison, Patrick J.; Side, Lucy E.; Donaldson, Alan; Houghton, Catherine; Rogers, Mark T.; Dorkins, Huw; Eason, Jacqueline; Gregory, Helen; McCann, Emma; Murray, Alex; Calender, Alain; Hardouin, Agnès; Berthet, Pascaline; Delnatte, Capucine; Nogues, Catherine; Lasset, Christine; Houdayer, Claude; Leroux, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Sobol, Hagay; Coupier, Isabelle; Venat-Bouvet, Laurence; Castera, Laurent; Gauthier-Villars, Marion; Léoné, Mélanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Złowocka-Perłowska, Elżbieta; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska, Katarzyna; Huzarski, Tomasz; Spurdle, Amanda B.; Viel, Alessandra; Peissel, Bernard; Bonanni, Bernardo; Melloni, Giulia; Ottini, Laura; Papi, Laura; Varesco, Liliana; Tibiletti, Maria Grazia; Peterlongo, Paolo; Volorio, Sara; Manoukian, Siranoush; Pensotti, Valeria; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Gadzicki, Dorothea; Gehrig, Andrea; Kast, Karin; Rhiem, Kerstin; Meindl, Alfons; Niederacher, Dieter; Ditsch, Nina; Plendl, Hansjoerg; Preisler-Adams, Sabine; Engert, Stefanie; Sutter, Christian; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Weber, Bernhard H. F.; Arver, Brita; Stenmark-Askmalm, Marie; Loman, Niklas; Rosenquist, Richard; Einbeigi, Zakaria; Nathanson, Katherine L.; Rebbeck, Timothy R.; Blank, Stephanie V.; Cohn, David E.; Rodriguez, Gustavo C.; Small, Laurie; Friedlander, Michael; Bae-Jump, Victoria L.; Fink-Retter, Anneliese; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Tea, Muy-Kheng; Lindor, Noralane M.; Kaufman, Bella; Shimon Paluch, Shani; Laitman, Yael; Skytte, Anne-Bine; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Vijai, Joseph; Sarrel, Kara; Robson, Mark; Kauff, Noah; Mulligan, Anna Marie; Glendon, Gord; Ozcelik, Hilmi; Ejlertsen, Bent; Nielsen, Finn C.; Jønson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teulé, Alex; Lazaro, Conxi; Brunet, Joan; Pujana, Miquel Angel; Mai, Phuong L.; Loud, Jennifer T.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Narod, Steven A.; Herzog, Josef; Sand, Sharon R.; Tognazzo, Silvia; Agata, Simona; Vaszko, Tibor; Weaver, Joellen; Stavropoulou, Alexandra V.; Buys, Saundra S.; Romero, Atocha; de la Hoya, Miguel; Aittomäki, Kristiina; Muranen, Taru A.; Duran, Mercedes; Chung, Wendy K.; Lasa, Adriana; Dorfling, Cecilia M.; Miron, Alexander; Benitez, Javier; Senter, Leigha; Huo, Dezheng; Chan, Salina B.; Sokolenko, Anna P.; Chiquette, Jocelyne; Tihomirova, Laima; Friebel, Tara M.; Agnarsson, Bjarni A.; Lu, Karen H.; Lejbkowicz, Flavio; James, Paul A.; Hall, Per; Dunning, Alison M.; Tessier, Daniel; Cunningham, Julie; Slager, Susan L.; Wang, Chen; Hart, Steven; Stevens, Kristen; Simard, Jacques; Pastinen, Tomi; Pankratz, Vernon S.; Offit, Kenneth; Antoniou, Antonis C.

    2013-01-01

    BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10−8, HR = 1.14, 95% CI: 1.09–1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10−8, HR = 1.27, 95% CI: 1.17–1.38) and 4q32.3 (rs4691139, P = 3.4×10−8, HR = 1.20, 95% CI: 1.17–1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10−4). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%–50% compared to 81%–100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. PMID:23544013

  6. Systems Genetics Analysis to Identify the Genetic Modulation of a Glaucoma-Associated Gene.

    Science.gov (United States)

    Chintalapudi, Sumana R; Jablonski, Monica M

    2017-01-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Recently, γ-synuclein (SNCG) was shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the regulation of Sncg in RGCs, we used a systems genetics approach to identify a gene that modulates the expression of Sncg, followed by confirmatory studies in both healthy and diseased retinas. We found that chromosome 1 harbors an eQTL that modulates the expression of Sncg in the mouse retina and identified Pfdn2 as the candidate upstream modulator of Sncg expression. Downregulation of Pfdn2 in enriched RGCs causes a concomitant reduction in Sncg. In this chapter, we describe our strategy and methods for identifying and confirming a genetic modulation of a glaucoma-associated gene. A similar method can be applied to other genes expressed in other tissues.

  7. Association of recently identified type 2 diabetes gene variants with Gestational Diabetes in Asian Indian population.

    Science.gov (United States)

    Kanthimathi, Sekar; Chidambaram, Manickam; Bodhini, Dhanasekaran; Liju, Samuel; Bhavatharini, Aruyerchelvan; Uma, Ram; Anjana, Ranjit Mohan; Mohan, Viswanathan; Radha, Venkatesan

    2017-06-01

    Earlier studies have provided evidence that the gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus (T2DM) share common genetic background. A recent genome wide association study (GWAS) showed a strong association of six novel gene variants with T2DM among south Asians but not with Europeans. The aim of this study was to investigate whether these variants that confer susceptibility to T2DM in Asian Indian population also correlate with GDM in Asian Indian population. In addition to these novel variants, three T2DM associated SNPs that were previously identified by GWAS in Caucasian populations, which also showed association with T2DM in south Indian population in our previous study were also evaluated for their susceptibility to GDM in our population. The study groups comprised unrelated pregnant women with GDM (n = 518) and pregnant women with normal glucose tolerance (NGT) (n = 1220). A total of nine SNPs in or near nine loci, namely AP3S2 (rs2028299), BAZ1B (rs12056034), CDKN2A/B (rs7020996), GRB14 (rs3923113), HHEX (rs7923837), HMG20A (rs7178572), HNF4A (rs4812829), ST6GAL1 (rs16861329) and VPS26A (rs1802295) were genotyped using the MassARRAY system. Among these nine SNPs that previously showed an association with T2DM in Asian Indians, HMG20A (rs7178572) and HNF4A (rs4812829) gene variants showed a significant association with GDM. The risk alleles of rs7178572 in HMG20A and rs4812829 in HNF4A gene conferred 1.24 and 1.28 times higher risk independently and about 1.44 and 1.97 times increased susceptibility to GDM for one and two risk genotypes, respectively. We report that the HMG20A (rs7178572) and HNF4A (rs4812829) variants that have previously shown a strong association with T2DM in Asian Indians also contributes significant risk to GDM in this population. This is the first report of the association of HMG20A (rs7178572) and HNF4A (rs4812829) variants with GDM.

  8. Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke.

    Science.gov (United States)

    Barlow, Susan J

    2016-06-01

    Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n = 441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n = 42) or absence (n = 129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion-symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain.

  9. Identify Huntington's disease associated genes based on restricted Boltzmann machine with RNA-seq data.

    Science.gov (United States)

    Jiang, Xue; Zhang, Han; Duan, Feng; Quan, Xiongwen

    2017-10-11

    Predicting disease-associated genes is helpful for understanding the molecular mechanisms during the disease progression. Since the pathological mechanisms of neurodegenerative diseases are very complex, traditional statistic-based methods are not suitable for identifying key genes related to the disease development. Recent studies have shown that the computational models with deep structure can learn automatically the features of biological data, which is useful for exploring the characteristics of gene expression during the disease progression. In this paper, we propose a deep learning approach based on the restricted Boltzmann machine to analyze the RNA-seq data of Huntington's disease, namely stacked restricted Boltzmann machine (SRBM). According to the SRBM, we also design a novel framework to screen the key genes during the Huntington's disease development. In this work, we assume that the effects of regulatory factors can be captured by the hierarchical structure and narrow hidden layers of the SRBM. First, we select disease-associated factors with different time period datasets according to the differentially activated neurons in hidden layers. Then, we select disease-associated genes according to the changes of the gene energy in SRBM at different time periods. The experimental results demonstrate that SRBM can detect the important information for differential analysis of time series gene expression datasets. The identification accuracy of the disease-associated genes is improved to some extent using the novel framework. Moreover, the prediction precision of disease-associated genes for top ranking genes using SRBM is effectively improved compared with that of the state of the art methods.

  10. A Genome-Wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans

    Science.gov (United States)

    Liu, Fan; van der Lijn, Fedde; Schurmann, Claudia; Zhu, Gu; Chakravarty, M. Mallar; Hysi, Pirro G.; Wollstein, Andreas; Lao, Oscar; de Bruijne, Marleen; Ikram, M. Arfan; van der Lugt, Aad; Rivadeneira, Fernando; Uitterlinden, André G.; Hofman, Albert; Niessen, Wiro J.; Homuth, Georg; de Zubicaray, Greig; McMahon, Katie L.; Thompson, Paul M.; Daboul, Amro; Puls, Ralf; Hegenscheid, Katrin; Bevan, Liisa; Pausova, Zdenka; Medland, Sarah E.; Montgomery, Grant W.; Wright, Margaret J.; Wicking, Carol; Boehringer, Stefan; Spector, Timothy D.; Paus, Tomáš; Martin, Nicholas G.; Biffar, Reiner; Kayser, Manfred

    2012-01-01

    Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes—PRDM16, PAX3, TP63, C5orf50, and COL17A1—in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications. PMID:23028347

  11. A genome-wide association study identifies five loci influencing facial morphology in Europeans.

    Directory of Open Access Journals (Sweden)

    Fan Liu

    2012-09-01

    Full Text Available Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.

  12. Investigating predictors of eating: is resting metabolic rate really the strongest proxy of energy intake?

    Science.gov (United States)

    McNeil, Jessica; Lamothe, Gilles; Cameron, Jameason D; Riou, Marie-Ève; Cadieux, Sébastien; Lafrenière, Jacynthe; Goldfield, Gary; Willbond, Stephanie; Prud'homme, Denis; Doucet, Éric

    2017-11-01

    Background: Evidence suggests that fat-free mass and resting metabolic rate (RMR), but not fat mass, are strong predictors of energy intake (EI). However, body composition and RMR do not explain the entire variance in EI, suggesting that other factors may contribute to this variance. Objective: We aimed to investigate the associations between body mass index (in kg/m 2 ), fat mass, fat-free mass, and RMR with acute (1 meal) and daily (24-h) EI and between fasting appetite ratings and certain eating behavior traits with daily EI. We also evaluated whether RMR is a predictor of the error variance in acute and daily EI. Design: Data collected during the control condition of 7 studies conducted in Ottawa, Ontario, Canada, were included in these analyses ( n = 191 and 55 for acute and daily EI, respectively). These data include RMR (indirect calorimetry), body composition (dual-energy X-ray absorptiometry), fasting appetite ratings (visual analog scales), eating behavior traits (Three-Factor Eating Questionnaire), and EI (food buffet or menu). Results: Fat-free mass was the best predictor of acute EI ( R 2 = 0.46; P fasting prospective food consumption ratings and RMR was the best predictor of daily EI ( R 2 = 0.44; P < 0.0001). RMR was a statistically significant positive predictor of the error variance for acute ( R 2 = 0.20; P < 0.0001) and daily ( R 2 = 0.23; P < 0.0001) EI. RMR did, however, remain a statistically significant predictor of acute ( R 2 = 0.32; P < 0.0001) and daily ( R 2 = 0.30; P < 0.0001) EI after controlling for this error variance. Conclusions: Our findings suggest that combined measurements of appetite ratings and RMR could be used to estimate EI in weight-stable individuals. However, greater error variance in acute and daily EI with increasing RMR values was observed. Future studies are needed to identify whether greater fluctuations in daily EI over time occur with increasing RMR values. This trial was registered at clinicaltrials.gov as NCT

  13. Invertebrate-Based Water Quality Impairments and Associated Stressors Identified through the US Clean Water Act

    Science.gov (United States)

    Govenor, Heather; Krometis, Leigh Anne H.; Hession, W. Cully

    2017-10-01

    Macroinvertebrate community assessment is used in most US states to evaluate stream health under the Clean Water Act. While water quality assessment and impairment determinations are reported to the US Environmental Protection Agency, there is no national summary of biological assessment findings. The objective of this work was to determine the national extent of invertebrate-based impairments and to identify pollutants primarily responsible for those impairments. Evaluation of state data in the US Environmental Protection Agency's Assessment and Total Maximum Daily Load Tracking and Implementation System database revealed considerable differences in reporting approaches and terminologies including differences in if and how states report specific biological assessment findings. Only 15% of waters impaired for aquatic life could be identified as having impairments determined by biological assessments (e.g., invertebrates, fish, periphyton); approximately one-third of these were associated with macroinvertebrate bioassessment. Nearly 650 invertebrate-impaired waters were identified nationwide, and sediment was the most common pollutant in bedded (63%) and suspended (9%) forms. This finding is not unexpected, given previous work on the negative impacts of sediment on aquatic life, and highlights the need to more specifically identify the mechanisms driving sediment impairments in order to design effective remediation plans. It also reinforces the importance of efforts to derive sediment-specific biological indices and numerical sediment quality guidelines. Standardization of state reporting approaches and terminology would significantly increase the potential application of water quality assessment data, reveal national trends, and encourage sharing of best practices to facilitate the attainment of water quality goals.

  14. Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Montserrat García-Closas

    2007-02-01

    Full Text Available Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5' UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 x 10(-5. To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5' UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651 were associated with increased risk for bladder cancer: odds ratio (95% confidence interval: 2.52 (1.06-5.97, 2.74 (1.26-5.98, and 3.02 (1.36-6.63, respectively; and a polymorphism in intron 2 (rs3024994 was associated with reduced risk: 0.65 (0.46-0.91. Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5' UTR (global p = 0.02 and 0.009, respectively. These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5' UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.

  15. A genome-wide association study identifies protein quantitative trait loci (pQTLs.

    Directory of Open Access Journals (Sweden)

    David Melzer

    2008-05-01

    Full Text Available There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8x10(-57, CCL4L1 (p = 3.9x10(-21, IL18 (p = 6.8x10(-13, LPA (p = 4.4x10(-10, GGT1 (p = 1.5x10(-7, SHBG (p = 3.1x10(-7, CRP (p = 6.4x10(-6 and IL1RN (p = 7.3x10(-6 genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R, altered secretion rates of different sized proteins (LPA, variation in gene copy number (CCL4L1 and altered transcription (GGT1. We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha levels (p = 6.8x10(-40, but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis

  16. Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer

    International Nuclear Information System (INIS)

    McEvoy, Lynda M.; O’Toole, Sharon A.; Spillane, Cathy D.; Martin, Cara M.; Gallagher, Michael F.; Stordal, Britta; Blackshields, Gordon; Sheils, Orla; O’Leary, John J.

    2015-01-01

    Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance. Cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines were exposed to various combinations of hypoxia and/or chemotherapeutic drugs as part of a ‘hypoxia matrix’ designed to cover clinically relevant scenarios in terms of tumour hypoxia. Response to cisplatin was measured by the MTT assay. RNA was extracted from cells treated as part of the hypoxia matrix and interrogated on Affymetrix Human Gene ST 1.0 arrays. Differential gene expression analysis was performed for cells exposed to hypoxia and/or cisplatin. From this, four potential markers of chemoresistance were selected for evaluation in a cohort of ovarian tumour samples by RT-PCR. Hypoxia increased resistance to cisplatin in A2780 and A2780cis cells. A plethora of genes were differentially expressed in cells exposed to hypoxia and cisplatin which could be associated with chemoresistance. In ovarian tumour samples, we found trends for upregulation of ANGPTL4 in partial responders and down-regulation in non-responders compared with responders to chemotherapy; down

  17. Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls

    Science.gov (United States)

    Zhu, Zezhang; Tang, Nelson Leung-Sang; Xu, Leilei; Qin, Xiaodong; Mao, Saihu; Song, Yueming; Liu, Limin; Li, Fangcai; Liu, Peng; Yi, Long; Chang, Jiang; Jiang, Long; Ng, Bobby Kin-Wah; Shi, Benlong; Zhang, Wen; Qiao, Jun; Sun, Xu; Qiu, Xusheng; Wang, Zhou; Wang, Fei; Xie, Dingding; Chen, Ling; Chen, Zhonghui; Jin, Mengran; Han, Xiao; Hu, Zongshan; Zhang, Zhen; Liu, Zhen; Zhu, Feng; Qian, Bang-ping; Yu, Yang; Wang, Bing; Lee, K. M.; Lee, Wayne Y.W.; Lam, T. P.; Qiu, Yong; Cheng, Jack Chun-Yiu

    2015-01-01

    Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS. PMID:26394188

  18. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  19. Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

    Science.gov (United States)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

    2013-04-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  20. Applying an observational lens to identify parental behaviours associated with children's homework motivation.

    Science.gov (United States)

    Pino-Pasternak, Deborah

    2014-09-01

    Extant research has traditionally associated children's achievement motivation with socio-emotional parental behaviours such as demonstrations of affect, responsiveness, and the degree of parental control. This study explored the extent to which parental socio-emotional and instructional behaviours (including the contingency of instructional scaffolding) both related to children's mastery and performance tendencies towards homework-like activities. The study involved nine underachieving primary-aged children and their parents, with four children showing predominantly mastery-oriented behaviours in the homework context and five showing predominantly performance-oriented behaviours. An in-depth observational analysis of video-recorded parent-child interactions during four homework-like sessions was carried out for each case. Socio-emotional and instructional parental behaviours were coded and subjected to nonparametric quantitative analyses. Subsequently, thick descriptions of parent-child interactions were used to identify critical aspects of parental assistance. Moderate cognitive demand was associated with mastery orientation, while negative affect was related to performance orientation. As revealed quantitatively and qualitatively, socio-emotional and instructional parental behaviours were also associated with each other, forming distinct profiles of parental behaviours related to children's homework motivation. The findings support the idea that instructional parental behaviours are as important as socio-emotional ones in the analysis of children's homework motivation. The value of observational methods in investigating the target variables is discussed. © 2014 The British Psychological Society.

  1. Expression profiling feline peripheral blood monocytes identifies a transcriptional signature associated with type two diabetes mellitus.

    Science.gov (United States)

    O'Leary, Caroline A; Sedhom, Mamdouh; Reeve-Johnson, Mia; Mallyon, John; Irvine, Katharine M

    2017-04-01

    Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes (T2D) in humans, especially with respect to the role of obesity-induced insulin resistance, glucose toxicity, decreased number of pancreatic β-cells and pancreatic amyloid deposition. Cats have thus been proposed as a valuable translational model of T2D. In humans, inflammation associated with adipose tissue is believed to be central to T2D development, and peripheral blood monocytes (PBM) are important in the inflammatory cascade which leads to insulin resistance and β-cell failure. PBM may thus provide a useful window to study the pathogenesis of diabetes mellitus in cats, however feline monocytes are poorly characterised. In this study, we used the Affymetrix Feline 1.0ST array to profile peripheral blood monocytes from 3 domestic cats with T2D and 3 cats with normal glucose tolerance. Feline monocytes were enriched for genes expressed in human monocytes, and, despite heterogeneous gene expression, we identified a T2D-associated expression signature associated with cell cycle perturbations, DNA repair and the unfolded protein response, oxidative phosphorylation and inflammatory responses. Our data provide novel insights into the feline monocyte transcriptome, and support the hypothesis that inflammatory monocytes contribute to T2D pathogenesis in cats as well as in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Identifying Associations Between Brain Imaging Phenotypes and Genetic Factors via A Novel Structured SCCA Approach.

    Science.gov (United States)

    Du, Lei; Zhang, Tuo; Liu, Kefei; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Han, Junwei; Guo, Lei; Shen, Li

    2017-06-01

    Brain imaging genetics attracts more and more attention since it can reveal associations between genetic factors and the structures or functions of human brain. Sparse canonical correlation analysis (SCCA) is a powerful bi-multivariate association identification technique in imaging genetics. There have been many SCCA methods which could capture different types of structured imaging genetic relationships. These methods either use the group lasso to recover the group structure, or employ the graph/network guided fused lasso to find out the network structure. However, the group lasso methods have limitation in generalization because of the incomplete or unavailable prior knowledge in real world. The graph/network guided methods are sensitive to the sign of the sample correlation which may be incorrectly estimated. We introduce a new SCCA model using a novel graph guided pairwise group lasso penalty, and propose an efficient optimization algorithm. The proposed method has a strong upper bound for the grouping effect for both positively and negatively correlated variables. We show that our method performs better than or equally to two state-of-the-art SCCA methods on both synthetic and real neuroimaging genetics data. In particular, our method identifies stronger canonical correlations and captures better canonical loading profiles, showing its promise for revealing biologically meaningful imaging genetic associations.

  3. Identifying selectively important amino acid positions associated with alternative habitat environments in fish mitochondrial genomes.

    Science.gov (United States)

    Xia, Jun Hong; Li, Hong Lian; Zhang, Yong; Meng, Zi Ning; Lin, Hao Ran

    2017-04-19

    Fish species inhabitating seawater (SW) or freshwater (FW) habitats have to develop genetic adaptations to alternative environment factors, especially salinity. Functional consequences of the protein variations associated with habitat environments in fish mitochondrial genomes have not yet received much attention. We analyzed 829 complete fish mitochondrial genomes and compared the amino acid differences of 13 mitochondrial protein families between FW and SW fish groups. We identified 47 specificity determining sites (SDS) that associated with FW or SW environments from 12 mitochondrial protein families. Thirty-two (68%) of the SDS sites are hydrophobic, 13 (28%) are neutral, and the remaining sites are acidic or basic. Seven of those SDS from ND1, ND2 and ND5 were scored as probably damaging to the protein structures. Furthermore, phylogenetic tree based Bayes Empirical Bayes analysis also detected 63 positive sites associated with alternative habitat environments across ten mtDNA proteins. These signatures could be important for studying mitochondrial genetic variation relevant to fish physiology and ecology.

  4. New genes associated with rheumatoid arthritis identified by gene expression profiling.

    Science.gov (United States)

    Wang, H; Guo, J; Jiang, J; Wu, W; Chang, X; Zhou, H; Li, Z; Zhao, J

    2017-06-01

    In this study, we aimed to find new genes associated with rheumatoid arthritis (RA) so that more comprehensive genes would be used for monitoring and/or diagnosing patients. Illumina digital gene expression profiling was applied in two sample types - peripheral blood mononuclear cells (PBMCs) and synovial cells to compare the gene expression pattern between 17 patients with RA and three control groups (six osteoarthritis patients, three ankylosing spondylitis patients and 17 healthy controls). Bioinformatics was performed on pathway analysis and protein-protein interaction networks. Four novel genes from PBMCs - DHRS3, TTC38, SAP30BP and LPIN2 - were found to be associated with RA and further confirmed through quantitative real-time polymerase chain reaction. Five new differentially expressed genes (EPYC, LIFR, GLDN, TADA3 and ZNRF3) found in synovial cells were not confirmed. Pathway analyses revealed 10 significantly enriched pathways, and a protein-protein interaction network analysis showed that four novel PBMC-derived genes were connected to previously reported genes by four intermediate genes. Therefore, we proposed that four newly identified PBMC-derived genes could be integrated with previously reported RA-associated genes to monitor and/or diagnose RA. © 2017 John Wiley & Sons Ltd.

  5. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    Science.gov (United States)

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

  6. A genome-wide association study identifies novel single nucleotide polymorphisms associated with dermal shank pigmentation in chickens.

    Science.gov (United States)

    Li, Guangqi; Li, Dongfeng; Yang, Ning; Qu, Lujiang; Hou, Zhuocheng; Zheng, Jiangxia; Xu, Guiyun; Chen, Sirui

    2014-12-01

    Shank color of domestic chickens varies from black to blue, green, yellow, or white, which is controlled by the combination of melanin and xanthophylls in dermis and epidermis. Dermal shank pigmentation of chickens is determined by sex-linked inhibitor of dermal melanin (Id), which is located on the distal end of the long arm of Z chromosome, through controlling dermal melanin pigmentation. Although previous studies have focused on the identification of Id and the linear relationship with barring and recessive white skin, no causal mutations have yet been identified in relation to the mutant dermal pigment inhibiting allele at the Id locus. In this study, we first used the 600K Affymetrix Axiom HD genotyping array, which includes ~580,961 SNP of which 26,642 SNP were on the Z chromosome to perform a genome-wide association study on pure lines of 19 Tibetan hens with dermal pigmentation shank and 21 Tibetan hens with yellow shank to refine the Id location. Association analysis was conducted by the PLINK software using the standard chi-squared test, and then Bonferroni correction was used to adjust multiple testing. The genome-wide study revealed that 3 SNP located at 78.5 to 79.2 Mb on the Z chromosome in the current assembly of chicken genome (galGal4) were significantly associated with dermal shank pigmentation of chickens, but none of them were located in known genes. The interval we refined was partly converged with previous results, suggesting that the Id gene is in or near our refined genome region. However, the genomic context of this region was complex. There were only 15 SNP markers developed by the genotyping array within the interval region, in which only 1 SNP marker passed quality control. Additionally, there were about 5.8-Mb gaps on both sides of the refined interval. The follow-up replication studies may be needed to further confirm the functional significance for these newly identified SNP. ©2014 Poultry Science Association Inc.

  7. Alternative splicing enriched cDNA libraries identify breast cancer-associated transcripts

    Science.gov (United States)

    2010-01-01

    Background Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human diseases. Cancer-associated transcripts are potential molecular markers and may contribute to the development of more accurate diagnostic and prognostic methods and also serve as therapeutic targets. Alternative splicing-enriched cDNA libraries have been used to explore the variability generated by alternative splicing. In this study, by combining the use of trapping heteroduplexes and RNA amplification, we developed a powerful approach that enables transcriptome-wide exploration of the AS repertoire for identifying AS variants associated with breast tumor cells modulated by ERBB2 (HER-2/neu) oncogene expression. Results The human breast cell line (C5.2) and a pool of 5 ERBB2 over-expressing breast tumor samples were used independently for the construction of two AS-enriched libraries. In total, 2,048 partial cDNA sequences were obtained, revealing 214 alternative splicing sequence-enriched tags (ASSETs). A subset with 79 multiple exon ASSETs was compared to public databases and reported 138 different AS events. A high success rate of RT-PCR validation (94.5%) was obtained, and 2 novel AS events were identified. The influence of ERBB2-mediated expression on AS regulation was evaluated by capillary electrophoresis and probe-ligation approaches in two mammary cell lines (Hb4a and C5.2) expressing different levels of ERBB2. The relative expression balance between AS variants from 3 genes was differentially modulated by ERBB2 in this model system. Conclusions In this study, we presented a method for exploring AS from any RNA source in a transcriptome-wide format, which can be directly easily adapted to next generation sequencers. We identified AS transcripts

  8. Functional genomics complements quantitative genetics in identifying disease-gene associations.

    Directory of Open Access Journals (Sweden)

    Yuanfang Guan

    2010-11-01

    Full Text Available An ultimate goal of genetic research is to understand the connection between genotype and phenotype in order to improve the diagnosis and treatment of diseases. The quantitative genetics field has developed a suite of statistical methods to associate genetic loci with diseases and phenotypes, including quantitative trait loci (QTL linkage mapping and genome-wide association studies (GWAS. However, each of these approaches have technical and biological shortcomings. For example, the amount of heritable variation explained by GWAS is often surprisingly small and the resolution of many QTL linkage mapping studies is poor. The predictive power and interpretation of QTL and GWAS results are consequently limited. In this study, we propose a complementary approach to quantitative genetics by interrogating the vast amount of high-throughput genomic data in model organisms to functionally associate genes with phenotypes and diseases. Our algorithm combines the genome-wide functional relationship network for the laboratory mouse and a state-of-the-art machine learning method. We demonstrate the superior accuracy of this algorithm through predicting genes associated with each of 1157 diverse phenotype ontology terms. Comparison between our prediction results and a meta-analysis of quantitative genetic studies reveals both overlapping candidates and distinct, accurate predictions uniquely identified by our approach. Focusing on bone mineral density (BMD, a phenotype related to osteoporotic fracture, we experimentally validated two of our novel predictions (not observed in any previous GWAS/QTL studies and found significant bone density defects for both Timp2 and Abcg8 deficient mice. Our results suggest that the integration of functional genomics data into networks, which itself is informative of protein function and interactions, can successfully be utilized as a complementary approach to quantitative genetics to predict disease risks. All supplementary

  9. Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

    Science.gov (United States)

    McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

    2013-04-01

    Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate ( p = 4.4 × 10 -5 , q = 0.013), tryptophan ( p = 7.0 × 10 -4 , q = 0.035) and 2-hydroxyglutarate ( p = 1.1 × 10 -4 , q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate ( p = 3.8 × 10 -7 ). Associations specific to repeated (5 day) MA exposure included phosphocholine ( p = 4.0 × 10 -4 , q = 0.087) and ergothioneine ( p = 3.0 × 10 -4 , q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects.

  10. Extended tracts of homozygosity identify novel candidate genes associated with late onset Alzheimer’s Disease

    Science.gov (United States)

    Nalls, M. A.; Guerreiro, R. J.; Simon-Sanchez, J.; Bras, J. T.; Traynor, B. J.; Gibbs, J. R.; Launer, L.; Hardy, J.; Singleton, A. B.

    2010-01-01

    Large tracts of extended homozygosity are more prevalent in outbred populations than previously thought. With the advent of high-density genotyping platforms, regions of extended homozygosity can be accurately located allowing for the identification of rare recessive risk variants contributing to disease. We compared measures of extended homozygosity (greater than 1 megabase in length) in a population of 837 late onset Alzheimer’s disease (LOAD) cases and 550 controls. In our analyses, we identify one homozygous region on chromosome 8 that is significantly associated with LOAD after adjusting for multiple testing. This region contains seven genes from which the most biologically plausible candidates are STAR, EIF4EBP1 and ADRB3. We also compared the total numbers of homozygous runs and the total length of these runs between cases and controls, showing a suggestive difference in these measures (p-values 0.052-0.062). This research suggests a recessive component to the etiology of LOAD. PMID:19271249

  11. Genome-wide association study identifies three novel loci for type 2 diabetes

    DEFF Research Database (Denmark)

    Hara, Kazuo; Fujita, Hayato; Johnson, Todd A

    2014-01-01

    genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases...... (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.......Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly...

  12. Time distortion associated with smartphone addiction: Identifying smartphone addiction via a mobile application (App).

    Science.gov (United States)

    Lin, Yu-Hsuan; Lin, Yu-Cheng; Lee, Yang-Han; Lin, Po-Hsien; Lin, Sheng-Hsuan; Chang, Li-Ren; Tseng, Hsien-Wei; Yen, Liang-Yu; Yang, Cheryl C H; Kuo, Terry B J

    2015-06-01

    Global smartphone penetration has brought about unprecedented addictive behaviors. We report a proposed diagnostic criteria and the designing of a mobile application (App) to identify smartphone addiction. We used a novel empirical mode decomposition (EMD) to delineate the trend in smartphone use over one month. The daily use count and the trend of this frequency are associated with smartphone addiction. We quantify excessive use by daily use duration and frequency, as well as the relationship between the tolerance symptoms and the trend for the median duration of a use epoch. The psychiatrists' assisted self-reporting use time is significant lower than and the recorded total smartphone use time via the App and the degree of underestimation was positively correlated with actual smartphone use. Our study suggests the identification of smartphone addiction by diagnostic interview and via the App-generated parameters with EMD analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.

    Science.gov (United States)

    Carey, Maureen A; Papin, Jason A; Guler, Jennifer L

    2017-07-19

    Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P. falciparum parasite to expand our understanding of metabolic changes that support resistance. We identified 11 metabolic tasks to evaluate iPfal17 performance. Flux balance analysis and simulation of gene knockouts and enzyme inhibition predict candidate drug targets unique to resistant parasites. Moreover, integration of clinical parasite transcriptomes into the iPfal17 reconstruction reveals patterns associated with antimalarial resistance. These results predict that artemisinin sensitive and resistant parasites differentially utilize scavenging and biosynthetic pathways for multiple essential metabolites, including folate and polyamines. Our findings are consistent with experimental literature, while generating novel hypotheses about artemisinin resistance and parasite biology. We detect evidence that resistant parasites maintain greater metabolic flexibility, perhaps representing an incomplete transition to the metabolic state most appropriate for nutrient-rich blood. Using this systems biology approach, we identify metabolic shifts that arise with or in support of the resistant phenotype. This perspective allows us to more productively analyze and interpret clinical expression data for the identification of candidate drug targets for the treatment of resistant parasites.

  14. Patterns of Seismicity Associated with USGS Identified Areas of Potentially Induced Seismicity.

    Science.gov (United States)

    Barnes, Caitlin; Halihan, Todd

    2018-03-13

    A systematic review across U.S. Geological Survey (USGS) identified potentially induced seismic locations was conducted to discover seismic distance patterns and trends over time away from injection disposal wells. Previous research indicates a 10 km (6 miles) average where the majority of induced seismicity is expected to occur within individual locations, with some areas reporting a larger radius of 35 km (22 miles) to over 70 km (43 miles). This research analyzed earthquake occurrences within nine USGS locations where specified wells were identified as contributors to induced seismicity to determine distance patterns from disposal wells or outward seismic migration over time using established principles of hydrogeology. Results indicate a radius of 31.6 km (20 miles) where 90% of felt earthquakes occur among locations, with the closest proximal felt seismic events, on average, occurring 3 km (1.9 miles) away from injection disposal wells. The results of this research found distance trends across multiple locations of potentially induced seismicity. © 2018, National Ground Water Association.

  15. Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis

    Science.gov (United States)

    Kind, Tobias; Cho, Eunho; Park, Taeeun D.; Deng, Nan; Liu, Zhenqiu; Lee, Tack; Fiehn, Oliver; Kim, Jayoung

    2016-01-01

    This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms. PMID:27976711

  16. The use of functional chemical-protein associations to identify multi-pathway renoprotectants.

    Directory of Open Access Journals (Sweden)

    Jia Xu

    Full Text Available Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1, which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted p = 1.5×10-5. At the same concentration (10 µM, both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.

  17. Functional profiling of microtumors to identify cancer associated fibroblast-derived drug targets.

    Science.gov (United States)

    Horman, Shane R; To, Jeremy; Lamb, John; Zoll, Jocelyn H; Leonetti, Nicole; Tu, Buu; Moran, Rita; Newlin, Robbin; Walker, John R; Orth, Anthony P

    2017-11-21

    Recent advances in chemotherapeutics highlight the importance of molecularly-targeted perturbagens. Although these therapies typically address dysregulated cancer cell proteins, there are increasing therapeutic modalities that take into consideration cancer cell-extrinsic factors. Targeting components of tumor stroma such as vascular or immune cells has been shown to represent an efficacious approach in cancer treatment. Cancer-associated fibroblasts (CAFs) exemplify an important stromal component that can be exploited in targeted therapeutics, though their employment in drug discovery campaigns has been relatively minimal due to technical logistics in assaying for CAF-tumor interactions. Here we report a 3-dimensional multi-culture tumor:CAF spheroid phenotypic screening platform that can be applied to high-content drug discovery initiatives. Using a functional genomics approach we systematically profiled 1,024 candidate genes for CAF-intrinsic anti-spheroid activity; identifying several CAF genes important for development and maintenance of tumor:CAF co-culture spheroids. Along with previously reported genes such as WNT, we identify CAF-derived targets such as ARAF and COL3A1 upon which the tumor compartment depends for spheroid development. Specifically, we highlight the G-protein-coupled receptor OGR1 as a unique CAF-specific protein that may represent an attractive drug target for treating colorectal cancer. In vivo , murine colon tumor implants in OGR1 knockout mice displayed delayed tumor growth compared to tumors implanted in wild type littermate controls. These findings demonstrate a robust microphysiological screening approach for identifying new CAF targets that may be applied to drug discovery efforts.

  18. Genome-wide association analysis identifies potential regulatory genes for eumelanin pigmentation in chicken plumage.

    Science.gov (United States)

    Yang, L; Du, X; Wei, S; Gu, L; Li, N; Gong, Y; Li, S

    2017-10-01

    Plumage color in chicken is determined by the proportion of eumelanin and pheomelanin pigmentation. As the main ingredient in plumage melanin, eumelanin plays a key role in the dark black, brown and grey coloration. However, very few studies have been performed to identify the related genes and mutations on a genome-wide scale. Herein, a resource family consisting of one backcross population and two F2 cross populations between a black roster and Yukou Brown I parent stockbreed was constructed for identification of genes related to eumelanin pigmentation. Chickens with eumelanin in their plumage were classified as the case group, and the rest were considered the control group. A genome-wide association study of this phenotype and genotypes using Affymetrix 600K HD SNP arrays in this F2 family revealed 13 significantly associated SNPs and in 10 separate genes on chromosomes 1, 2, 3 and 5. Based on previous studies in model species, we inferred that genes, including NUAK family kinase 1 (NUAK1) and sonic hedgehog (SHH), may play roles in the development of neural crest cells or melanoblasts during the embryonic period, which may also affect the eumelanin pigmentation. Our results facilitate the understanding of the genetic basis of eumelanin pigmentation in chicken plumage. © 2017 Stichting International Foundation for Animal Genetics.

  19. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

    NARCIS (Netherlands)

    Horikoshi, M.; Yaghootkar, H.; Mook-Kanamori, D.O.; Sovio, U.; Taal, H.R.; Hennig, B.J.; Bradfield, J.P.; St Pourcain, B.; Evans, D.M.; Charoen, P.; Kaakinen, M.; Cousminer, D.L.; Lehtimäki, T.; Kreiner-Møller, E.; Warrington, N.M.; Bustamante, M.; Feenstra, B.; Berry, D.J.; Thiering, E.; Pfab, T.; Barton, S.J.; Shields, B.M.; Kerkhof, M.; Leeuwen, E. M.; Fulford, A.J.; Kutalik, Z.; Zhao, J.H.; van den Hoed, M.; Mahajan, A.; Lindi, V.; Goh, L.K.; Hottenga, J.J.; Wu, Y.; Raitakari, O.T.; Harder, M.N.; Meirhaeghe, A.; Ntalla, I.; Salem, R.M.; Jameson, K.A.; Zhou, K.; Monies, D.M.; Lagou, V.; Kirin, M.; Heikkinen, J.; Adair, L.S.; Alkuraya, F.S.; Al-Odaib, A.; Amouyel, P.; Andersson, E.A.; Bennett, A.J.; Blakemore, A.I.F.; Buxton, J.L.; Dallongeville, J.; Das, S.; de Geus, E.J.C.; Estivill, X.; Flexeder, C.; Froguel, P.; Geller, F.; Godfrey, K.M.; Gottrand, F.; Groves, C.J.; Hansen, T.; Hirschhorn, J.N.; Hofman, A.; Hollegaard, M.V.; Hougaard, D. M.; Hyppönen, E.; Inskip, H.M.; Isaacs, A.; Jørgensen, T.; Kanaka-Gantenbein, C.; Kemp, J.P.; Kiess, W.; Kilpeläinen, T.O.; Klopp, N.; Knight, B.A.; Kuzawa, C.W.; McMahon, G.; Newnham, J.P.; Niinikoski, H.; Oostra, B.A.; Pedersen, L.; Postma, D.S.; Ring, S.M.; Rivadeneira, F.; Robertson, N.R.; Sebert, S.; Simell, O.; Slowinski, T.; Tiesler, C.M.T.; Tönjes, A.; Vaag, A.A.; Viikari, J.S.; Vink, J.M.; Vissing, N.H.; Wareham, N.J.; Willemsen, G.; Witte, D.R.; Zhang, H.; Zhao, J.; Wilson, J.F.; Stumvoll, M.; Prentice, A.M.; Meyer, B.F.; Pearson, E.R.; Boreham, C.A.; Cooper, C.; Gillman, M.W.; Dedoussis, G.V.; Moreno, L.A.; Pedersen, O.; Saarinen, M.; Mohlke, K.L.; Boomsma, D.I.; Saw, S.M.; Lakka, T.A.; Körner, A.; Loos, R.J.; Ong, K.K.; Vollenweider, P.; van Duijn, C.M.; Koppelman, G.H.; Hattersley, A.T.; Holloway, J.W.; Hocher, B.; Heinrich, J.; Power, C.; Melbye, M.; Guxens, M.; Pennell, C.E.; Bønnelykke, K.; Bisgaard, H.; Eriksson, J.G.; Widén, E.; Hakonarson, H.; Uitterlinden, A.G.; Pouta, A.; Lawlor, D.A.; Smith, G.D.; Frayling, T.M.; McCarthy, M.I.; Grant, S.F.; Jaddoe, V.W.; Järvelin, M.R.; Timpson, N.J.; Prokopenko, I.; Freathy, R.M.

    2013-01-01

    Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2

  20. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

    NARCIS (Netherlands)

    Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O.; Sovio, Ulla; Taal, H. Rob; Hennig, Branwen J.; Bradfield, Jonathan P.; St Pourcain, Beate; Evans, David M.; Charoen, Pimphen; Kaakinen, Marika; Cousminer, Diana L.; Lehtimaki, Terho; Kreiner-Moller, Eskil; Warrington, Nicole M.; Bustamante, Mariona; Feenstra, Bjarke; Berry, Diane J.; Thiering, Elisabeth; Pfab, Thiemo; Barton, Sheila J.; Shields, Beverley M.; Kerkhof, Marjan; van Leeuwen, Elisa; Fulford, Anthony J.; Kutalik, Zoltan; Zhao, Jing Hua; den Hoed, Marcel; Mahajan, Anubha; Lindi, Virpi; Goh, Liang-Kee; Hottenga, Jouke-Jan; Wu, Ying; Raitakari, Olli T.; Harder, Marie N.; Meirhaeghe, Aline; Ntalla, Ioanna; Salem, Rany M.; Jameson, Karen A.; Zhou, Kaixin; Monies, Dorota M.; Lagou, Vasiliki; Kirin, Mirna; Heikkinen, Jani; Adair, Linda S.; Alkuraya, Fowzan S.; Al-Odaib, Ali; Amouyel, Philippe; Andersson, Ehm Astrid; Bennett, Amanda J.; Blakemore, Alexandra I. F.; Buxton, Jessica L.; Dallongeville, Jean; Das, Shikta; de Geus, Eco J. C.; Estivill, Xavier; Flexeder, Claudia; Froguel, Philippe; Geller, Frank; Godfrey, Keith M.; Gottrand, Frederic; Groves, Christopher J.; Hansen, Torben; Hirschhorn, Joel N.; Hofman, Albert; Hollegaard, Mads V.; Hougaard, David M.; Hyppoenen, Elina; Inskip, Hazel M.; Isaacs, Aaron; Jorgensen, Torben; Kanaka-Gantenbein, Christina; Kemp, John P.; Kiess, Wieland; Kilpelainen, Tuomas O.; Klopp, Norman; Knight, Bridget A.; Kuzawa, Christopher W.; McMahon, George; Newnham, John P.; Niinikoski, Harri; Oostra, Ben A.; Pedersen, Louise; Postma, Dirkje S.; Ring, Susan M.; Rivadeneira, Fernando; Robertson, Neil R.; Sebert, Sylvain; Simell, Olli; Slowinski, Torsten; Tiesler, Carla M. T.; Toenjes, Anke; Vaag, Allan; Viikari, Jorma S.; Vink, Jacqueline M.; Vissing, Nadja Hawwa; Wareham, Nicholas J.; Willemsen, Gonneke; Witte, Daniel R.; Zhang, Haitao; Zhao, Jianhua; Wilson, James F.; Stumvoll, Michael; Prentice, Andrew M.; Meyer, Brian F.; Pearson, Ewan R.; Boreham, Colin A. G.; Cooper, Cyrus; Gillman, Matthew W.; Dedoussis, George V.; Moreno, Luis A.; Pedersen, Oluf; Saarinen, Maiju; Mohlke, Karen L.; Boomsma, Dorret I.; Saw, Seang-Mei; Lakka, Timo A.; Koerner, Antje; Loos, Ruth J. F.; Ong, Ken K.; Vollenweider, Peter; van Duijn, Cornelia M.; Koppelman, Gerard H.; Hattersley, Andrew T.; Holloway, John W.; Hocher, Berthold; Heinrich, Joachim; Power, Chris; Melbye, Mads; Guxens, Monica; Pennell, Craig E.; Bonnelykke, Klaus; Bisgaard, Hans; Eriksson, Johan G.; Widen, Elisabeth; Hakonarson, Hakon; Uitterlinden, Andre G.; Pouta, Anneli; Lawlor, Debbie A.; Smith, George Davey; Frayling, Timothy M.; McCarthy, Mark I.; Grant, Struan F. A.; Jaddoe, Vincent W. V.; Jarvelin, Marjo-Riitta; Timpson, Nicholas J.; Prokopenko, Inga; Freathy, Rachel M.

    Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type

  1. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Klaus Stark

    2010-10-01

    Full Text Available Dilated cardiomyopathy (DCM is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39% and idiopathic DCM (p = 1.06 × 10⁻⁶, OR  = 0.67 [95% CI 0.57-0.79] for the minor allele T. Three more SNPs showed p < 2.21 × 10⁻⁵. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n =564, n = 981 controls, p = 2.07 × 10⁻³, OR = 0.79 [95% CI 0.67-0.92], France 1 (n = 433 cases, n = 395 controls, p =3.73 × 10⁻³, OR  = 0.74 [95% CI 0.60-0.91], and France 2 (n = 249 cases, n = 380 controls, p = 2.26 × 10⁻⁴, OR  = 0.63 [95% CI 0.50-0.81]. The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28 × 10⁻¹³, OR= 0.72 [95% CI 0.65-0.78]. None of the other three SNPs showed significant results in the replication stage.This finding of the HSPB7 gene from a genetic search for idiopathic DCM using

  2. Genetic Association Study Identifies HSPB7 as a Risk Gene for Idiopathic Dilated Cardiomyopathy

    Science.gov (United States)

    Stark, Klaus; Esslinger, Ulrike B.; Reinhard, Wibke; Petrov, George; Winkler, Thomas; Komajda, Michel; Isnard, Richard; Charron, Philippe; Villard, Eric; Cambien, François; Tiret, Laurence; Aumont, Marie-Claude; Dubourg, Olivier; Trochu, Jean-Noël; Fauchier, Laurent; DeGroote, Pascal; Richter, Anette; Maisch, Bernhard; Wichter, Thomas; Zollbrecht, Christa; Grassl, Martina; Schunkert, Heribert; Linsel-Nitschke, Patrick; Erdmann, Jeanette; Baumert, Jens; Illig, Thomas; Klopp, Norman; Wichmann, H.-Erich; Meisinger, Christa; Koenig, Wolfgang; Lichtner, Peter; Meitinger, Thomas; Schillert, Arne; König, Inke R.; Hetzer, Roland; Heid, Iris M.; Regitz-Zagrosek, Vera; Hengstenberg, Christian

    2010-01-01

    Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06×10−6, OR = 0.67 [95% CI 0.57–0.79] for the minor allele T). Three more SNPs showed p < 2.21×10−5. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n = 564, n = 981 controls, p = 2.07×10−3, OR = 0.79 [95% CI 0.67–0.92]), France 1 (n = 433 cases, n = 395 controls, p = 3.73×10−3, OR = 0.74 [95% CI 0.60–0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26×10−4, OR = 0.63 [95% CI 0.50–0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28×10−13, OR = 0.72 [95% CI 0.65–0.78]). None of the other three SNPs showed significant results in the replication stage. This finding of the HSPB7 gene from a

  3. Identifying Dietary Patterns Associated with Mild Cognitive Impairment in Older Korean Adults Using Reduced Rank Regression

    Directory of Open Access Journals (Sweden)

    Dayeon Shin

    2018-01-01

    Full Text Available Diet plays a crucial role in cognitive function. Few studies have examined the relationship between dietary patterns and cognitive functions of older adults in the Korean population. This study aimed to identify the effect of dietary patterns on the risk of mild cognitive impairment. A total of 239 participants, including 88 men and 151 women, aged 65 years and older were selected from health centers in the district of Seoul, Gyeonggi province, and Incheon, in Korea. Dietary patterns were determined using Reduced Rank Regression (RRR methods with responses regarding vitamin B6, vitamin C, and iron intakes, based on both a one-day 24-h recall and a food frequency questionnaire. Cognitive function was assessed using the Korean-Mini Mental State Examination (K-MMSE. Multivariable logistic regression models were used to estimate the association between dietary pattern score and the risk of mild cognitive impairment. A total of 20 (8% out of the 239 participants had mild cognitive impairment. Three dietary patterns were identified: seafood and vegetables, high meat, and bread, ham, and alcohol. Among the three dietary patterns, the older adult population who adhered to the seafood and vegetables pattern, characterized by high intake of seafood, vegetables, fruits, bread, snacks, soy products, beans, chicken, pork, ham, egg, and milk had a decreased risk of mild cognitive impairment compared to those who did not (adjusted odds ratios 0.06, 95% confidence interval 0.01–0.72 after controlling for gender, supplementation, education, history of dementia, physical activity, body mass index (BMI, and duration of sleep. The other two dietary patterns were not significantly associated with the risk of mild cognitive impairment. In conclusion, high consumption of fruits, vegetables, seafood, and protein foods was significantly associated with reduced mild cognitive impairment in older Korean adults. These results can contribute to the establishment of

  4. Identifying Dietary Patterns Associated with Mild Cognitive Impairment in Older Korean Adults Using Reduced Rank Regression.

    Science.gov (United States)

    Shin, Dayeon; Lee, Kyung Won; Kim, Mi-Hye; Kim, Hung Ju; An, Yun Sook; Chung, Hae-Kyung

    2018-01-09

    Diet plays a crucial role in cognitive function. Few studies have examined the relationship between dietary patterns and cognitive functions of older adults in the Korean population. This study aimed to identify the effect of dietary patterns on the risk of mild cognitive impairment. A total of 239 participants, including 88 men and 151 women, aged 65 years and older were selected from health centers in the district of Seoul, Gyeonggi province, and Incheon, in Korea. Dietary patterns were determined using Reduced Rank Regression (RRR) methods with responses regarding vitamin B6, vitamin C, and iron intakes, based on both a one-day 24-h recall and a food frequency questionnaire. Cognitive function was assessed using the Korean-Mini Mental State Examination (K-MMSE). Multivariable logistic regression models were used to estimate the association between dietary pattern score and the risk of mild cognitive impairment. A total of 20 (8%) out of the 239 participants had mild cognitive impairment. Three dietary patterns were identified: seafood and vegetables, high meat, and bread, ham, and alcohol. Among the three dietary patterns, the older adult population who adhered to the seafood and vegetables pattern, characterized by high intake of seafood, vegetables, fruits, bread, snacks, soy products, beans, chicken, pork, ham, egg, and milk had a decreased risk of mild cognitive impairment compared to those who did not (adjusted odds ratios 0.06, 95% confidence interval 0.01-0.72) after controlling for gender, supplementation, education, history of dementia, physical activity, body mass index (BMI), and duration of sleep. The other two dietary patterns were not significantly associated with the risk of mild cognitive impairment. In conclusion, high consumption of fruits, vegetables, seafood, and protein foods was significantly associated with reduced mild cognitive impairment in older Korean adults. These results can contribute to the establishment of dietary guidelines

  5. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits

    NARCIS (Netherlands)

    Hammerschlag, Anke R; Stringer, Sven; de Leeuw, Christiaan A; Sniekers, Suzanne; Taskesen, Erdogan; Watanabe, Kyoko; Blanken, Tessa F; Dekker, Kim; Te Lindert, Bart H W; Wassing, Rick; Jonsdottir, Ingileif; Thorleifsson, Gudmar; Stefansson, Hreinn; Gislason, Thorarinn; Berger, Klaus; Schormair, Barbara; Wellmann, Juergen; Winkelmann, Juliane; Stefansson, Kari; Oexle, Konrad; Van Someren, Eus J W; Posthuma, Danielle

    2017-01-01

    Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven

  6. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

    NARCIS (Netherlands)

    Stolk, Lisette; Perry, John R. B.; Chasman, Daniel I.; He, Chunyan; Mangino, Massimo; Sulem, Patrick; Barbalic, Maja; Broer, Linda; Byrne, Enda M.; Ernst, Florian; Esko, Tonu; Franceschini, Nora; Gudbjartsson, Daniel F.; Hottenga, Jouke-Jan; Kraft, Peter; McArdle, Patrick F.; Porcu, Eleonora; Shin, So-Youn; Smith, Albert V.; van Wingerden, Sophie; Zhai, Guangju; Zhuang, Wei V.; Albrecht, Eva; Alizadeh, Behrooz Z.; Aspelund, Thor; Bandinelli, Stefania; Lauc, Lovorka Barac; Beckmann, Jacques S.; Boban, Mladen; Boerwinkle, Eric; Broekmans, Frank J.; Burri, Andrea; Campbell, Harry; Chanock, Stephen J.; Chen, Constance; Cornelis, Marilyn C.; Corre, Tanguy; Coviello, Andrea D.; d'Adamo, Pio; Davies, Gail; de Faire, Ulf; de Geus, Eco J. C.; Deary, Ian J.; Dedoussis, George V. Z.; Deloukas, Panagiotis; Ebrahim, Shah; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan G.; Fauser, Bart C. J. M.; Ferreli, Liana; Ferrucci, Luigi; Fischer, Krista; Folsom, Aaron R.; Garcia, Melissa E.; Gasparini, Paolo; Gieger, Christian; Glazer, Nicole; Grobbee, Diederick E.; Hall, Per; Haller, Toomas; Hankinson, Susan E.; Hass, Merli; Hayward, Caroline; Heath, Andrew C.; Hofman, Albert; Ingelsson, Erik; Janssens, A. Cecile J. W.; Johnson, Andrew D.; Karasik, David; Kardia, Sharon L. R.; Keyzer, Jules; Kiel, Douglas P.; Kolcic, Ivana; Kutalik, Zoltan; Lahti, Jari; Lai, Sandra; Laisk, Triin; Laven, Joop S. E.; Lawlor, Debbie A.; Liu, Jianjun; Lopez, Lorna M.; Louwers, Yvonne V.; Magnusson, Patrik K. E.; Marongiu, Mara; Martin, Nicholas G.; Klaric, Irena Martinovic; Masciullo, Corrado; McKnight, Barbara; Medland, Sarah E.; Melzer, David; Mooser, Vincent; Navarro, Pau; Newman, Anne B.; Nyholt, Dale R.; Onland-Moret, N. Charlotte; Palotie, Aarno; Pare, Guillaume; Parker, Alex N.; Pedersen, Nancy L.; Peeters, Petra H. M.; Pistis, Giorgio; Plump, Andrew S.; Polasek, Ozren; Pop, Victor J. M.; Psaty, Bruce M.; Raikkonen, Katri; Rehnberg, Emil; Rotter, Jerome I.; Rudan, Igor; Sala, Cinzia; Salumets, Andres; Scuteri, Angelo; Singleton, Andrew; Smith, Jennifer A.; Snieder, Harold; Soranzo, Nicole; Stacey, Simon N.; Starr, John M.; Stathopoulou, Maria G.; Stirrups, Kathleen; Stolk, Ronald P.; Styrkarsdottir, Unnur; Sun, Yan V.; Tenesa, Albert; Thorand, Barbara; Toniolo, Daniela; Tryggvadottir, Laufey; Tsui, Kim; Ulivi, Sheila; van Dam, Rob M.; van der Schouw, Yvonne T.; van Gils, Carla H.; van Nierop, Peter; Vink, Jacqueline M.; Visscher, Peter M.; Voorhuis, Marlies; Waeber, Gerard; Wallaschofski, Henri; Wichmann, H. Erich; Widen, Elisabeth; Wijnands-van Gent, Colette J. M.; Willemsen, Gonneke; Wilson, James F.; Wolffenbuttel, Bruce H. R.; Wright, Alan F.; Yerges-Armstrong, Laura M.; Zemunik, Tatijana; Zgaga, Lina; Zillikens, M. Carola; Zygmunt, Marek; Arnold, Alice M.; Boomsma, Dorret I.; Buring, Julie E.; Crisponi, Laura; Demerath, Ellen W.; Gudnason, Vilmundur; Harris, Tamara B.; Hu, Frank B.; Hunter, David J.; Launer, Lenore J.; Metspalu, Andres; Montgomery, Grant W.; Oostra, Ben A.; Ridker, Paul M.; Sanna, Serena; Schlessinger, David; Spector, Tim D.; Stefansson, Kari; Streeten, Elizabeth A.; Thorsteinsdottir, Unnur; Uda, Manuela; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Voelzke, Henry; Murray, Anna; Murabito, Joanne M.; Visser, Jenny A.; Lunetta, Kathryn L.

    To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural

  7. Transcriptional profile analysis of RPGRORF15 frameshift mutation identifies novel genes associated with retinal degeneration.

    Science.gov (United States)

    Genini, Sem; Zangerl, Barbara; Slavik, Julianna; Acland, Gregory M; Beltran, William A; Aguirre, Gustavo D

    2010-11-01

    To identify genes and molecular mechanisms associated with photoreceptor degeneration in a canine model of XLRP caused by an RPGR exon ORF15 microdeletion. Methods. Expression profiles of mutant and normal retinas were compared by using canine retinal custom cDNA microarrays. qRT-PCR, Western blot analysis, and immunohistochemistry (IHC) were applied to selected genes, to confirm and expand the microarray results. At 7 and 16 weeks, respectively, 56 and 18 transcripts were downregulated in the mutant retinas, but none were differentially expressed (DE) at both ages, suggesting the involvement of temporally distinct pathways. Downregulated genes included the known retina-relevant genes PAX6, CHML, and RDH11 at 7 weeks and CRX and SAG at 16 weeks. Genes directly or indirectly active in apoptotic processes were altered at 7 weeks (CAMK2G, NTRK2, PRKCB, RALA, RBBP6, RNF41, SMYD3, SPP1, and TUBB2C) and 16 weeks (SLC25A5 and NKAP). Furthermore, the DE genes at 7 weeks (ELOVL6, GLOD4, NDUFS4, and REEP1) and 16 weeks (SLC25A5 and TARS2) are related to mitochondrial functions. qRT-PCR of 18 genes confirmed the microarray results and showed DE of additional genes not on the array. Only GFAP was DE at 3 weeks of age. Western blot and IHC analyses also confirmed the high reliability of the transcriptomic data. Several DE genes were identified in mutant retinas. At 7 weeks, a combination of nonclassic anti- and proapoptosis genes appear to be involved in photoreceptor degeneration, whereas at both 7 and 16 weeks, the expression of mitochondria-related genes indicates that they may play a relevant role in the disease process.

  8. Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis.

    Science.gov (United States)

    Hao, Jiangcan; Liu, Yang; Xu, Jiawen; Wang, Wenyu; Wen, Yan; He, Awen; Fan, Qianrui; Guo, Xiong; Zhang, Feng

    2017-07-25

    Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects. Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10 -6 , β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10 -3 , β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function. Our results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS.

  9. MrTADFinder: A network modularity based approach to identify topologically associating domains in multiple resolutions.

    Directory of Open Access Journals (Sweden)

    Koon-Kiu Yan

    2017-07-01

    Full Text Available Genome-wide proximity ligation based assays such as Hi-C have revealed that eukaryotic genomes are organized into structural units called topologically associating domains (TADs. From a visual examination of the chromosomal contact map, however, it is clear that the organization of the domains is not simple or obvious. Instead, TADs exhibit various length scales and, in many cases, a nested arrangement. Here, by exploiting the resemblance between TADs in a chromosomal contact map and densely connected modules in a network, we formulate TAD identification as a network optimization problem and propose an algorithm, MrTADFinder, to identify TADs from intra-chromosomal contact maps. MrTADFinder is based on the network-science concept of modularity. A key component of it is deriving an appropriate background model for contacts in a random chain, by numerically solving a set of matrix equations. The background model preserves the observed coverage of each genomic bin as well as the distance dependence of the contact frequency for any pair of bins exhibited by the empirical map. Also, by introducing a tunable resolution parameter, MrTADFinder provides a self-consistent approach for identifying TADs at different length scales, hence the acronym "Mr" standing for Multiple Resolutions. We then apply MrTADFinder to various Hi-C datasets. The identified domain boundaries are marked by characteristic signatures in chromatin marks and transcription factors (TF that are consistent with earlier work. Moreover, by calling TADs at different length scales, we observe that boundary signatures change with resolution, with different chromatin features having different characteristic length scales. Furthermore, we report an enrichment of HOT (high-occupancy target regions near TAD boundaries and investigate the role of different TFs in determining boundaries at various resolutions. To further explore the interplay between TADs and epigenetic marks, as tumor mutational

  10. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited

    DEFF Research Database (Denmark)

    Deelen, Joris; Beekman, Marian; Uh, Hae-Won

    2011-01-01

    (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P ... genome-wide significance with survival into old age in the meta-analysis of 4149 nonagenarian cases and 7582 younger controls (OR = 0.71 (95% CI 0.65-0.77), P = 3.39 x 10(-17) ). This SNP, rs2075650, is located in TOMM40 at chromosome 19q13.32 close to the apolipoprotein E (APOE) gene. Although...... of the nonagenarian cases from the LLS and their partners. In addition, we observed a novel association between this locus and serum levels of IGF-1 in females (P = 0.005). In conclusion, the major locus determining familial longevity up to high age as detected by GWAS was marked by rs2075650, which tags...

  11. Genome-wide association study identifies loci affecting blood copper, selenium and zinc.

    Science.gov (United States)

    Evans, David M; Zhu, Gu; Dy, Veronica; Heath, Andrew C; Madden, Pamela A F; Kemp, John P; McMahon, George; St Pourcain, Beate; Timpson, Nicholas J; Golding, Jean; Lawlor, Debbie A; Steer, Colin; Montgomery, Grant W; Martin, Nicholas G; Smith, George Davey; Whitfield, John B

    2013-10-01

    Genetic variation affecting absorption, distribution or excretion of essential trace elements may lead to health effects related to sub-clinical deficiency. We have tested for allelic effects of single-nucleotide polymorphisms (SNPs) on blood copper, selenium and zinc in a genome-wide association study using two adult cohorts from Australia and the UK. Participants were recruited in Australia from twins and their families and in the UK from pregnant women. We measured erythrocyte Cu, Se and Zn (Australian samples) or whole blood Se (UK samples) using inductively coupled plasma mass spectrometry. Genotyping was performed with Illumina chips and > 2.5 m SNPs were imputed from HapMap data. Genome-wide significant associations were found for each element. For Cu, there were two loci on chromosome 1 (most significant SNPs rs1175550, P = 5.03 × 10(-10), and rs2769264, P = 2.63 × 10(-20)); for Se, a locus on chromosome 5 was significant in both cohorts (combined P = 9.40 × 10(-28) at rs921943); and for Zn three loci on chromosomes 8, 15 and X showed significant results (rs1532423, P = 6.40 × 10(-12); rs2120019, P = 1.55 × 10(-18); and rs4826508, P = 1.40 × 10(-12), respectively). The Se locus covers three genes involved in metabolism of sulphur-containing amino acids and potentially of the analogous Se compounds; the chromosome 8 locus for Zn contains multiple genes for the Zn-containing enzyme carbonic anhydrase. Where potentially relevant genes were identified, they relate to metabolism of the element (Se) or to the presence at high concentration of a metal-containing protein (Cu).

  12. Kinematic analysis quantifies gait abnormalities associated with lameness in broiler chickens and identifies evolutionary gait differences.

    Directory of Open Access Journals (Sweden)

    Gina Caplen

    Full Text Available This is the first time that gait characteristics of broiler (meat chickens have been compared with their progenitor, jungle fowl, and the first kinematic study to report a link between broiler gait parameters and defined lameness scores. A commercial motion-capturing system recorded three-dimensional temporospatial information during walking. The hypothesis was that the gait characteristics of non-lame broilers (n = 10 would be intermediate to those of lame broilers (n = 12 and jungle fowl (n = 10, tested at two ages: immature and adult. Data analysed using multi-level models, to define an extensive range of baseline gait parameters, revealed inter-group similarities and differences. Natural selection is likely to have made jungle fowl walking gait highly efficient. Modern broiler chickens possess an unbalanced body conformation due to intense genetic selection for additional breast muscle (pectoral hypertrophy and whole body mass. Together with rapid growth, this promotes compensatory gait adaptations to minimise energy expenditure and triggers high lameness prevalence within commercial flocks; lameness creating further disruption to the gait cycle and being an important welfare issue. Clear differences were observed between the two lines (short stance phase, little double-support, low leg lift, and little back displacement in adult jungle fowl; much double-support, high leg lift, and substantial vertical back movement in sound broilers presumably related to mass and body conformation. Similarities included stride length and duration. Additional modifications were also identified in lame broilers (short stride length and duration, substantial lateral back movement, reduced velocity presumably linked to musculo-skeletal abnormalities. Reduced walking velocity suggests an attempt to minimise skeletal stress and/or discomfort, while a shorter stride length and time, together with longer stance and double-support phases, are associated

  13. Identifying patient safety problems associated with information technology in general practice: an analysis of incident reports.

    Science.gov (United States)

    Magrabi, Farah; Liaw, Siaw Teng; Arachi, Diana; Runciman, William; Coiera, Enrico; Kidd, Michael R

    2016-11-01

    To identify the categories of problems with information technology (IT), which affect patient safety in general practice. General practitioners (GPs) reported incidents online or by telephone between May 2012 and November 2013. Incidents were reviewed against an existing classification for problems associated with IT and the clinical process impacted. 87 GPs across Australia. Types of problems, consequences and clinical processes. GPs reported 90 incidents involving IT which had an observable impact on the delivery of care, including actual patient harm as well as near miss events. Practice systems and medications were the most affected clinical processes. Problems with IT disrupted clinical workflow, wasted time and caused frustration. Issues with user interfaces, routine updates to software packages and drug databases, and the migration of records from one package to another generated clinical errors that were unique to IT; some could affect many patients at once. Human factors issues gave rise to some errors that have always existed with paper records but are more likely to occur and cause harm with IT. Such errors were linked to slips in concentration, multitasking, distractions and interruptions. Problems with patient identification and hybrid records generated errors that were in principle no different to paper records. Problems associated with IT include perennial risks with paper records, but additional disruptions in workflow and hazards for patients unique to IT, occasionally affecting multiple patients. Surveillance for such hazards may have general utility, but particularly in the context of migrating historical records to new systems and software updates to existing systems. 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/.

  14. Identified particle yield associated with a high-$p_T$ trigger particle at the LHC

    CERN Document Server

    Veldhoen, Misha; van Leeuwen, Marco

    Identified particle production ratios are important observables, used to constrain models of particle production in heavy-ion collisions. Measurements of the inclusive particle ratio in central heavy-ion collisions showed an increase of the baryon-to-meson ratio compared to proton-proton collisions at intermediate pT, the so-called baryon anomaly. One possible explanation of the baryon anomaly is that partons from the thermalized deconfined QCD matter hadronize in a different way compared to hadrons produced in a vacuum jet. In this work we extend on previous measurements by measuring particle ratios in the yield associated with a high-pT trigger particle. These measurements can potentially further constrain the models of particle production since they are sensitive to the difference between particles from a jet and particles that are produced in the bulk. We start by developing a particle identification method that uses both the specific energy loss of a particle and the time of flight. From there, we presen...

  15. Using naturalistic driving data to identify variables associated with infrequent, occasional, and consistent seat belt use.

    Science.gov (United States)

    Reagan, Ian J; McClafferty, Julie A; Berlin, Sharon P; Hankey, Jonathan M

    2013-01-01

    Seat belt use is one of the most effective countermeasures to reduce traffic fatalities and injuries. The success of efforts to increase use is measured by road side observations and self-report questionnaires. These methods have shortcomings, with the former requiring a binary point estimate and the latter being subjective. The 100-car naturalistic driving study presented a unique opportunity to study seat belt use in that seat belt status was known for every trip each driver made during a 12-month period. Drivers were grouped into infrequent, occasional, or consistent seat belt users based on the frequency of belt use. Analyses were then completed to assess if these groups differed on several measures including personality, demographics, self-reported driving style variables as well as measures from the 100-car study instrumentation suite (average trip speed, trips per day). In addition, detailed analyses of the occasional belt user group were completed to identify factors that were predictive of occasional belt users wearing their belts. The analyses indicated that consistent seat belt users took fewer trips per day, and that increased average trip speed was associated with increased belt use among occasional belt users. The results of this project may help focus messaging efforts to convert occasional and inconsistent seat belt users to consistent users. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Conceptual and Operational Considerations in Identifying Socioenvironmental Factors Associated with Disability among Community-Dwelling Adults

    Directory of Open Access Journals (Sweden)

    Mathieu Philibert

    2015-04-01

    Full Text Available Disability is conceived as a person–context interaction. Physical and social environments are identified as intervention targets for improving social participation and independence. In comparison to the body of research on place and health, relatively few reports have been published on residential environments and disability in the health sciences literature. We reviewed studies evaluating the socioenvironmental correlates of disability. Searches were conducted in Medline, Embase and CINAHL databases for peer-reviewed articles published between 1997 and 2014. We found many environmental factors to be associated with disability, particularly area-level socioeconomic status and rurality. However, diversity in conceptual and methodological approaches to such research yields a limited basis for comparing studies. Conceptual inconsistencies in operational measures of disability and conceptual disagreement between studies potentially affect understanding of socioenvironmental influences. Similarly, greater precision in socioenvironmental measures and in study designs are likely to improve inference. Consistent and generalisable support for socioenvironmental influences on disability in the general adult population is scarce.

  17. Genome-Wide Analysis to Identify HLA Factors Potentially Associated With Severe Dengue

    Directory of Open Access Journals (Sweden)

    Sudheer Gupta

    2018-04-01

    Full Text Available The pathogenesis of dengue hemorrhagic fever (DHF, following dengue virus (DENV infection, is a complex and poorly understood phenomenon. In view of the clinical need of identifying patients with higher likelihood of developing this severe outcome, we undertook a comparative genome-wide association analysis of epitope variants from sequences available in the ViPR database that have been reported to be differentially related to dengue fever and DHF. Having enumerated the incriminated epitope variants, we determined the corresponding HLA alleles in the context of which DENV infection could potentially precipitate DHF. Our analysis considered the development of DHF in three different perspectives: (a as a consequence of primary DENV infection, (b following secondary DENV infection with a heterologous serotype, (c as a result of DENV infection following infection with related flaviviruses like Zika virus, Japanese Encephalitis virus, West Nile virus, etc. Subject to experimental validation, these viral and host markers would be valuable in triaging DENV-infected patients for closer supervision owing to the relatively higher risk of poor prognostic outcome and also for the judicious allocation of scarce institutional resources during large outbreaks.

  18. Hemoglobin to Hematocrit Ratio: The Strongest Predictor of Femoral Head Osteonecrosis in Children With Sickle Cell Disease.

    Science.gov (United States)

    Worrall, Douglas; Smith-Whitley, Kim; Wells, Lawrence

    2016-03-01

    Femoral head osteonecrosis (ON) secondary to sickle cell disease (SCD) often progresses to femoral head collapse, requiring total hip arthroplasty. However, this treatment has a limited durability and patients with SCD have higher rates of complications, requiring multiple revision operations. Identifying risk factors linked to ON in SCD can facilitate earlier precollapse diagnosis and surgical treatment aimed at preservation of the native hip joint. Fifty-nine children treated at our institution between January 2001 and April 2012 with SCD and ON, as diagnosed by magnetic resonance imaging or radiographic imaging, were compared with age-matched and sickle cell phenotype-matched (SS, SC, Sβ, Sβ) controls with no evidence of ON. Two sided t-tests assuming unequal variances determined statistically risk factors and threshold values were assigned to calculate odds ratios. Systolic blood pressure (P=1.2×10, OR=3.68), diastolic blood pressure (P=0.0084, OR=1.41), weight in the SCD-SS population (P=0.04, OR=1.85), and hemoglobin (Hb) in the SCD-SS population (P=0.036, OR=2.56) were elevated in cases. Curiously, dividing the Hb by the hematocrit to serve as a clinical proxy for the mean corpuscular Hb concentration (MCHC) produced an excellent predictor of ON (P=2.06×10, OR=5.17), which was especially pronounced in the SCD-SS subpopulation (P=2.28×10, OR=8.65). Among children with SCD, the overall prevalence of ON was 9% (59/658) and the phenotype with the highest prevalence of ON was Sβ thalassemia with an ON prevalence of 11.1%. There was no observed correlation between ON and height, body mass index, cholesterol, mean corpuscular volume, hematocrit, or glucocorticoid use. These data support a novel clinical marker, the MCHC proxy, as the strongest predictor of ON in children with SCD. High-risk children should receive hip magnetic resonance imaging to diagnose early ON and facilitate interventions focused on hip preservation, forestalling, or possibly preventing

  19. Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

    DEFF Research Database (Denmark)

    Webb, Thomas R; Erdmann, Jeanette; Stirrups, Kathleen E

    2017-01-01

    BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variant...

  20. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

    DEFF Research Database (Denmark)

    Anderson, Carl A; Boucher, Gabrielle; Lees, Charlie W

    2011-01-01

    Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association s...

  1. Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk

    NARCIS (Netherlands)

    X. Guo (Xingyi); J. Long (Jirong); C. Zeng (Chenjie); K. Michailidou (Kyriaki); M. Ghoussaini (Maya); M.K. Bolla (Manjeet); Q. Wang (Qing); R.L. Milne (Roger L.); X.-O. Shu (Xiao-Ou); Q. Cai (Qiuyin); J. Beesley (Jonathan); S. Kar (Siddhartha); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); V. Arndt (Volker); M.W. Beckmann (Matthias); A. Beeghly-Fadiel (Alicia); J. Benítez (Javier); W.J. Blot (William); N.V. Bogdanova (Natalia); S.E. Bojesen (Stig); H. Brauch (Hiltrud); H. Brenner (Hermann); L.A. Brinton (Louise); A. Broekss (Annegien); T. Brüning (Thomas); B. Burwinkel (Barbara); H. Cai (Hui); S. Canisius (Sander); J. Chang-Claude (Jenny); J.-Y. Choi (J.); F.J. Couch (Fergus); A. Cox (Angela); S.S. Cross (Simon); K. Czene (Kamila); H. Darabi (Hatef); P. Devilee (Peter); A. Droit (Arnaud); T. Dörk (Thilo); P.A. Fasching (Peter); O. Fletcher (Olivia); H. Flyger (Henrik); F. Fostira (Florentia); V. Gaborieau (Valerie); M. García-Closas (Montserrat); G.G. Giles (Graham G.); M. Grip (Mervi); P. Guénel (Pascal); C.A. Haiman (Christopher A.); U. Hamann (Ute); J.M. Hartman (Joost); A. Hollestelle (Antoinette); J.L. Hopper (John L.); C.-N. Hsiung (Chia-Ni); H. Ito (Hidemi); A. Jakubowska (Anna); N. Johnson (Nichola); M. Kabisch (Maria); D. Kang (Daehee); S. Khan (Sofia); J.A. Knight (Julia); V-M. Kosma (Veli-Matti); D. Lambrechts (Diether); L. Le Marchand (Loic); J. Li (Jingmei); A. Lindblom (Annika); A. Lophatananon (Artitaya); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); S. Margolin (Sara); F. Marme (Federick); K. Matsuo (Keitaro); C.A. McLean (Catriona Ann); A. Meindl (Alfons); K. Muir (Kenneth); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); J.E. Olson (Janet); N. Orr (Nick); P. Peterlongo (Paolo); T.C. Putti (Thomas Choudary); A. Rudolph (Anja); S. Sangrajrang (Suleeporn); E.J. Sawyer (Elinor); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); C-Y. Shen (Chen-Yang); J. Shi (Jiajun); M. Shrubsole (Martha); M.C. Southey (Melissa); A.J. Swerdlow (Anthony ); S.H. Teo (Soo Hwang); B. Thienpont (Bernard); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I. Tomlinson (Ian); T. Truong (Thérèse); C.-C. Tseng (Chiu-chen); A.M.W. van den Ouweland (Ans); W. Wen (Wanqing); R. Winqvist (Robert); A. Wu (Anna); C.H. Yip (Cheng Har); M.P. Zamora (Pilar); Y. Zheng (Ying); P. Hall (Per); P.D.P. Pharoah (Paul); J. Simard (Jacques); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); D.F. Easton (Douglas F.); W. Zheng (Wei); R. Eeles (Rosalind); A.A. Al Olama (Ali Amin); Z. Kote-Jarai; S. Benlloch (Sara); A.C. Antoniou (Antonis C.); L. McGuffog (Lesley); K. Offit (Kenneth); A. Lee (Andrew); E. Dicks (Ed); C. Luccarini (Craig); D.C. Tessier (Daniel C.); F. Bacot (Francois); D. Vincent (Daniel); S. La Boissière (Sylvie); F. Robidoux (Frederic); S.F. Nielsen (Sune); J.M. Cunningham (Julie); S.A. Windebank (Sharon A.); C.A. Hilker (Christopher A.); J. Meyer (Jeffrey); M. Angelakos (Maggie); J. Maskiell (Judi); E.J. Rutgers (Emiel J.); S. Verhoef; F.B.L. Hogervorst (Frans); P. Boonyawongviroj (Prat); P. Siriwanarungsan (Pornthep); A. Schrauder (André); M. Rübner (Matthias); S. Oeser (Sonja); S. Landrith (Silke); E. Williams (Eileen); E. Ryder-Mills (Elaine); K. Sargus (Kara); N. McInerney (Niall); G. Colleran (Gabrielle); A. Rowan (Andrew); A. Jones (Angela); C. Sohn (Christof); A. Schneeweiß (Andeas); P. Bugert (Peter); N. Álvarez (Nuria); L. Bernstein (Leslie); J. Lacey (James); S. Wang (Sophia); H. Ma (Huiyan); Y. Lu (Yani); J. Clague De Hart (Jessica); D. Deapen (Dennis); R. Pinder (Rich); E. Lee (Eunjung); F.R. Schumacher (Fredrick); P. Horn-Ross (Pam); P. Reynolds (Peggy); D. Nelson (David); H. Park (Hannah); H. Ziegler (Hartwig); S. Wolf (Sonja); V. Hermann (Volker); W.-Y. Lo (Wing-Yee); C. Justenhoven (Christina); Y.-D. Ko (Yon-Dschun); C. Baisch (Christian); H.-P. Fischer (Hans-Peter); B. Pesch (Beate); S. Rabstein (Sylvia); A. Lotz (Anne); V. Harth (Volker); T. Heikkinen (Tuomas); I. Erkkilä (Irja); K. Aaltonen (Kirsimari); K. von Smitten (Karl); N.N. Antonenkova (Natalia); P. Hillemanns (Peter); H. Christiansen (Hans); E. Myöhänen (Eija); H. Kemiläinen (Helena); H. Thorne (Heather); E. Niedermayr (Eveline); D. Bowtell; G. Chenevix-Trench (Georgia); A. De Fazio (Anna); D. Gertig; A. Green; P. Webb (Penny); A. Green; P. Parsons; N. Hayward; P.M. Webb (P.); D. Whiteman; A. Fung (Annie); J. Yashiki (June); G. Peuteman (Gilian); D. Smeets (Dominiek); T. Van Brussel (Thomas); K. Corthouts (Kathleen); N. Obi (Nadia); J. Heinz (Judith); T.W. Behrens (Timothy); U. Eilber (Ursula); M. Celik (Muhabbet); T. Olchers (Til); B. Peissel (Bernard); G. Scuvera (Giulietta); D. Zaffaroni (Daniela); B. Bonnani (Bernardo); I. Feroce (Irene); A. Maniscalco (Angela); A. Rossi (Alessandra); L. Bernard (Loris); M. Tranchant (Martine); M.-F. Valois (Marie-France); A. Turgeon (Annie); L. Heguy (Lea); P.S. Yee (Phuah Sze); P. Kang (Peter); K.I. Nee (Kang In); S. Mariapun (Shivaani); Y. Sook-Yee (Yoon); D.S.C. Lee (Daphne S.C.); T.Y. Ching (Teh Yew); N.A.M. Taib (Nur Aishah Mohd); M. Otsukka (Meeri); K. Mononen (Kari); T. Selander (Teresa); N. Weerasooriya (Nayana); E.M.M. Krol-Warmerdam (Elly); J. Molenaar; J. Blom; N. Szeszenia-Dabrowska (Neonilia); B. Peplonska (Beata); W. Zatonski (Witold); P. Chao (Pei); M. Stagner (Michael); P. Bos (Petra); J. Blom (Jannet); E. Crepin (Ellen); A. Nieuwlaat (Anja); A. Heemskerk (Annette); S. Higham (Sue); H.E. Cramp (Helen); D. Connley (Daniel); S. Balasubramanian (Sabapathy); I.W. Brock (Ian); M. Kerin (Michael); N. Miller (Nicola); P. Kerbrat (Pierre); P. Arveux (Patrick); R. Le Scodan (Romuald); Y. Raoul (Yves); P. Laurent-Puig (Pierre); C. Mulot (Claire); C. Stegmaier (Christa); K. Butterbach (Katja); J.H. Karstens (Johann); D. Flesch-Janys (Dieter); P. Seibold (Petra); A. Vrieling (Alina); S. Nickels (Stefan); P. Radice (Paolo); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); D. Conroy (Don); C. Baynes (Caroline); K. Chua (Kimberley); R. Pilarski (Robert)

    2015-01-01

    textabstractBackground: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540

  2. AP diameter shows the strongest correlation with CTDI and DLP in abdominal and chest CT.

    LENUS (Irish Health Repository)

    Zarb, Francis

    2010-01-01

    The purpose of this study is to investigate the relationships among cross-sectional diameters, weight and computed tomography (CT) dose descriptors (CTDI and DLP) to identify which is best used as a measure for the establishment of DRLs in CT. Data (gender, weight, cross-sectional diameters, dose descriptors) from 56 adult patients attending for either a CT examination of the abdomen or chest was obtained from two spiral CT units using automatic milliampere modulation. The AP diameter was demonstrated as the main contributing factor influencing the dose in CT (CTDI: r(2) = 0.269, p-value < or =0.001; DLP: r(2) = 0.260, p-value < or =0.001) since it has a greater correlation with radiation dose than body weight and can thus be its substitute in dose-reduction strategies and establishment of DRLs. The advantages of using the AP diameter are that it can easily be measured prior to scanning or retrospectively from previous CT images. However, further studies on the practicality of this approach are recommended.

  3. AP diameter shows the strongest correlation with CTDI and DLP in abdominal and chest CT

    International Nuclear Information System (INIS)

    Zarb, F.; Rainford, L.; McEntee, M. F.

    2010-01-01

    The purpose of this study is to investigate the relationships among cross-sectional diameters, weight and computed tomography (CT) dose descriptors (CTDI and DLP) to identify which is best used as a measure for the establishment of DRLs in CT. Data (gender, weight, cross-sectional diameters, dose descriptors) from 56 adult patients attending for either a CT examination of the abdomen or chest was obtained from two spiral CT units using automatic milli-ampere modulation. The AP diameter was demonstrated as the main contributing factor influencing the dose in CT (CTDI: r 2 = 0.269, p-value ≤0.001; DLP: r 2 = 0.260, p-value ≤0.001) since it has a greater correlation with radiation dose than body weight and can thus be its substitute in dose-reduction strategies and establishment of DRLs. The advantages of using the AP diameter are that it can easily be measured prior to scanning or retrospectively from previous CT images. However, further studies on the practicality of this approach are recommended. (authors)

  4. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

    DEFF Research Database (Denmark)

    Amin Al Olama, Ali; Kote-Jarai, Zsofia; Schumacher, Fredrick R

    2013-01-01

    Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS inc...

  5. Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Sonia Paco

    Full Text Available Ullrich congenital muscular dystrophy (UCMD, caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered.

  6. Identifying sugarcane expressed sequences associated with nutrient transporters and peptide metal chelators

    Directory of Open Access Journals (Sweden)

    Antonio Figueira

    2001-12-01

    major plant metal-chelator peptide metallothionein (MT were identified: Type I MT being the most abundant (>1% of seed-library reads, followed by Type II which had a similar pattern of expression as that described for Arabidopsis MT. Identifying and understanding the expression of genes associated with nutrient uptake and metal tolerance could lead to the development of more nutrient-efficient sugarcane cultivars, or might allow the use of sugarcane as a hyper-accumulator plant for the restoration of contaminated areas in phytoremediation programs.A absorção de nutrientes pelas plantas é um processo ativo, requerendo energia para o acúmulo de nutrientes essenciais em níveis mais elevados nos tecidos vegetais do que na solução do solo, enquanto que a presença de metais tóxicos ou excesso de nutrientes requererem mecanismos para modular o acúmulo de íons. Genes que codificam transportadores de íons, isolados de plantas e de leveduras, foram usados para identificar homólogos presumíveis no banco de dados de seqüências expressas de cana-de-açúcar (SUCEST. Cinco consensos de grupos de seqüências com homologia a genes de transportadores de fosfato de alta afinidade foram identificados. O consenso de um dos grupos permitiu a predição da proteína completa, com 541 amino ácidos e 81% de identidade com o gene NtPT1 de Nicotiana tabacum, consistindo de 12 domínios transmembrana divididos por uma grande região hidrofílica. Homólogos presumíveis a genes transportadores de micronutrientes de Arabidopsis thaliana também foram detectados em algumas bibliotecas do SUCEST. A absorção de ferro em gramíneas envolve a liberação de um composto fito-sideróforo, ácido mugenêico (MA, que complexa com Fe3+, sendo então absorvido por um transportador específico. Seqüências expressas (EST, expressed sequence tag de cana-de-açúcar homólogas aos genes que codificam as três enzimas da via de biossíntese do ácido mugenêico (nicotianamina sintase

  7. D90: The Strongest Contributor to Setting Time in Mineral Trioxide Aggregate and Portland Cement.

    Science.gov (United States)

    Ha, William N; Bentz, Dale P; Kahler, Bill; Walsh, Laurence J

    2015-07-01

    The setting times of commercial mineral trioxide aggregate (MTA) and Portland cements vary. It was hypothesized that much of this variation was caused by differences in particle size distribution. Two gram samples from 11 MTA-type cements were analyzed by laser diffraction to determine their particle size distributions characterized by their percentile equivalent diameters (the 10th percentile, the median, and the 90th percentile [d90], respectively). Setting time data were received from manufacturers who performed indentation setting time tests as specified by the standards relevant to dentistry, ISO 6786 (9 respondents) or ISO 9917.1 (1 respondent), or not divulged to the authors (1 respondent). In a parallel experiment, 6 samples of different size graded Portland cements were produced using the same cement clinker. The measurement of setting time for Portland cement pastes was performed using American Society for Testing and Materials C 191. Cumulative heat release was measured using isothermal calorimetry to assess the reactions occurring during the setting of these pastes. In all experiments, linear correlations were assessed between setting times, heat release, and the 3 particle size parameters. Particle size varied considerably among MTA cements. For MTA cements, d90 was the particle size characteristic showing the highest positive linear correlation with setting time (r = 0.538). For Portland cement, d90 gave an even higher linear correlation for the initial setting time (r = 0.804) and the final setting time (r = 0.873) and exhibited a strong negative linear correlation for cumulative heat release (r = 0.901). Smaller particle sizes result in faster setting times, with d90 (the largest particles) being most closely correlated with the setting times of the samples. Copyright © 2015 American Association of Endodontists. All rights reserved.

  8. A genetic and genomic analysis identifies a cluster of genes associated with hematopoietic cell turnover

    NARCIS (Netherlands)

    de Haan, G; Bystrykh, LV; Weersing, E; Dontje, B; Geiger, H; Ivanova, N; Lemischka, IR; Vellenga, E; Van Zant, G

    2002-01-01

    Hematopoietic stem cells from different strains of mice vary widely with respect to their cell cycle activity. In the present study we used complementary genetic and genomic approaches to identify molecular pathways affecting this complex trait. We identified a major quantitative trait locus (QTL)

  9. Proteomic characterization of circulating extracellular vesicles identifies novel serum myeloma associated markers.

    Science.gov (United States)

    Harshman, Sean W; Canella, Alessandro; Ciarlariello, Paul D; Agarwal, Kitty; Branson, Owen E; Rocci, Alberto; Cordero, Hector; Phelps, Mitch A; Hade, Erinn M; Dubovsky, Jason A; Palumbo, Antonio; Rosko, Ashley; Byrd, John C; Hofmeister, Craig C; Benson, Don M; Paulaitis, Michael E; Freitas, Michael A; Pichiorri, Flavia

    2016-03-16

    Multiple myeloma (MM) is a hematological malignancy of clonal plasma cells in the bone marrow (BM). The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of extracellular vesicles (EVs). The aim of this manuscript is to use proteomic profiling of EVs as a tool to identify circulating tumor associated markers in MM patients. First, we characterized the EV protein content obtained from different MM cell lines. Then, we established differences in protein abundance among EVs isolated from MM patient serum and BM and the serum of healthy donors. These data show that the Major Histocompatibility Complex Class I is highly enriched in EVs of MM cell lines and MM patient's serum. Next, we show that CD44 is highly expressed in the EVs isolated from the corticosteroid resistant MM cell line, MM.1R. Furthermore, CD44 was found to be differentially expressed in EVs isolated from newly diagnosed MM patients. Finally through ELISA analysis, we establish the potential of serum CD44 as a predictive biomarker of overall survival. These results support the analysis of EVs as an easily accessible source for MM biomarkers. Extracellular vesicles are becoming a research focus due to their roles in cancer cell biology such as immune evasion, therapeutic resistance, proliferation and metastases. While numerous studies of vesicle characterization and biology have been conducted in many cancer models, the role of EV in MM remains relatively unstudied. Here we found that EVs isolated from MM cells are enriched in MHC-1 antigen presenting complex and its binding protein β2-MG, this observation is compatible with the enhanced proteasome activity of MM cells compared to other cancers and the ability of functional MHC-1 to bind and present peptides, generated from protein degradation by the proteasome. Additionally, our experiments show that CD44 is particularly enriched in the EV fraction

  10. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism

    DEFF Research Database (Denmark)

    Sapkota, Yadav; Steinthorsdottir, Valgerdur; Morris, Andrew P

    2017-01-01

    Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17,045 endomet......Endometriosis is a heritable hormone-dependent gynecological disorder, associated with severe pelvic pain and reduced fertility; however, its molecular mechanisms remain largely unknown. Here we perform a meta-analysis of 11 genome-wide association case-control data sets, totalling 17......,045 endometriosis cases and 191,596 controls. In addition to replicating previously reported loci, we identify five novel loci significantly associated with endometriosis risk (P... identified five secondary association signals, including two at the ESR1 locus, resulting in 19 independent single nucleotide polymorphisms (SNPs) robustly associated with endometriosis, which together explain up to 5.19% of variance in endometriosis. These results highlight novel variants in or near...

  11. Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR gene.

    Directory of Open Access Journals (Sweden)

    Karen Kapur

    2010-07-01

    Full Text Available Calcium has a pivotal role in biological functions, and serum calcium levels have been associated with numerous disorders of bone and mineral metabolism, as well as with cardiovascular mortality. Here we report results from a genome-wide association study of serum calcium, integrating data from four independent cohorts including a total of 12,865 individuals of European and Indian Asian descent. Our meta-analysis shows that serum calcium is associated with SNPs in or near the calcium-sensing receptor (CASR gene on 3q13. The top hit with a p-value of 6.3 x 10(-37 is rs1801725, a missense variant, explaining 1.26% of the variance in serum calcium. This SNP had the strongest association in individuals of European descent, while for individuals of Indian Asian descent the top hit was rs17251221 (p = 1.1 x 10(-21, a SNP in strong linkage disequilibrium with rs1801725. The strongest locus in CASR was shown to replicate in an independent Icelandic cohort of 4,126 individuals (p = 1.02 x 10(-4. This genome-wide meta-analysis shows that common CASR variants modulate serum calcium levels in the adult general population, which confirms previous results in some candidate gene studies of the CASR locus. This study highlights the key role of CASR in calcium regulation.

  12. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Sleiman, Patrick; Nielsen, Kasper

    2014-01-01

    years of age in a total of 1,173 cases and 2,522 controls. Cases were identified from national health registries of hospitalization, and DNA was obtained from the Danish Neonatal Screening Biobank. We identified five loci with genome-wide significant association. Four of these, GSDMB, IL33, RAD50 and IL...

  13. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    OpenAIRE

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Renter��a, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivi��res, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjus...

  14. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

    DEFF Research Database (Denmark)

    Orr, Nick; Lemnrau, Alina; Cooke, Rosie

    2012-01-01

    We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P ...

  15. The compact Selaginella genome identifies changes in gene content associated with the evolution of vascular plants

    Energy Technology Data Exchange (ETDEWEB)

    Grigoriev, Igor V.; Banks, Jo Ann; Nishiyama, Tomoaki; Hasebe, Mitsuyasu; Bowman, John L.; Gribskov, Michael; dePamphilis, Claude; Albert, Victor A.; Aono, Naoki; Aoyama, Tsuyoshi; Ambrose, Barbara A.; Ashton, Neil W.; Axtell, Michael J.; Barker, Elizabeth; Barker, Michael S.; Bennetzen, Jeffrey L.; Bonawitz, Nicholas D.; Chapple, Clint; Cheng, Chaoyang; Correa, Luiz Gustavo Guedes; Dacre, Michael; DeBarry, Jeremy; Dreyer, Ingo; Elias, Marek; Engstrom, Eric M.; Estelle, Mark; Feng, Liang; Finet, Cedric; Floyd, Sandra K.; Frommer, Wolf B.; Fujita, Tomomichi; Gramzow, Lydia; Gutensohn, Michael; Harholt, Jesper; Hattori, Mitsuru; Heyl, Alexander; Hirai, Tadayoshi; Hiwatashi, Yuji; Ishikawa, Masaki; Iwata, Mineko; Karol, Kenneth G.; Koehler, Barbara; Kolukisaoglu, Uener; Kubo, Minoru; Kurata, Tetsuya; Lalonde, Sylvie; Li, Kejie; Li, Ying; Litt, Amy; Lyons, Eric; Manning, Gerard; Maruyama, Takeshi; Michael, Todd P.; Mikami, Koji; Miyazaki, Saori; Morinaga, Shin-ichi; Murata, Takashi; Mueller-Roeber, Bernd; Nelson, David R.; Obara, Mari; Oguri, Yasuko; Olmstead, Richard G.; Onodera, Naoko; Petersen, Bent Larsen; Pils, Birgit; Prigge, Michael; Rensing, Stefan A.; Riano-Pachon, Diego Mauricio; Roberts, Alison W.; Sato, Yoshikatsu; Scheller, Henrik Vibe; Schulz, Burkhard; Schulz, Christian; Shakirov, Eugene V.; Shibagaki, Nakako; Shinohara, Naoki; Shippen, Dorothy E.; Sorensen, Iben; Sotooka, Ryo; Sugimoto, Nagisa; Sugita, Mamoru; Sumikawa, Naomi; Tanurdzic, Milos; Theilsen, Gunter; Ulvskov, Peter; Wakazuki, Sachiko; Weng, Jing-Ke; Willats, William W.G.T.; Wipf, Daniel; Wolf, Paul G.; Yang, Lixing; Zimmer, Andreas D.; Zhu, Qihui; Mitros, Therese; Hellsten, Uffe; Loque, Dominique; Otillar, Robert; Salamov, Asaf; Schmutz, Jeremy; Shapiro, Harris; Lindquist, Erika; Lucas, Susan; Rokhsar, Daniel

    2011-04-28

    We report the genome sequence of the nonseed vascular plant, Selaginella moellendorffii, and by comparative genomics identify genes that likely played important roles in the early evolution of vascular plants and their subsequent evolution

  16. Applying MetaMap to Medline for identifying novel associations in a large clinical dataset: a feasibility analysis.

    Science.gov (United States)

    Hanauer, David A; Saeed, Mohammed; Zheng, Kai; Mei, Qiaozhu; Shedden, Kerby; Aronson, Alan R; Ramakrishnan, Naren

    2014-01-01

    We describe experiments designed to determine the feasibility of distinguishing known from novel associations based on a clinical dataset comprised of International Classification of Disease, V.9 (ICD-9) codes from 1.6 million patients by comparing them to associations of ICD-9 codes derived from 20.5 million Medline citations processed using MetaMap. Associations appearing only in the clinical dataset, but not in Medline citations, are potentially novel. Pairwise associations of ICD-9 codes were independently identified in both the clinical and Medline datasets, which were then compared to quantify their degree of overlap. We also performed a manual review of a subset of the associations to validate how well MetaMap performed in identifying diagnoses mentioned in Medline citations that formed the basis of the Medline associations. The overlap of associations based on ICD-9 codes in the clinical and Medline datasets was low: only 6.6% of the 3.1 million associations found in the clinical dataset were also present in the Medline dataset. Further, a manual review of a subset of the associations that appeared in both datasets revealed that co-occurring diagnoses from Medline citations do not always represent clinically meaningful associations. Identifying novel associations derived from large clinical datasets remains challenging. Medline as a sole data source for existing knowledge may not be adequate to filter out widely known associations. In this study, novel associations were not readily identified. Further improvements in accuracy and relevance for tools such as MetaMap are needed to realize their expected utility. 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.

  17. Using rice genome-wide association studies to identify DNA markers for marker-assisted selection

    Science.gov (United States)

    Rice association mapping panels are collections of rice (Oryza sativa L.) accessions developed for genome-wide association (GWA) studies. One of these panels, the Rice Diversity Panel 1 (RDP1) was phenotyped by various research groups for several traits of interest, and more recently, genotyped with...

  18. Challenges to Academic Integrity: Identifying the Factors Associated with the Cheating Chain

    Science.gov (United States)

    Bernardi, Richard A.; Banzhoff, Caitlin A.; Martino, Abigail M.; Savasta, Katelyn J.

    2012-01-01

    This study examined whether seeing other students cheat in examinations and/or knowing students who routinely cheat in examinations associates with other students' cheating behaviour and on their intentions to cheat in the future. We also examined whether cheating in minor and/or major examinations associates with students' intentions to cheat in…

  19. Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

    NARCIS (Netherlands)

    Sud, A. (Amit); Thomsen, H. (Hauke); Law, P.J. (Philip J.); A. Försti (Asta); Filho, M.I.D.S. (Miguel Inacio Da Silva); Holroyd, A. (Amy); P. Broderick (Peter); Orlando, G. (Giulia); Lenive, O. (Oleg); Wright, L. (Lauren); R. Cooke (Rosie); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); J. Peto (Julian); F. Canzian (Federico); Eeles, R. (Rosalind); Z. Kote-Jarai; K.R. Muir (K.); Pashayan, N. (Nora); B.E. Henderson (Brian); C.A. Haiman (Christopher); S. Benlloch (Sara); F.R. Schumacher (Fredrick R); Olama, A.A.A. (Ali Amin Al); S.I. Berndt (Sonja); G. Conti (Giario); F. Wiklund (Fredrik); S.J. Chanock (Stephen); Stevens, V.L. (Victoria L.); C.M. Tangen (Catherine M.); Batra, J. (Jyotsna); Clements, J. (Judith); H. Grönberg (Henrik); Schleutker, J. (Johanna); D. Albanes (Demetrius); Weinstein, S. (Stephanie); K. Wolk (Kerstin); West, C. (Catharine); Mucci, L. (Lorelei); Cancel-Tassin, G. (Géraldine); Koutros, S. (Stella); Sorensen, K.D. (Karina Dalsgaard); L. Maehle; D. Neal (David); S.P.L. Travis (Simon); Hamilton, R.J. (Robert J.); S.A. Ingles (Sue); B.S. Rosenstein (Barry S.); Lu, Y.-J. (Yong-Jie); Giles, G.G. (Graham G.); A. Kibel (Adam); Vega, A. (Ana); M. Kogevinas (Manolis); Penney, K.L. (Kathryn L.); Park, J.Y. (Jong Y.); Stanford, J.L. (Janet L.); C. Cybulski (Cezary); B.G. Nordestgaard (Børge); Brenner, H. (Hermann); Maier, C. (Christiane); Kim, J. (Jeri); E.M. John (Esther); P.J. Teixeira; Neuhausen, S.L. (Susan L.); De Ruyck, K. (Kim); Razack, A. (Azad); Newcomb, L.F. (Lisa F.); Lessel, D. (Davor); Kaneva, R. (Radka); N. Usmani (Nawaid); F. Claessens; Townsend, P.A. (Paul A.); Dominguez, M.G. (Manuela Gago); Roobol, M.J. (Monique J.); F. Menegaux (Florence); P. Hoffmann (Per); M.M. Nöthen (Markus); K.-H. JöCkel (Karl-Heinz); Strandmann, E.P.V. (Elke Pogge Von); Lightfoot, T. (Tracy); Kane, E. (Eleanor); Roman, E. (Eve); Lake, A. (Annette); Montgomery, D. (Dorothy); Jarrett, R.F. (Ruth F.); A.J. Swerdlow (Anthony ); A. Engert (Andreas); N. Orr (Nick); K. Hemminki (Kari); Houlston, R.S. (Richard S.)

    2017-01-01

    textabstractSeveral susceptibility loci for classical Hodgkin lymphoma have been reported. However, much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies, a new genome-wide association study, and replication totalling 5,314 cases and

  20. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

    NARCIS (Netherlands)

    Wain, Louise V.; Verwoert, Germaine C.; O'Reilly, Paul F.; Shi, Gang; Johnson, Toby; Johnson, Andrew D.; Bochud, Murielle; Rice, Kenneth M.; Henneman, Peter; Smith, Albert V.; Ehret, Georg B.; Amin, Najaf; Larson, Martin G.; Mooser, Vincent; Hadley, David; Doerr, Marcus; Bis, Joshua C.; Aspelund, Thor; Esko, Tonu; Janssens, A. Cecile J. W.; Zhao, Jing Hua; Heath, Simon; Laan, Maris; Fu, Jingyuan; Pistis, Giorgio; Luan, Jian'an; Arora, Pankaj; Lucas, Gavin; Pirastu, Nicola; Pichler, Irene; Jackson, Anne U.; Webster, Rebecca J.; Zhang, Feng; Peden, John F.; Schmidt, Helena; Tanaka, Toshiko; Campbell, Harry; Igl, Wilmar; Milaneschi, Yuri; Hottenga, Jouke-Jan; Vitart, Veronique; Chasman, Daniel I.; Trompet, Stella; Bragg-Gresham, Jennifer L.; Alizadeh, Behrooz Z.; Chambers, John C.; Guo, Xiuqing; Lehtimaki, Terho; Kuehnel, Brigitte; Lopez, Lorna M.; Polasek, Ozren; Boban, Mladen; Nelson, Christopher P.; Morrison, Alanna C.; Pihur, Vasyl; Ganesh, Santhi K.; Hofman, Albert; Kundu, Suman; Mattace-Raso, Francesco U. S.; Rivadeneira, Fernando; Sijbrands, Eric J. G.; Uitterlinden, Andre G.; Hwang, Shih-Jen; Vasan, Ramachandran S.; Wang, Thomas J.; Bergmann, Sven; Vollenweider, Peter; Waeber, Gerard; Laitinen, Jaana; Pouta, Anneli; Zitting, Paavo; McArdle, Wendy L.; Kroemer, Heyo K.; Voelker, Uwe; Voelzke, Henry; Glazer, Nicole L.; Taylor, Kent D.; Harris, Tamara B.; Alavere, Helene; Haller, Toomas; Keis, Aime; Tammesoo, Mari-Liis; Aulchenko, Yurii; Barroso, Ines; Khaw, Kay-Tee; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Eyheramendy, Susana; Org, Elin; Sober, Siim; Lu, Xiaowen; Nolte, Ilja M.; Penninx, Brenda W.; Corre, Tanguy; Masciullo, Corrado; Sala, Cinzia; Groop, Leif; Voight, Benjamin F.; Melander, Olle; O'Donnell, Christopher J.; Salomaa, Veikko; d'Adamo, Adamo Pio; Fabretto, Antonella; Faletra, Flavio; Ulivi, Sheila; Del Greco, Fabiola M.; Facheris, Maurizio; Collins, Francis S.; Bergman, Richard N.; Beilby, John P.; Hung, Joseph; Musk, A. William; Mangino, Massimo; Shin, So-Youn; Soranzo, Nicole; Watkins, Hugh; Goel, Anuj; Hamsten, Anders; Gider, Pierre; Loitfelder, Marisa; Zeginigg, Marion; Hernandez, Dena; Najjar, Samer S.; Navarro, Pau; Wild, Sarah H.; Corsi, Anna Maria; Singleton, Andrew; de Geus, Eco J. C.; Willemsen, Gonneke; Parker, Alex N.; Rose, Lynda M.; Buckley, Brendan; Stott, David; Orru, Marco; Uda, Manuela; van der Klauw, Melanie M.; Zhang, Weihua; Li, Xinzhong; Scott, James; Chen, Yii-Der Ida; Burke, Gregory L.; Kahonen, Mika; Viikari, Jorma; Doering, Angela; Meitinger, Thomas; Davies, Gail; Starr, John M.; Emilsson, Valur; Plump, Andrew; Lindeman, Jan H.; 't Hoen, Peter A. C.; Koenig, Inke R.; Felix, Janine F.; Clarke, Robert; Hopewell, Jemma C.; Ongen, Halit; Breteler, Monique; Debette, Stephanie; DeStefano, Anita L.; Fornage, Myriam; Mitchell, Gary F.; Smith, Nicholas L.; Holm, Hilma; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Samani, Nilesh J.; Preuss, Michael; Rudan, Igor; Hayward, Caroline; Deary, Ian J.; Wichmann, H-Erich; Raitakari, Olli T.; Palmas, Walter; Kooner, Jaspal S.; Stolk, Ronald P.; Jukema, J. Wouter; Wright, Alan F.; Boomsma, Dorret I.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wilson, James F.; Ferrucci, Luigi; Schmidt, Reinhold; Farrall, Martin; Spector, Tim D.; Palmer, Lyle J.; Tuomilehto, Jaakko; Pfeufer, Arne; Gasparini, Paolo; Siscovick, David; Altshuler, David; Loos, Ruth J. F.; Toniolo, Daniela; Snieder, Harold; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J.; Oostra, Ben A.; Metspalu, Andres; Launer, Lenore; Rettig, Rainer; Strachan, David P.; Beckmann, Jacques S.; Witteman, Jacqueline C. M.; Erdmann, Jeanette; van Dijk, Ko Willems; Boerwinkle, Eric; Boehnke, Michael; Ridker, Paul M.; Jarvelin, Marjo-Riitta; Chakravarti, Aravinda; Abecasis, Goncalo R.; Gudnason, Vilmundur; Newton-Cheh, Christopher; Levy, Daniel; Munroe, Patricia B.; Psaty, Bruce M.; Caulfield, Mark J.; Rao, Dabeeru C.; Tobin, Martin D.; Elliott, Paul; van Duijn, Cornelia M.

    2011-01-01

    Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we

  1. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    NARCIS (Netherlands)

    Felix, Janine F.; Bradfield, Jonathan P.; Monnereau, Claire; van der Valk, Ralf J. P.; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Moller, Eskil; Mahajan, Anubha; Pitkanen, Niina; Joro, Raimo; Cavadino, Alana; Huikari, Ville; Franks, Steve; Groen-Blokhuis, Maria M.; Cousminer, Diana L.; Marsh, Julie A.; Lehtimaki, Terho; Curtin, John A.; Vioque, Jesus; Ahluwalia, Tarunveer S.; Myhre, Ronny; Price, Thomas S.; Vilor-Tejedor, Natalia; Yengo, Loic; Grarup, Niels; Ntalla, Ioanna; Ang, Wei; Atalay, Mustafa; Bisgaard, Hans; Blakemore, Alexandra I.; Bonnefond, Amelie; Carstensen, Lisbeth; Eriksson, Johan; Flexeder, Claudia; Franke, Lude; Geller, Frank; Geserick, Mandy; Hartikainen, Anna-Liisa; Haworth, Claire M. A.; Hirschhorn, Joel N.; Hofman, Albert; Holm, Jens-Christian; Horikoshi, Momoko; Hottenga, Jouke Jan; Huang, Jinyan; Kadarmideen, Haja N.; Kahonen, Mika; Kiess, Wieland; Lakka, Hanna-Maaria; Lakka, Timo A.; Lewin, Alexandra M.; Liang, Liming; Lyytikainen, Leo-Pekka; Ma, Baoshan; Magnus, Per; McCormack, Shana E.; McMahon, George; Mentch, Frank D.; Middeldorp, Christel M.; Murray, Clare S.; Pahkala, Katja; Pers, Tune H.; Pfaefle, Roland; Postma, Dirkje S.; Power, Christine; Simpson, Angela; Sengpiel, Verena; Tiesler, Carla M. T.; Torrent, Maties; Uitterlinden, Andre G.; van Meurs, Joyce B.; Vinding, Rebecca; Waage, Johannes; Wardle, Jane; Zeggini, Eleftheria; Zemel, Babette S.; Dedoussis, George V.; Pedersen, Oluf; Froguel, Philippe; Sunyer, Jordi; Plomin, Robert; Jacobsson, Bo; Hansen, Torben; Gonzalez, Juan R.; Custovic, Adnan; Raitakari, Olli T.; Pennell, Craig E.; Widen, Elisabeth; Boomsma, Dorret I.; Koppelman, Gerard H.; Sebert, Sylvain; Jarvelin, Marjo-Riitta; Hypponen, Elina; McCarthy, Mark I.; Lindi, Virpi; Harri, Niinikoski; Koerner, Antje; Bonnelykke, Klaus; Heinrich, Joachim; Melbye, Mads; Rivadeneira, Fernando; Hakonarson, Hakon; Ring, Susan M.; Smith, George Davey; Sorensen, Thorkild I. A.; Timpson, Nicholas J.; Grant, Struan F. A.; Jaddoe, Vincent W. V.

    2016-01-01

    A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex-and age-adjusted standard deviation scores. We

  2. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    NARCIS (Netherlands)

    J.F. Felix (Janine); J.P. Bradfield (Jonathan); C. Monnereau; R.J.P. van der Valk (Ralf); E. Stergiakouli (Evie); A. Chesi (Alessandra); R. Gaillard (Romy); B. Feenstra (Bjarke); E. Thiering (Elisabeth); E. Kreiner-Møller (Eskil); A. Mahajan (Anubha); Niina Pitkänen; R. Joro (Raimo); A. Cavadino (Alana); V. Huikari (Ville); S. Franks (Steve); M. Groen-Blokhuis (Maria); D.L. Cousminer (Diana); J.A. Marsh (Julie); T. Lehtimäki (Terho); J.A. Curtin (John); J. Vioque (Jesus); T.S. Ahluwalia (Tarunveer Singh); R. Myhre (Ronny); T.S. Price (Thomas); Natalia Vilor-Tejedor; L. Yengo (Loic); N. Grarup (Niels); I. Ntalla (Ioanna); W.Q. Ang (Wei); M. Atalay (Mustafa); H. Bisgaard (Hans); A.I.F. Blakemore (Alexandra); A. Bonnefond (Amélie); L. Carstensen (Lisbeth); J.G. Eriksson (Johan G.); C. Flexeder (Claudia); L. Franke (Lude); F. Geller (Frank); M. Geserick (Mandy); A.L. Hartikainen; C.M.A. Haworth (Claire M.); J.N. Hirschhorn (Joel N.); A. Hofman (Albert); J.-C. Holm (Jens-Christian); M. Horikoshi (Momoko); J.J. Hottenga (Jouke Jan); J. Huang (Jian); H.N. Kadarmideen (Haja N.); M. Kähönen (Mika); W. Kiess (Wieland); T.A. Lakka (Timo); T.A. Lakka (Timo); A. Lewin (Alex); L. Liang (Liming); L.-P. Lyytikäinen (Leo-Pekka); B. Ma (Baoshan); P. Magnus (Per); S.E. McCormack (Shana E.); G. Mcmahon (George); F.D. Mentch (Frank); C.M. Middeldorp (Christel); C.S. Murray (Clare S.); K. Pahkala (Katja); T.H. Pers (Tune); R. Pfäffle (Roland); D.S. Postma (Dirkje); C. Power (Christine); A. Simpson (Angela); V. Sengpiel (Verena); C. Tiesler (Carla); M. Torrent (Maties); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); R. Vinding (Rebecca); J. Waage (Johannes); J. Wardle (Jane); E. Zeggini (Eleftheria); B.S. Zemel (Babette S.); G.V. Dedoussis (George); O. Pedersen (Oluf); P. Froguel (Philippe); J. Sunyer (Jordi); R. Plomin (Robert); B. Jacobsson (Bo); T. Hansen (Torben); J.R. Gonzalez (Juan R.); A. Custovic; O.T. Raitakari (Olli T.); C.E. Pennell (Craig); Elisabeth Widén; D.I. Boomsma (Dorret); G.H. Koppelman (Gerard); S. Sebert (Sylvain); M.-R. Jarvelin (Marjo-Riitta); E. Hypponen (Elina); M.I. McCarthy (Mark); V. Lindi (Virpi); N. Harri (Niinikoski); A. Körner (Antje); K. Bønnelykke (Klaus); J. Heinrich (Joachim); M. Melbye (Mads); F. Rivadeneira Ramirez (Fernando); H. Hakonarson (Hakon); S.M. Ring (Susan); G.D. Smith; T.I.A. Sørensen (Thorkild I.A.); N.J. Timpson (Nicholas); S.F.A. Grant (Struan); V.W.V. Jaddoe (Vincent); H.J. Kalkwarf (Heidi J.); J.M. Lappe (Joan M.); V. Gilsanz (Vicente); S.E. Oberfield (Sharon E.); J.A. Shepherd (John A.); A. Kelly (Andrea)

    2016-01-01

    textabstractA large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation

  3. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

    NARCIS (Netherlands)

    H. Schunkert (Heribert); I.R. König (Inke); S. Kathiresan (Sekar); M.P. Reilly (Muredach); T.L. Assimes (Themistocles); H. Holm (Hilma); M. Preuss (Michael); A.F.R. Stewart (Alexandre); M. Barbalic (maja); C. Gieger (Christian); D. Absher (Devin); Z. Aherrahrou (Zouhair); H. Allayee (Hooman); D. Altshuler (David); S.S. Anand (Sonia); K.K. Andersen (Karl); J.L. Anderson (Jeffrey); D. Ardissino (Diego); S.G. Ball (Stephen); A.J. Balmforth (Anthony); T.A. Barnes (Timothy); D.M. Becker (Diane); K. Berger (Klaus); J.C. Bis (Joshua); S.M. Boekholdt (Matthijs); E.A. Boerwinkle (Eric); P.S. Braund (Peter); M.J. Brown (Morris); M.S. Burnett; I. Buysschaert (Ian); J.F. Carlquist (John); L. Chen (Li); S. Cichon (Sven); V. Codd (Veryan); R.W. Davies (Robert); G.V. Dedoussis (George); A. Dehghan (Abbas); S. Demissie (Serkalem); J. Devaney (Joseph); P. Diemert (Patrick); R. Do (Ron); A. Doering (Angela); S. Eifert (Sandra); N.E.E. Mokhtari; S.G. Ellis (Stephen); R. Elosua (Roberto); J.C. Engert (James); S.E. Epstein (Stephen); U. de Faire (Ulf); M. Fischer (Marcus); A.R. Folsom (Aaron); J. Freyer (Jennifer); B. Gigante (Bruna); D. Girelli (Domenico); S. Gretarsdottir (Solveig); V. Gudnason (Vilmundur); J.R. Gulcher (Jeffrey); E. Halperin (Eran); N. Hammond (Naomi); S.L. Hazen (Stanley); A. Hofman (Albert); B.D. Horne (Benjamin); T. Illig (Thomas); C. Iribarren (Carlos); G.T. Jones (Gregory); J.W. Jukema (Jan Wouter); M.A. Kaiser (Michael); R.C. Kaplan (Robert); K-T. Khaw (Kay-Tee); J.W. Knowles (Joshua); G. Kolovou (Genovefa); A. Kong (Augustine); R. Laaksonen (Reijo); D. Lambrechts (Diether); K. Leander (Karin); G. Lettre (Guillaume); X. Li (Xiaohui); W. Lieb (Wolfgang); C. Loley (Christina); A.J. Lotery (Andrew); P.M. Mannucci (Pier); S. Maouche (Seraya); N. Martinelli (Nicola); P.P. McKeown (Pascal); C. Meisinger (Christa); T. Meitinger (Thomas); O. Melander (Olle); P.A. Merlini; V. Mooser (Vincent); T. Morgan (Thomas); T.W. Mühleisen (Thomas); J.B. Muhlestein (Joseph); T. Münzel (Thomas); K. Musunuru (Kiran); J. Nahrstaedt (Janja); C.P. Nelson (Christopher P.); M.M. Nöthen (Markus); O. Olivieri (Oliviero); R.S. Patel (Riyaz); C.C. Patterson (Chris); A. Peters (Annette); F. Peyvandi (Flora); L. Qu (Liming); A.A. Quyyumi (Arshed); D.J. Rader (Daniel); L.S. Rallidis (Loukianos); C. Rice (Catherine); F.R. Rosendaal (Frits); D. Rubin (Diana); V. Salomaa (Veikko); M.L. Sampietro (Maria Lourdes); M.S. Sandhu (Manj); E.E. Schadt (Eric); A. Scḧsignfer (Arne); A. Schillert (Arne); S. Schreiber (Stefan); J. Schrezenmeir (Jürgen); S.M. Schwartz (Stephen); D.S. Siscovick (David); M. Sivananthan (Mohan); S. Sivapalaratnam (Suthesh); A.V. Smith (Albert Vernon); J.D. Snoep (Jaapjan); N. Soranzo (Nicole); J.A. Spertus (John); K. Stark (Klaus); K. Stirrups (Kathy); M. Stoll (Monika); W.H.W. Tang (Wilson); S. Tennstedt (Stephanie); G. Thorgeirsson (Gudmundur); G. Thorleifsson (Gudmar); M. Tomaszewski (Maciej); A.G. Uitterlinden (André); A.M. van Rij (Andre); B.F. Voight (Benjamin); N.J. Wareham (Nick); G.A. Wells (George); H.E. Wichmann (Heinz Erich); P.S. Wild (Philipp); C. Willenborg (Christina); J.C.M. Witteman (Jacqueline); B.J. Wright (Benjamin); S. Ye (Shu); T. Zeller (Tanja); A. Ziegler (Andreas); F. Cambien (François); A.H. Goodall (Alison); L.A. Cupples (Adrienne); T. Quertermous (Thomas); W. Mäsignrz (Winfried); C. Hengstenberg (Christian); S. Blankenberg (Stefan); W.H. Ouwehand (Willem); A.S. Hall (Alistair); J.J.P. Kastelein (John); P. Deloukas (Panagiotis); J.R. Thompson (John); K. Stefansson (Kari); R. Roberts (Robert); U. Thorsteinsdottir (Unnur); C.J. O'Donnell (Christopher); R. McPherson (Ruth); J. Erdmann (Jeanette); N.J. Samani (Nilesh)

    2011-01-01

    textabstractWe performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis

  4. Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility.

    Science.gov (United States)

    Knight, Jeffrey A; Skol, Andrew D; Shinde, Abhijit; Hastings, Darcie; Walgren, Richard A; Shao, Jin; Tennant, Thelma R; Banerjee, Mekhala; Allan, James M; Le Beau, Michelle M; Larson, Richard A; Graubert, Timothy A; Cox, Nancy J; Onel, Kenan

    2009-05-28

    Therapy-related acute myeloid leukemia (t-AML) is a rare but fatal complication of cytotoxic therapy. Whereas sporadic cancer results from interactions between complex exposures and low-penetrance alleles, t-AML results from an acute exposure to a limited number of potent genotoxins. Consequently, we hypothesized that the effect sizes of variants associated with t-AML would be greater than in sporadic cancer, and, therefore, that these variants could be detected even in a modest-sized cohort. To test this, we undertook an association study in 80 cases and 150 controls using Affymetrix Mapping 10K arrays. Even at nominal significance thresholds, we found a significant excess of associations over chance; for example, although 6 associations were expected at P less than .001, we found 15 (P(enrich) = .002). To replicate our findings, we genotyped the 10 most significantly associated single nucleotide polymorphisms (SNPs) in an independent t-AML cohort (n = 70) and obtained evidence of association with t-AML for 3 SNPs in the subset of patients with loss of chromosomes 5 or 7 or both, acquired abnormalities associated with prior exposure to alkylator chemotherapy. Thus, we conclude that the effect of genetic factors contributing to cancer risk is potentiated and more readily discernable in t-AML compared with sporadic cancer.

  5. Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Joshi, Amit D; Andersson, Charlotte; Buch, Stephan

    2016-01-01

    BACKGROUND & AIMS: A genome-wide association study (GWAS) of 280 cases identified the hepatic cholesterol transporter ABCG8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other GWAS of this phenotype. We performed a large-scale, meta-analysis o...

  6. A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation

    NARCIS (Netherlands)

    Bramon, Elvira; Pirinen, Matti; Strange, Amy; Lin, Kuang; Freeman, Colin; Bellenguez, Celine; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J.; Arranz, Maria J.; Bakker, Steven; Bender, Stephan; Bruggeman, Richard; Cahn, Wiepke; Chandler, David; Collier, David A.; Crespo-Facorro, Benedicto; Dazzan, Paola; de Haan, Lieuwe; di Forti, Marta; Dragovic, Milan; Giegling, Ina; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S.; Kalaydjieva, Luba; Kravariti, Eugenia; Lawrie, Stephen; Lins-Zen, Don H.; Mata, Ignacio; McDonald, Colm; McIntosh, Andrew; Myin-Germeys, Inez; Ophoff, Roel A.; Pariante, Carmine M.; Paunio, Tiina; Picchioni, Marco; Ripke, Stephan; Rujescu, Dan; Sauer, Heinrich; Shaikh, Madiha; Sussmann, Jessika; Suvisaari, Jaana; Tosato, Sarah; Toulopoulou, Timothea; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Whalley, Heather; Wiersma, Durk; Blackwell, Jenefer M.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A. Z.; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Wood, Nicholas W.; Barroso, Ines; Peltonen, Leena; Lewis, Cathryn M.; Murray, Robin M.; Donnelly, Peter; Powell, John; Spencer, Chris C. A.

    2014-01-01

    Background: Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. Methods: 1239 cases with schizophrenia, schizoaffective

  7. A genome-wide association analysis of a broad psychosis phenotype identifies three loci for further investigation

    NARCIS (Netherlands)

    Bramon, Elvira; Pirinen, Matti; Strange, Amy; Lin, Kuang; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J.; Arranz, Maria J.; Bakker, Steven; Bender, Stephan; Bruggeman, Richard; Cahn, Wiepke; Chandler, David; Collier, David A.; Crespo-Facorro, Benedicto; Dazzan, Paola; de Haan, Lieuwe; Di Forti, Marta; Dragović, Milan; Giegling, Ina; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, René S.; Kalaydjieva, Luba; Kravariti, Eugenia; Lawrie, Stephen; Linszen, Don H.; Mata, Ignacio; McDonald, Colm; McIntosh, Andrew; Myin-Germeys, Inez; Ophoff, Roel A.; Pariante, Carmine M.; Paunio, Tiina; Picchioni, Marco; Ripke, Stephan; Rujescu, Dan; Sauer, Heinrich; Shaikh, Madiha; Sussmann, Jessika; Suvisaari, Jaana; Tosato, Sarah; Toulopoulou, Timothea; van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Whalley, Heather; Wiersma, Durk; Blackwell, Jenefer M.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz A. Z.; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Wood, Nicholas W.; Barroso, Ines; Peltonen, Leena; Lewis, Cathryn M.; Murray, Robin M.; Donnelly, Peter; Powell, John; Spencer, Chris C. A.; Collier, David; van, Jim; Jankowski, Janusz; Viswanathan, Ananth C.; Hellenthal, Garrett; Giannoulatou, Eleni; Hunt, Sarah E.; Gwilliam, Rhian; Blackburn, Hannah; Gillman, Matthew; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; McCarthy, Mark I.

    2014-01-01

    Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. 1239 cases with schizophrenia, schizoaffective disorder, or psychotic

  8. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    NARCIS (Netherlands)

    Van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; Van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; Van Dijk, Freerk; Willemsen, Gonneke; De Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W J H; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; De Craen, Anton J M; Uh, Hae Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Cupples, L. Adrienne; Jukema, J. Wouter; Van Der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke Jan; Uitterlinden, Andre G.; Swertz, Morris A.; Van Ommen, Gert Jan B; De Bakker, Paul I W; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; Van Duijn, Cornelia M.; Neerincx, Pieter B T; Elbers, Clara C.; Palamara, Pier Francesco; Peer, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; Van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F J; Stoneking, Mark; De Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; Van Den Berg, Leonard H.; Byelas, Heorhiy; Den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Van Der Velde, K. Joeri; Van Setten, Jessica; Kattenberg, Mathijs; Van Schaik, Barbera D C; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; de Bakker, Paul I W

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel created

  9. Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies

    NARCIS (Netherlands)

    Joshi, A.D. (Amit D.); Andersson, C. (Charlotte); T. Buch (Thorsten); Stender, S. (Stefan); R. Noordam; L.-C. Weng; Weeke, P.E. (Peter E.); P. Auer (Paul); B.O. Boehm (Bernhard); C. Chen (Constance); Choi, H. (Hyon); Curhan, G. (Gary); J.C. Denny (Joshua C.); I. de Vivo (Immaculata); Eicher, J.D. (John D.); D. Ellinghaus (David); A.R. Folsom (Aaron); Fuchs, C. (Charles); Gala, M. (Manish); J. Haessler (Jeff); A. Hofman (Albert); Hu, F. (Frank); D. Hunter (David); H.L.A. Janssen (Harry); J.H. Kang; C. Kooperberg (Charles); P. Kraft (Peter); W. Kratzer (Wolfgang); W. Lieb (Wolfgang); P.L. Lutsey (Pamela); S. Darwish Murad (Sarwa); B.G. Nordestgaard (Børge); L.R. Pasquale (Louis); A. Reiner (Alexander); P.M. Ridker (Paul); E.B. Rimm (Eric B.); L.M. Rose (Lynda); Shaffer, C.M. (Christian M.); C. Schafmayer (Clemens); Tamimi, R.M. (Rulla M.); A.G. Uitterlinden (André); U. Völker (Uwe); H. Völzke (Henry); Wakabayashi, Y. (Yoshiyuki); J.L. Wiggs (Janey L.); Zhu, J. (Jun); Roden, D.M. (Dan M.); B.H.Ch. Stricker (Bruno); W. Tang (Weihong); A. Teumer (Alexander); J. Hampe (Jochen); A. Tybjaerg-Hansen; D.I. Chasman (Daniel); Chan, A.T. (Andrew T.); A.D. Johnson (Andrew)

    2016-01-01

    textabstractBackground & Aims A genome-wide association study (GWAS) of 280 cases identified the hepatic cholesterol transporter ABCG8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other GWAS of this phenotype. We performed a large-scale,

  10. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

    NARCIS (Netherlands)

    Nalls, Mike A.; Pankratz, Nathan; Lill, Christina M.; Do, Chuong B.; Hernandez, Dena G.; Saad, Mohamad; DeStefano, Anita L.; Kara, Eleanna; Bras, Jose; Sharma, Manu; Schulte, Claudia; Keller, Margaux F.; Arepalli, Sampath; Letson, Christopher; Edsall, Connor; Stefansson, Hreinn; Liu, Xinmin; Pliner, Hannah; Lee, Joseph H.; Cheng, Rong; Ikram, M. Arfan; Ioannidis, John P. A.; Hadjigeorgiou, Georgios M.; Bis, Joshua C.; Martinez, Maria; Perlmutter, Joel S.; Goate, Alison; Marder, Karen; Fiske, Brian; Sutherland, Margaret; Xiromerisiou, Georgia; Myers, Richard H.; Clark, Lorraine N.; Stefansson, Kari; Hardy, John A.; Heutink, Peter; Chen, Honglei; Wood, Nicholas W.; Houlden, Henry; Payami, Haydeh; Brice, Alexis; Scott, William K.; Gasser, Thomas; Bertram, Lars; Eriksson, Nicholas; Foroud, Tatiana; Singleton, Andrew B.; Plagnol, Vincent; Sheerin, Una-Marie; Simón-Sánchez, Javier; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Dong, Jing; Gardner, Michelle; Gibbs, J. Raphael; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Wurster, Isabel; Mätzler, Walter; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R.; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Stefánsson, Hreinn; Bettella, Francesco; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Factor, S.; Higgins, D.; Evans, S.; Shill, H.; Stacy, M.; Danielson, J.; Marlor, L.; Williamson, K.; Jankovic, J.; Hunter, C.; Simon, D.; Ryan, P.; Scollins, L.; Saunders-Pullman, R.; Boyar, K.; Costan-Toth, C.; Ohmann, E.; Sudarsky, L.; Joubert, C.; Friedman, J.; Chou, K.; Fernandez, H.; Lannon, M.; Galvez-Jimenez, N.; Podichetty, A.; Thompson, K.; Lewitt, P.; Deangelis, M.; O'Brien, C.; Seeberger, L.; Dingmann, C.; Judd, D.; Marder, K.; Fraser, J.; Harris, J.; Bertoni, J.; Peterson, C.; Rezak, M.; Medalle, G.; Chouinard, S.; Panisset, M.; Hall, J.; Poiffaut, H.; Calabrese, V.; Roberge, P.; Wojcieszek, J.; Belden, J.; Jennings, D.; Marek, K.; Mendick, S.; Reich, S.; Dunlop, B.; Jog, M.; Horn, C.; Uitti, R.; Turk, M.; Ajax, T.; Mannetter, J.; Sethi, K.; Carpenter, J.; Dill, B.; Hatch, L.; Ligon, K.; Narayan, S.; Blindauer, K.; Abou-Samra, K.; Petit, J.; Elmer, L.; Aiken, E.; Davis, K.; Schell, C.; Wilson, S.; Velickovic, M.; Koller, W.; Phipps, S.; Feigin, A.; Gordon, M.; Hamann, J.; Licari, E.; Marotta-Kollarus, M.; Shannon, B.; Winnick, R.; Simuni, T.; Videnovic, A.; Kaczmarek, A.; Williams, K.; Wolff, M.; Rao, J.; Cook, M.; Fernandez, M.; Kostyk, S.; Hubble, J.; Campbell, A.; Reider, C.; Seward, A.; Camicioli, R.; Carter, J.; Nutt, J.; Andrews, P.; Morehouse, S.; Stone, C.; Mendis, T.; Grimes, D.; Alcorn-Costa, C.; Gray, P.; Haas, K.; Vendette, J.; Sutton, J.; Hutchinson, B.; Young, J.; Rajput, A.; Klassen, L.; Shirley, T.; Manyam, B.; Simpson, P.; Whetteckey, J.; Wulbrecht, B.; Truong, D.; Pathak, M.; Frei, K.; Luong, N.; Tra, T.; Tran, A.; Vo, J.; Lang, A.; Kleiner- Fisman, G.; Nieves, A.; Johnston, L.; So, J.; Podskalny, G.; Giffin, L.; Atchison, P.; Allen, C.; Martin, W.; Wieler, M.; Suchowersky, O.; Furtado, S.; Klimek, M.; Hermanowicz, N.; Niswonger, S.; Shults, C.; Fontaine, D.; Aminoff, M.; Christine, C.; Diminno, M.; Hevezi, J.; Dalvi, A.; Kang, U.; Richman, J.; Uy, S.; Sahay, A.; Gartner, M.; Schwieterman, D.; Hall, D.; Leehey, M.; Culver, S.; Derian, T.; Demarcaida, T.; Thurlow, S.; Rodnitzky, R.; Dobson, J.; Lyons, K.; Pahwa, R.; Gales, T.; Thomas, S.; Shulman, L.; Weiner, W.; Dustin, K.; Singer, C.; Zelaya, L.; Tuite, P.; Hagen, V.; Rolandelli, S.; Schacherer, R.; Kosowicz, J.; Gordon, P.; Werner, J.; Serrano, C.; Roque, S.; Kurlan, R.; Berry, D.; Gardiner, I.; Hauser, R.; Sanchez-Ramos, J.; Zesiewicz, T.; Delgado, H.; Price, K.; Rodriguez, P.; Wolfrath, S.; Pfeiffer, R.; Davis, L.; Pfeiffer, B.; Dewey, R.; Hayward, B.; Johnson, A.; Meacham, M.; Estes, B.; Walker, F.; Hunt, V.; O'Neill, C.; Racette, B.; Swisher, L.; Dijamco, Cheri; Conley, Emily Drabant; Dorfman, Elizabeth; Tung, Joyce Y.; Hinds, David A.; Mountain, Joanna L.; Wojcicki, Anne; Lew, M.; Klein, C.; Golbe, L.; Growdon, J.; Wooten, G. F.; Watts, R.; Guttman, M.; Goldwurm, S.; Saint-Hilaire, M. H.; Baker, K.; Litvan, I.; Nicholson, G.; Nance, M.; Drasby, E.; Isaacson, S.; Burn, D.; Pramstaller, P.; Al-hinti, J.; Moller, A.; Sherman, S.; Roxburgh, R.; Slevin, J.; Perlmutter, J.; Mark, M. H.; Huggins, N.; Pezzoli, G.; Massood, T.; Itin, I.; Corbett, A.; Chinnery, P.; Ostergaard, K.; Snow, B.; Cambi, F.; Kay, D.; Samii, A.; Agarwal, P.; Roberts, J. W.; Higgins, D. S.; Molho, Eric; Rosen, Ami; Montimurro, J.; Martinez, E.; Griffith, A.; Kusel, V.; Yearout, D.; Zabetian, C.; Clark, L. N.; Liu, X.; Lee, J. H.; Taub, R. Cheng; Louis, E. D.; Cote, L. J.; Waters, C.; Ford, B.; Fahn, S.; Vance, Jeffery M.; Beecham, Gary W.; Martin, Eden R.; Nuytemans, Karen; Pericak-Vance, Margaret A.; Haines, Jonathan L.; DeStefano, Anita; Seshadri, Sudha; Choi, Seung Hoan; Frank, Samuel; Psaty, Bruce M.; Rice, Kenneth; Longstreth, W. T.; Ton, Thanh G. N.; Jain, Samay; van Duijn, Cornelia M.; Verlinden, Vincent J.; Koudstaal, Peter J.; Singleton, Andrew; Cookson, Mark; Hernandez, Dena; Nalls, Michael; Zonderman, Alan; Ferrucci, Luigi; Johnson, Robert; Longo, Dan; O'Brien, Richard; Traynor, Bryan; Troncoso, Juan; van der Brug, Marcel; Zielke, Ronald; Weale, Michael; Ramasamy, Adaikalavan; Dardiotis, Efthimios; Tsimourtou, Vana; Spanaki, Cleanthe; Plaitakis, Andreas; Bozi, Maria; Stefanis, Leonidas; Vassilatis, Dimitris; Koutsis, Georgios; Panas, Marios; Lunnon, Katie; Lupton, Michelle; Powell, John; Parkkinen, Laura; Ansorge, Olaf

    2014-01-01

    We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were

  11. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk.

    Science.gov (United States)

    Orr, Nick; Lemnrau, Alina; Cooke, Rosie; Fletcher, Olivia; Tomczyk, Katarzyna; Jones, Michael; Johnson, Nichola; Lord, Christopher J; Mitsopoulos, Costas; Zvelebil, Marketa; McDade, Simon S; Buck, Gemma; Blancher, Christine; Trainer, Alison H; James, Paul A; Bojesen, Stig E; Bokmand, Susanne; Nevanlinna, Heli; Mattson, Johanna; Friedman, Eitan; Laitman, Yael; Palli, Domenico; Masala, Giovanna; Zanna, Ines; Ottini, Laura; Giannini, Giuseppe; Hollestelle, Antoinette; Ouweland, Ans M W van den; Novaković, Srdjan; Krajc, Mateja; Gago-Dominguez, Manuela; Castelao, Jose Esteban; Olsson, Håkan; Hedenfalk, Ingrid; Easton, Douglas F; Pharoah, Paul D P; Dunning, Alison M; Bishop, D Timothy; Neuhausen, Susan L; Steele, Linda; Houlston, Richard S; Garcia-Closas, Montserrat; Ashworth, Alan; Swerdlow, Anthony J

    2012-11-01

    We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 × 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 × 10(-15); OR = 1.50).

  12. Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk

    DEFF Research Database (Denmark)

    Guo, Xingyi; Long, Jirong; Zeng, Chenjie

    2015-01-01

    BACKGROUND: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. METHODS: We conducted a fine-mapping analysis in 55,540 breast...... was associated with level of expression of TET2 in breast normal and tumor tissue. CONCLUSION: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. IMPACT: Fine-mapping...... study with large sample size warranted for identification of independent loci for breast cancer risk....

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

    DEFF Research Database (Denmark)

    Okbay, Aysu; Baselmans, Bart M L; De Neve, Jan-Emmanuel

    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...... 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 associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated...

  14. 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...

  15. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity

    DEFF Research Database (Denmark)

    Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana

    2016-01-01

    . First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip...... (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant...

  16. Genome-wide association studies identify 25 genetic loci associated with resistance to Bacterial Cold Water Disease in rainbow trout

    Science.gov (United States)

    Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonids aquaculture. In previous studies we have identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a high density SNP array and...

  17. Identifying the Manipulative Mating Methods Associated With Psychopathic Traits and BPD Features.

    Science.gov (United States)

    Muñoz Centifanti, Luna C; Thomson, Nicholas D; Kwok, Angela H

    2016-12-01

    Psychopathy and borderline personality disorder (BPD) traits are associated with coercion and manipulation within relationships. The authors investigated whether BPD traits were uniquely associated with manipulation for emotional closeness whereas psychopathy was used for the purpose of attaining physical closeness. A community sample (N = 164) reported on mating behaviors, psychopathic traits, and BPD traits. Hierarchical regressions were conducted to predict mating behaviors that would account for the overlap between psychopathy and BPD. Total psychopathic traits were associated with lower levels of relationship exclusivity, greater use of partner poaching, and perpetration of sexual coercion. Specifically, callousness and egocentricity were related to lower relationship exclusivity. BPD traits were associated with the use of mate retention strategies, mate poaching, and victimization in sexual coercion. These findings indicate that manipulative mating behaviors encompass tools to achieve sex and intimacy. Those with BPD traits use these tools for emotional closeness, whereas those with psychopathic traits use them to obtain physical closeness and gratification.

  18. Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis.

    Science.gov (United States)

    Toyo-Oka, L; Mahasirimongkol, S; Yanai, H; Mushiroda, T; Wattanapokayakit, S; Wichukchinda, N; Yamada, N; Smittipat, N; Juthayothin, T; Palittapongarnpim, P; Nedsuwan, S; Kantipong, P; Takahashi, A; Kubo, M; Sawanpanyalert, P; Tokunaga, K

    2017-09-01

    Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10 -4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10 -3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Molecular epidemiology identifies HIV transmission networks associated with younger age and heterosexual exposure among Korean individuals.

    Science.gov (United States)

    Chin, Bum Sik; Chaillon, Antoine; Mehta, Sanjay R; Wertheim, Joel O; Kim, Gayeon; Shin, Hyoung-Shik; Smith, Davey M

    2016-10-01

    To evaluate if HIV transmission networks could be elucidated from data collected in a short time frame, 131 HIV-1 pol sequences were analyzed which were generated from treatment-naïve Korean individuals who were sequentially identified over 1 year. A transmission linkage was inferred when there was a genetic distance network, which demonstrated that molecular epidemiology with currently generated data (i.e., drug resistance genotypes) can be used to identify local transmission networks, even over a short timeframe. J. Med. Virol. 88:1832-1835, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS

    NARCIS (Netherlands)

    Smith, Bradley N.; Ticozzi, Nicola; Fallini, Claudia; Gkazi, Athina Soragia; Topp, Simon; Kenna, Kevin P.; Scotter, Emma L.; Kost, Jason; Keagle, Pamela; Miller, Jack W.; Calini, Daniela; Vance, Caroline; Danielson, Eric W.; Troakes, Claire; Tiloca, Cinzia; Al-Sarraj, Safa; Lewis, Elizabeth A.; King, Andrew; Colombrita, Claudia; Pensato, Viviana; Castellotti, Barbara; de Belleroche, Jacqueline; Baas, Frank; ten Asbroek, Anneloor L. M. A.; Sapp, Peter C.; McKenna-Yasek, Diane; McLaughlin, Russell L.; Polak, Meraida; Asress, Seneshaw; Esteban-Pérez, Jesús; Muñoz-Blanco, José Luis; Simpson, Michael; van Rheenen, Wouter; Diekstra, Frank P.; Lauria, Giuseppe; Duga, Stefano; Corti, Stefania; Cereda, Cristina; Corrado, Lucia; Sorarù, Gianni; Morrison, Karen E.; Williams, Kelly L.; Nicholson, Garth A.; Blair, Ian P.; Dion, Patrick A.; Leblond, Claire S.; Rouleau, Guy A.; Hardiman, Orla; Veldink, Jan H.; van den Berg, Leonard H.; Al-Chalabi, Ammar; Pall, Hardev; Shaw, Pamela J.; Turner, Martin R.; Talbot, Kevin; Taroni, Franco; García-Redondo, Alberto; Wu, Zheyang; Glass, Jonathan D.; Gellera, Cinzia; Ratti, Antonia; Brown, Robert H.; Silani, Vincenzo; Shaw, Christopher E.; Landers, John E.; D'alfonso, Sandra; Mazzini, Letizia; Comi, Giacomo P.; del Bo, Roberto; Ceroni, Mauro; Gagliardi, Stella; Querin, Giorgia; Bertolin, Cinzia

    2014-01-01

    Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an

  1. Identifying and evaluating environmental impacts associated with timber harvest scheduling policies.

    Science.gov (United States)

    Robert M. Randall; Robert W. Sassaman

    1979-01-01

    Expected impacts on the ecosystem and nontimber benefits (that is, people's use of the resources—recreation, hunting, fishing, swimming, etc.) resulting from alternative timber harvest scheduling policies are identified and evaluated for the Mount Hood National Forest. Environmental criteria are established and used in evaluations of timber harvest and...

  2. Difficulty Identifying Feelings, Distress Tolerance and Compulsive Buying: Analyzing the Associations to Inform Therapeutic Strategies

    Science.gov (United States)

    Rose, Paul; Segrist, Daniel J.

    2012-01-01

    Difficulty identifying feelings (a component of alexithymia) and distress tolerance both appear to play a role in impulse-control problems. The goal of the present study was to build upon past research by developing a model of the relations between these constructs and compulsive buying. Participants from the United States and Canada completed a…

  3. Identifying temporal and causal contributions of neural processes underlying the Implicit Association Test (IAT

    Directory of Open Access Journals (Sweden)

    Chad Edward Forbes

    2012-11-01

    Full Text Available The Implicit Association Test (IAT is a popular behavioral measure that assesses the associative strength between outgroup members and stereotypical and counterstereotypical traits. Less is known, however, about the degree to which the IAT reflects automatic processing. Two studies examined automatic processing contributions to a gender-IAT using a data driven, social neuroscience approach. Performance on congruent (e.g., categorizing male names with synonyms of strength and incongruent (e.g., categorizing female names with synonyms of strength IAT blocks were separately analyzed using EEG (event-related potentials, or ERPs, and coherence; Study 1 and lesion (Study 2 methodologies. Compared to incongruent blocks, performance on congruent IAT blocks was associated with more positive ERPs that manifested in frontal and occipital regions at automatic processing speeds, occipital regions at more controlled processing speeds and was compromised by volume loss in the anterior temporal lobe, insula and medial PFC. Performance on incongruent blocks was associated with volume loss in supplementary motor areas, cingulate gyrus and a region in medial PFC similar to that found for congruent blocks. Greater coherence was found between frontal and occipital regions to the extent individuals exhibited more bias. This suggests there are separable neural contributions to congruent and incongruent blocks of the IAT but there is also a surprising amount of overlap. Given the temporal and regional neural distinctions, these results provide converging evidence that stereotypic associative strength assessed by the IAT indexes automatic processing to a degree.

  4. Association Study Identifying a New Susceptibility Gene (AUTS2 for Schizophrenia

    Directory of Open Access Journals (Sweden)

    Bao Zhang

    2014-10-01

    Full Text Available Schizophrenia (SCZ is a severe and debilitating mental disorder, and the specific genetic factors that underlie the risk for SCZ remain elusive. The autism susceptibility candidate 2 (AUTS2 gene has been reported to be associated with autism, suicide, alcohol consumption, and heroin dependence. We hypothesized that AUTS2 might be associated with SCZ. In the present study, three polymorphisms (rs6943555, rs7459368, and rs9886351 in the AUTS2 gene were genotyped in 410 patients with SCZ and 435 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and forced PCR-RFLP methods. We detected an association between SCZ and the rs6943555 genotype distribution (odds ratio (OR = 1.363, 95% confidence interval (CI: 0.848–2.191, p = 0.001. The association remained significant after adjusting for gender, and a significant effect (p = 0.001 was observed among the females. In the present study, rs6943555 was determined to be associated with female SCZ. Our results confirm previous reports which have suggested that rs6943555 might elucidate the pathogenesis of schizophrenia and play an important role in its etiology.

  5. Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape

    Czech Academy of Sciences Publication Activity Database

    Cole, J.B.; Manyama, M.; Kimwaga, E.; Mathayo, J.; Larson, J.R.; Liberton, D.K.; Lukowiak, K.; Ferrara, T.M.; Riccardi, S.L.; Li, M.; Mio, W.; Procházková, Michaela; Williams, T.; Li, H.; Jones, K. L.; Klein, O. D.; Santorico, S.A.; Hallgrimsson, B.; Spritz, R.A.

    2016-01-01

    Roč. 12, č. 8 (2016), č. článku e1006174. ISSN 1553-7404 Institutional support: RVO:68378050 Keywords : cause char-syndrome * wide association * phosphodiesterase 8a * heritability * recognition * mutations * allometry * variants * parents Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.100, year: 2016

  6. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium

    NARCIS (Netherlands)

    Johnatty, S.E.; Tyrer, J.P.; Kar, S.; Beesley, J.; Lu, Y.; Gao, B.; Fasching, P.A.; Hein, A.; Ekici, A.B.; Beckmann, M.W.; Lambrechts, D.; Nieuwenhuysen, E. Van; Vergote, I.; Lambrechts, S.; Rossing, M.A.; Doherty, J.A.; Chang-Claude, J.; Modugno, F.; Ness, R.B.; Moysich, K.B.; Levine, D.A.; Kiemeney, L.A.L.M.; Massuger, L.F.A.G.; Gronwald, J.; Lubinski, J.; Jakubowska, A.; Cybulski, C.; Brinton, L.; Lissowska, J.; Wentzensen, N.; Song, H.; Rhenius, V.; Campbell, I.; Eccles, D.; Sieh, W.; Whittemore, A.S.; McGuire, V.; Rothstein, J.H.; Sutphen, R.; Anton-Culver, H.; Ziogas, A.; Gayther, S.A.; Gentry-Maharaj, A.; Menon, U.; Ramus, S.J.; Pearce, C.L.; Pike, M.C.; Stram, D.O.; Wu, A.H.; Kupryjanczyk, J.; Dansonka-Mieszkowska, A.; Rzepecka, I.K.; Spiewankiewicz, B.; Goodman, M.T.; Wilkens, L.R.; Carney, M.E.; Thompson, P.J.; Heitz, F.; Bois, A. du; Schwaab, I.; Harter, P.; Pisterer, J.; Hillemanns, P.; Karlan, B.Y.; Walsh, C.; Lester, J.; Orsulic, S.; Winham, S.J.; Earp, M.; Larson, M.C.; Fogarty, Z.C.; Hogdall, E.; Jensen, A.; Kjaer, S.K.; Fridley, B.L.; Cunningham, J.M.; Vierkant, R.A.; Schildkraut, J.M.; Iversen, E.S.; Terry, K.L.; Cramer, D.W; Bandera, E.V.; Orlow, I.; Pejovic, T.; Bean, Y.; Hogdall, C.; Lundvall, L.; McNeish, I.; Paul, J.; Carty, K.; Siddiqui, N.; Glasspool, R.; Sellers, T.; Kennedy, C.; Chiew, Y.E.; Berchuck, A.; MacGregor, S.; Pharoah, P.D.; Goode, E.L.; Defazio, A.; et al.,

    2015-01-01

    PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for

  7. An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

    Directory of Open Access Journals (Sweden)

    Iksoo Huh

    Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

  8. [Identifying different susceptibility loci associated with early onset diabetes and cardiovascular disease in Mexican families].

    Science.gov (United States)

    Canizales-Quinteros, Samuel; Huertas-Vázquez, Adriana; Riba-Ramírez, Laura; Monroy-Guzmán, Adriana; Domínguez-López, Aarón; Romero-Hidalgo, Sandra; Aguilar-Salinas, Carlos; Rodríguez-Torres, Maribel; Ramírez-Jiménez, Salvador; Tusié-Luna, María Teresa

    2005-01-01

    Coronary artery disease and diabetes mellitus are among the primary mortality and morbidity causes in Mexico. Genetic factors play a fundamental role in the development of these entities. In the past few years due to the recognition and study of families with monogenic forms of diabetes and dislipidemias associated with development of atherosclerosis, several genes and loci have been associated with these conditions through genetic linkage studies. These studies have provided evidence of the genetic heterogeneity that exists and the type of genes involved in different ethnic groups. The study of Mexican families with early-onset diabetes and combined familial hyperlipidemia showed the participation of different genetic loci associated with these conditions in the Mexican population. These findings show the value of gene mapping strategies in the identification of the genetic component in these entities in our population.

  9. Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures.

    Directory of Open Access Journals (Sweden)

    Yin-Ping Zhang

    Full Text Available Hip OF carries the highest morbidity and mortality. Previous studies revealed that individual genes/loci in the Tumor Necrosis Factor (TNF-Related Apoptosis-Inducing Ligand (TRAIL pathway were associated with bone metabolism. This study aims to verify the potential association between hip OF and TRAIL pathway.Using genome-wide genotype data from Affymetrix 500 K SNP arrays, we performed novel pathway-based association analyses for hip OF in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls.The TRAIL pathway achieved a significant p value (p = 0.01 for association with hip OF. Among the 38 genes in the TRAIL pathway, seven genes achieved nominally significant association with hip OF (p<0.05; the TNFSF10 (TRAIL gene obtained the most significant p value (p = 1.70×10(-4. SNPs (rs719126, rs6533015, rs9594738, rs1805034, rs11160706 from five genes (CFLAR, NFKB1, TNFSF11, TNFRSF11A, TRAF3 of the pathway had minor alleles that appear to be protective to hip OF. SNPs (rs6445063 and rs4259415 from two genes (TNFSF10 and TNFRSF10B of the pathway had minor alleles (A that are associated with an increased risk of hip OF, with the ORs (odds ratios of 16.51 (95%CI:3.83-71.24 and 1.37 (95%CI:1.08-1.74, respectively.Our study supports the potential role of the TRAIL pathway in the pathogenesis of hip OF in Chinese Han population. Further functional study of this pathway will be pursued to determine the mechanism by which it confers risk to hip OF.

  10. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    OpenAIRE

    Felix, Janine; Bradfield, Jonathan; Monnereau, C.; Valk, Ralf; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Møller, Eskil; Mahajan, Anubha; Niina Pitkänen; Joro, Raimo; Cavadino, Alana; Huikari, Ville

    2016-01-01

    textabstractA large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5...

  11. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci

    Science.gov (United States)

    Melum, Espen; Franke, Andre; Schramm, Christoph; Weismüller, Tobias J; Gotthardt, Daniel Nils; Offner, Felix A; Juran, Brian D; Laerdahl, Jon K; Labi, Verena; Björnsson, Einar; Weersma, Rinse K; Henckaerts, Liesbet; Teufel, Andreas; Rust, Christian; Ellinghaus, Eva; Balschun, Tobias; Boberg, Kirsten Muri; Ellinghaus, David; Bergquist, Annika; Sauer, Peter; Ryu, Euijung; Hov, Johannes Roksund; Wedemeyer, Jochen; Lindkvist, Björn; Wittig, Michael; Porte, Robert J; Holm, Kristian; Gieger, Christian; Wichmann, H-Erich; Stokkers, Pieter; Ponsioen, Cyriel Y; Runz, Heiko; Stiehl, Adolf; Wijmenga, Cisca; Sterneck, Martina; Vermeire, Severine; Beuers, Ulrich; Villunger, Andreas; Schrumpf, Erik; Lazaridis, Konstantinos N; Manns, Michael P; Schreiber, Stefan; Karlsen, Tom H

    2015-01-01

    Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4–7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10−16 and P = 4.1 × 10−8, respectively). PMID:21151127

  12. A genome-wide association meta-analysis identifies new childhood obesity loci

    Science.gov (United States)

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, André; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M.A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St. Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeinera, Fernando; Uitterlinden, André G.; van Duijn, Cornelia M.; van der Valk, Ralf J.P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, William J.; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Mägi, Reedik; Boreham, Colin A.G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimäki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George; Ring, Susan M.; Kemp, John P.; Buxton, Jessica L.; Blakemore, Alexandra I.F.; Bustamante, Mariona; Guxens, Mònica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Møller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Inês; O'Rahilly, Stephen; Meirhaeghe, Aline; Sørensen, Thorkild I.A.; Power, Chris; Palmer, Lyle J.; Hinney, Anke; Widen, Elisabeth; Farooqi, I. Sadaf; McCarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo-Riitta; Jaddoe, Vincent W.V.; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI1. PMID:22484627

  13. Handwashing, sanitation and family planning practices are the strongest underlying determinants of child stunting in rural indigenous communities of Jharkhand and Odisha, Eastern India: a cross-sectional study.

    Science.gov (United States)

    Saxton, Jennifer; Rath, Shibanand; Nair, Nirmala; Gope, Rajkumar; Mahapatra, Rajendra; Tripathy, Prasanta; Prost, Audrey

    2016-10-01

    The World Health Organisation has called for global action to reduce child stunting by 40% by 2025. One third of the world's stunted children live in India, and children belonging to rural indigenous communities are the worst affected. We sought to identify the strongest determinants of stunting among indigenous children in rural Jharkhand and Odisha, India, to highlight key areas for intervention. We analysed data from 1227 children aged 6-23.99 months and their mothers, collected in 2010 from 18 clusters of villages with a high proportion of people from indigenous groups in three districts. We measured height and weight of mothers and children, and captured data on various basic, underlying and immediate determinants of undernutrition. We used Generalised Estimating Equations to identify individual determinants associated with children's height-for-age z-score (HAZ; p family planning, reducing diarrhoeal infections, improving handwashing practices, increasing access to income and strengthening health and sanitation infrastructure. © 2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.

  14. Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3.

    Directory of Open Access Journals (Sweden)

    Sara Lindstrom

    2011-02-01

    Full Text Available Genome-wide association studies (GWAS have identified multiple single nucleotide polymorphisms (SNPs associated with prostate cancer risk. However, whether these associations can be consistently replicated, vary with disease aggressiveness (tumor stage and grade and/or interact with non-genetic potential risk factors or other SNPs is unknown. We therefore genotyped 39 SNPs from regions identified by several prostate cancer GWAS in 10,501 prostate cancer cases and 10,831 controls from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3. We replicated 36 out of 39 SNPs (P-values ranging from 0.01 to 10⁻²⁸. Two SNPs located near KLK3 associated with PSA levels showed differential association with Gleason grade (rs2735839, P = 0.0001 and rs266849, P = 0.0004; case-only test, where the alleles associated with decreasing PSA levels were inversely associated with low-grade (as defined by Gleason grade < 8 tumors but positively associated with high-grade tumors. No other SNP showed differential associations according to disease stage or grade. We observed no effect modification by SNP for association with age at diagnosis, family history of prostate cancer, diabetes, BMI, height, smoking or alcohol intake. Moreover, we found no evidence of pair-wise SNP-SNP interactions. While these SNPs represent new independent risk factors for prostate cancer, we saw little evidence for effect modification by other SNPs or by the environmental factors examined.

  15. Identifying nontechnical skills associated with safety in the emergency department: a scoping review of the literature.

    Science.gov (United States)

    Flowerdew, Lynsey; Brown, Ruth; Vincent, Charles; Woloshynowych, Maria

    2012-05-01

    Understanding the nontechnical skills specifically applicable to the emergency department (ED) is essential to facilitate training and more broadly consider interventions to reduce error. The aim of this scoping review is to first identify and then explore in depth the nontechnical skills linked to safety in the ED. The review was conducted in 2 stages. In stage 1, online databases were searched for published empirical studies linking nontechnical skills to safety and performance in the ED. Articles were analyzed to identify key ED nontechnical skills. In stage 2, these key skills were used to generate additional key words, which enabled a second search of the literature to be undertaken and expand on the evidence available for review. In stage 1, 11 articles were retrieved for data analysis and 9 core emergency medicine nontechnical skills were identified. These were communicating, managing workload, anticipating, situational awareness, supervising and providing feedback, leadership, maintaining standards, using assertiveness, and decisionmaking. In stage 2, a secondary search, using these 9 skills and related terms, uncovered a further 21 relevant articles. Therefore, 32 articles were used to describe the main nontechnical skills linked to safety in the ED. This article highlights the challenges of reviewing a topic for which the terms are not clearly defined in the literature. A novel methodological approach is described that provides a structured and transparent process for reviewing the literature in emerging areas of interest. A series of literature reviews focusing on individual nontechnical skills will provide a clearer understanding of how the skills identified contribute to safety in the ED. Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

  16. Identifying a Major QTL Associated with Salinity Tolerance in Nile Tilapia Using QTL-Seq.

    Science.gov (United States)

    Gu, Xiao Hui; Jiang, Dan Li; Huang, Yan; Li, Bi Jun; Chen, Chao Hao; Lin, Hao Ran; Xia, Jun Hong

    2018-02-01

    Selection of new lines with high salinity tolerance allows for economically feasible production of tilapias in brackish water areas. Mapping QTLs and identifying the markers linked to salinity-tolerant traits are the first steps in the improvement of the tolerance in tilapia through marker-assisted selection techniques. By using QTL-seq strategy and linkage-based analysis, two significant QTL intervals (chrLG4 and chrLG18) on salinity-tolerant traits were firstly identified in the Nile tilapia. Fine mapping with microsatellite and SNP markers suggested a major QTL region that located at 23.0 Mb of chrLG18 and explained 79% of phenotypic variation with a LOD value of 95. Expression analysis indicated that at least 10 genes (e.g., LACTB2, KINH, NCOA2, DIP2C, LARP4B, PEX5R, and KCNJ9) near or within the QTL interval were significantly differentially expressed in intestines, brains, or gills under 10, 15, or 20 ppt challenges. Our findings suggest that QTL-seq can be effectively utilized in QTL mapping of salinity-tolerant traits in fish. The identified major QTL is a promising locus to improve our knowledge on the genetic mechanism of salinity tolerance in tilapia.

  17. Identifying the Factors Influencing Professional Volunteer Leadership in the National Association of Extension 4-H Agents

    Science.gov (United States)

    Lamm, Alexa; Nistler, Debbie; Stedman, Nicole

    2012-01-01

    Many Extension professional associations have had trouble getting members to participate in national leadership opportunities. The study reported here examined the perception of members of a national Extension professional organization (NAE4-HA) regarding specific leadership actions. It found the single act of taking on a leadership position…

  18. Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease

    NARCIS (Netherlands)

    Khor, Chiea Chuen; Davila, Sonia; Breunis, Willemijn B.; Lee, Yi-Ching; Shimizu, Chisato; Wright, Victoria J.; Yeung, Rae S. M.; Tan, Dennis E. K.; Sim, Kar Seng; Wang, Jie Jin; Wong, Tien Yin; Pang, Junxiong; Mitchell, Paul; Cimaz, Rolando; Dahdah, Nagib; Cheung, Yiu-Fai; Huang, Guo-Ying; Yang, Wanling; Park, In-Sook; Lee, Jong-Keuk; Wu, Jer-Yuarn; Levin, Michael; Burns, Jane C.; Burgner, David; Kuijpers, Taco W.; Hibberd, Martin L.; Lau, Yu-Lung; Zhang, Jing; Ma, Xiao-Jing; Liu, Fang; Wu, Lin; Yoo, Jeong-Jin; Hong, Soo-Jong; Kim, Kwi-Joo; Kim, Jae-Jung; Park, Young-Mi; Mi Hong, Young; Sohn, Sejung; Young Jang, Gi; Ha, Kee-Soo; Nam, Hyo-Kyoung; Byeon, Jung-Hye; Weon Yun, Sin; Ki Han, Myung; Lee, Kyung-Yil; Hwang, Ja-Young; Rhim, Jung-Woo; Seob Song, Min; Lee, Hyoung-Doo; Kim, Dong Soo; Lee, Jae-Moo; Chang, Jeng-Sheng; Tsai, Fuu-Jen; Liang, Chi-Di; Chen, Ming-Ren; Chi, Hsin; Chiu, Nan-Chang; Huang, Fu-Yuan; Chang, Luan-Yin; Huang, Li-Min; Kuo, Ho-Chang; Huang, Kao-Pin; Lee, Meng-Luen; Hwang, Betau; Huang, Yhu-Chering; Lee, Pi-Chang; Odam, Miranda; Christiansen, Frank T.; Witt, Campbell; Goldwater, Paul; Curtis, Nigel; Palasanthiran, Pamela; Ziegler, John; Nissen, Michael; Nourse, Clare; Kuipers, Irene M.; Ottenkamp, Jaap J.; Geissler, Judy; Biezeveld, Maarten; Tacke, Carline; Filippini, Luc; Brogan, Paul; Klein, Nigel; Shah, Vanita; Dillon, Michael; Booy, Robert; Shingadia, Delane; Bose, Anu; Mukasa, Thomas; Tulloh, Robert; Michie, Colin; Newburger, Jane W.; Baker, Annette L.; Rowley, Anne H.; Shulman, Stanford T.; Mason, Wilbert; Takahashi, Masato; Melish, Marian E.; Tremoulet, Adriana H.; Viswanathan, Ananth; Rochtchina, Elena; Attia, John; Scott, Rodney; Holliday, Elizabeth; Harrap, Stephen

    2011-01-01

    Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from

  19. Genome-wide association study identifies new prostate cancer susceptibility loci

    DEFF Research Database (Denmark)

    Schumacher, Fredrick R.; Berndt, Sonja I.; Siddiq, Afshan

    2011-01-01

    Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have iden...

  20. Genome-wide association analysis identifies 13 new risk loci for schizophrenia

    NARCIS (Netherlands)

    Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L.; Kähler, Anna K.; Akterin, Susanne; Bergen, Sarah E.; Collins, Ann L.; Crowley, James J.; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik K. E.; Sanchez, Nick; Stahl, Eli A.; Williams, Stephanie; Wray, Naomi R.; Xia, Kai; Bettella, Francesco; Borglum, Anders D.; Bulik-Sullivan, Brendan K.; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L.; Holmans, Peter; Hougaard, David M.; Kendler, Kenneth S.; Lin, Kuang; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Neale, Benjamin M.; O'Neill, Francis A.; Owen, Michael J.; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L.; Riley, Brien P.; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B.; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T.; Levinson, Douglas F.; Gejman, Pablo V.; Laurent, Claudine; Mowry, Bryan J.; O'Donovan, Michael C.; Pulver, Ann E.; Schwab, Sibylle G.; Wildenauer, Dieter B.; Dudbridge, Frank; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F. Bernard; Liang, Kung-Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A.; Nestadt, Gerald; Norton, Nadine; Papadimitriou, George N.; Ribble, Robert; Sanders, Alan R.; Silverman, Jeremy M.; Walsh, Dermot; Williams, Nigel M.; Wormley, Brandon; Arranz, Maria J.; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S.; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M.; Linszen, Don H.; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M.; Ophoff, Roel A.; van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden P.; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C. A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D.; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J.; Weston, Paul; Widaa, Sara; Whittaker, Pamela; McCarthy, Mark I.; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A.; Sklar, Pamela; Hultman, Christina M.; Sullivan, Patrick F.

    2013-01-01

    Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with

  1. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    NARCIS (Netherlands)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Pol, Hilleke E Hulshoff; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously

  2. Identifying Nonacademic Behaviors Associated with Post-School Employment and Education

    Science.gov (United States)

    McConnell, Amber E.; Martin, James E.; Juan, Chen Ya; Hennessey, Maeghan N.; Terry, Robert A.; el-Kazimi, Nidal A.; Pannells, Tammy C.; Willis, Donna M.

    2013-01-01

    We conducted an analysis of the secondary transition qualitative and quantitative research literature to build comprehensive constructs and lists of student nonacademic behaviors associated with post-high school employment and education. From a pool of 83 initial quantitative and qualitative studies, 35 met the inclusion criteria, and the analysis…

  3. A retrospective chart review to identify perinatal factors associated with food allergies

    Science.gov (United States)

    2012-01-01

    Background Gut flora are important immunomodulators that may be disrupted in individuals with atopic conditions. Probiotic bacteria have been suggested as therapeutic modalities to mitigate or prevent food allergic manifestations. We wished to investigate whether perinatal factors known to disrupt gut flora increase the risk of IgE-mediated food allergies. Methods Birth records obtained from 192 healthy children and 99 children diagnosed with food allergies were reviewed retrospectively. Data pertaining to delivery method, perinatal antibiotic exposure, neonatal nursery environment, and maternal variables were recorded. Logistic regression analysis was used to assess the association between variables of interest and subsequent food allergy diagnosis. Results Retrospective investigation did not find perinatal antibiotics, NICU admission, or cesarean section to be associated with increased risk of food allergy diagnosis. However, associations between food allergy diagnosis and male gender (66 vs. 33; p=0.02) were apparent in this cohort. Additionally, increasing maternal age at delivery was significantly associated with food allergy diagnosis during childhood (OR, 1.05; 95% CI, 1.017 to 1.105; p=0.005). Conclusions Gut flora are potent immunomodulators, but their overall contribution to immune maturation remains to be elucidated. Additional understanding of the interplay between immunologic, genetic, and environmental factors underlying food allergy development need to be clarified before probiotic therapeutic interventions can routinely be recommended for prevention or mitigation of food allergies. Such interventions may be well-suited in male infants and in infants born to older mothers. PMID:23078601

  4. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment

    NARCIS (Netherlands)

    Rietveld, Cornelius A; Medland, Sarah E; Derringer, Jaime; Yang, Jian; Esko, Tõnu; Martin, Nicolas W; Westra, Harm-Jan; Shakhbazov, Konstantin; Abdellaoui, Abdel; Agrawal, Arpana; Albrecht, Eva; Alizadeh, Behrooz Z; Amin, Najaf; Barnard, John; Baumeister, Sebastian E; Benke, Kelly S; Bielak, Lawrence F; Boatman, Jeffrey A; Boyle, Patricia A; Davies, Gail; de Leeuw, Christiaan; Eklund, Niina; Evans, Daniel S; Fehrmann, Rudolf; Fischer, Krista; Gieger, Christian; Gjessing, Håkon K; Hägg, Sara; Harris, Jennifer R; Hayward, Caroline; Holzapfel, Christina; Ibrahim-Verbaas, Carla A; Ingelsson, Erik; Jacobsson, Bo; Joshi, Peter K; Jugessur, Astanand; Kaakinen, Marika; Kanoni, Stavroula; Karjalainen, Juha; Kolcic, Ivana; Kristiansson, Kati; Kutalik, Zoltán; Lahti, Jari; Lee, Sang H; Lin, Peng; Lind, Penelope A; Liu, Yongmei; Lohman, Kurt; Loitfelder, Marisa; McMahon, George; Vidal, Pedro Marques; Meirelles, Osorio; Milani, Lili; Myhre, Ronny; Nuotio, Marja-Liisa; Oldmeadow, Christopher J; Petrovic, Katja E; Peyrot, Wouter J; Polasek, Ozren; Quaye, Lydia; Reinmaa, Eva; Rice, John P; Rizzi, Thais S; Schmidt, Helena; Schmidt, Reinhold; Smith, Albert V.; Smith, Jennifer A; Tanaka, Toshiko; Terracciano, Antonio; van der Loos, Matthijs J H M; Vitart, Veronique; Völzke, Henry; Wellmann, Jürgen; Yu, Lei; Zhao, Wei; Allik, Jüri; Attia, John R; Bandinelli, Stefania; Bastardot, François; Beauchamp, Jonathan; Bennett, David A; Berger, Klaus; Bierut, Laura J; Boomsma, Dorret I; Bültmann, Ute; Campbell, Harry; Chabris, Christopher F; Cherkas, Lynn; Chung, Mina K; Cucca, Francesco; de Andrade, Mariza; De Jager, Philip L; De Neve, Jan-Emmanuel; Deary, Ian J; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Eiríksdóttir, Guðny; Elderson, Martin F; Eriksson, Johan G; Evans, David M; Faul, Jessica D; Ferrucci, Luigi; Garcia, Melissa E; Grönberg, Henrik; Guðnason, Vilmundur; Hall, Per; Harris, Juliette M; Harris, Tamara B; Hastie, Nicholas D; Heath, Andrew C; Hernandez, Dena G; Hoffmann, Wolfgang; Hofman, Adriaan; Holle, Rolf; Holliday, Elizabeth G; Hottenga, Jouke-Jan; Iacono, William G; Illig, Thomas; Järvelin, Marjo-Riitta; Kähönen, Mika; Kaprio, Jaakko; Kirkpatrick, Robert M; Kowgier, Matthew; Latvala, Antti; Launer, Lenore J; Lawlor, Debbie A; Lehtimäki, Terho; Li, Jingmei; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C; Madden, Pamela A; Magnusson, Patrik K E; Mäkinen, Tomi E; Masala, Marco; McGue, Matt; Metspalu, Andres; Mielck, Andreas; Miller, Michael B; Montgomery, Grant W; Mukherjee, Sutapa; Nyholt, Dale R; Oostra, Ben A; Palmer, Lyle J; Palotie, Aarno; Penninx, Brenda W J H; Perola, Markus; Peyser, Patricia A; Preisig, Martin; Räikkönen, Katri; Raitakari, Olli T; Realo, Anu; Ring, Susan M; Ripatti, Samuli; Rivadeneira, Fernando; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sarin, Antti-Pekka; Schlessinger, David; Scott, Rodney J; Snieder, Harold; St Pourcain, Beate; Starr, John M; Sul, Jae Hoon; Surakka, Ida; Svento, Rauli; Teumer, Alexander; Tiemeier, Henning; van Rooij, Frank J A; Van Wagoner, David R; Vartiainen, Erkki; Viikari, Jorma; Vollenweider, Peter; Vonk, Judith M; Waeber, Gérard; Weir, David R; Wichmann, H-Erich; Widen, Elisabeth; Willemsen, Gonneke; Wilson, James F; Wright, Alan F; Conley, Dalton; Davey-Smith, George; Franke, Lude; Groenen, Patrick J F; Hofman, Albert; Johannesson, Magnus; Kardia, Sharon L R; Krueger, Robert F; Laibson, David; Martin, Nicholas G; Meyer, Michelle N; Posthuma, Danielle; Thurik, A Roy; Timpson, Nicholas J; Uitterlinden, André G; van Duijn, Cornelia M; Visscher, Peter M; Benjamin, Daniel J; Cesarini, David; Koellinger, Philipp D; Fehrmann, Rudolf

    2013-01-01

    A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three

  5. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.

    Science.gov (United States)

    Felix, Janine F; Bradfield, Jonathan P; Monnereau, Claire; van der Valk, Ralf J P; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Møller, Eskil; Mahajan, Anubha; Pitkänen, Niina; Joro, Raimo; Cavadino, Alana; Huikari, Ville; Franks, Steve; Groen-Blokhuis, Maria M; Cousminer, Diana L; Marsh, Julie A; Lehtimäki, Terho; Curtin, John A; Vioque, Jesus; Ahluwalia, Tarunveer S; Myhre, Ronny; Price, Thomas S; Vilor-Tejedor, Natalia; Yengo, Loïc; Grarup, Niels; Ntalla, Ioanna; Ang, Wei; Atalay, Mustafa; Bisgaard, Hans; Blakemore, Alexandra I; Bonnefond, Amelie; Carstensen, Lisbeth; Eriksson, Johan; Flexeder, Claudia; Franke, Lude; Geller, Frank; Geserick, Mandy; Hartikainen, Anna-Liisa; Haworth, Claire M A; Hirschhorn, Joel N; Hofman, Albert; Holm, Jens-Christian; Horikoshi, Momoko; Hottenga, Jouke Jan; Huang, Jinyan; Kadarmideen, Haja N; Kähönen, Mika; Kiess, Wieland; Lakka, Hanna-Maaria; Lakka, Timo A; Lewin, Alexandra M; Liang, Liming; Lyytikäinen, Leo-Pekka; Ma, Baoshan; Magnus, Per; McCormack, Shana E; McMahon, George; Mentch, Frank D; Middeldorp, Christel M; Murray, Clare S; Pahkala, Katja; Pers, Tune H; Pfäffle, Roland; Postma, Dirkje S; Power, Christine; Simpson, Angela; Sengpiel, Verena; Tiesler, Carla M T; Torrent, Maties; Uitterlinden, André G; van Meurs, Joyce B; Vinding, Rebecca; Waage, Johannes; Wardle, Jane; Zeggini, Eleftheria; Zemel, Babette S; Dedoussis, George V; Pedersen, Oluf; Froguel, Philippe; Sunyer, Jordi; Plomin, Robert; Jacobsson, Bo; Hansen, Torben; Gonzalez, Juan R; Custovic, Adnan; Raitakari, Olli T; Pennell, Craig E; Widén, Elisabeth; Boomsma, Dorret I; Koppelman, Gerard H; Sebert, Sylvain; Järvelin, Marjo-Riitta; Hyppönen, Elina; McCarthy, Mark I; Lindi, Virpi; Harri, Niinikoski; Körner, Antje; Bønnelykke, Klaus; Heinrich, Joachim; Melbye, Mads; Rivadeneira, Fernando; Hakonarson, Hakon; Ring, Susan M; Smith, George Davey; Sørensen, Thorkild I A; Timpson, Nicholas J; Grant, Struan F A; Jaddoe, Vincent W V

    2016-01-15

    A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. A retrospective chart review to identify perinatal factors associated with food allergies

    Directory of Open Access Journals (Sweden)

    Karpa Kelly

    2012-10-01

    Full Text Available Abstract Background Gut flora are important immunomodulators that may be disrupted in individuals with atopic conditions. Probiotic bacteria have been suggested as therapeutic modalities to mitigate or prevent food allergic manifestations. We wished to investigate whether perinatal factors known to disrupt gut flora increase the risk of IgE-mediated food allergies. Methods Birth records obtained from 192 healthy children and 99 children diagnosed with food allergies were reviewed retrospectively. Data pertaining to delivery method, perinatal antibiotic exposure, neonatal nursery environment, and maternal variables were recorded. Logistic regression analysis was used to assess the association between variables of interest and subsequent food allergy diagnosis. Results Retrospective investigation did not find perinatal antibiotics, NICU admission, or cesarean section to be associated with increased risk of food allergy diagnosis. However, associations between food allergy diagnosis and male gender (66 vs. 33; p=0.02 were apparent in this cohort. Additionally, increasing maternal age at delivery was significantly associated with food allergy diagnosis during childhood (OR, 1.05; 95% CI, 1.017 to 1.105; p=0.005. Conclusions Gut flora are potent immunomodulators, but their overall contribution to immune maturation remains to be elucidated. Additional understanding of the interplay between immunologic, genetic, and environmental factors underlying food allergy development need to be clarified before probiotic therapeutic interventions can routinely be recommended for prevention or mitigation of food allergies. Such interventions may be well-suited in male infants and in infants born to older mothers.

  7. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes

    DEFF Research Database (Denmark)

    Johnatty, Sharon E; Tyrer, Jonathan P; Kar, Siddhartha

    2015-01-01

    PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for ...

  8. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    DEFF Research Database (Denmark)

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  9. Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Matheson, Melanie C; Pers, Tune Hannes

    2013-01-01

    Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up th...

  10. A genome-wide association meta-analysis identifies new childhood obesity loci

    NARCIS (Netherlands)

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, Andre; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M. A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.; van der Valk, Ralf J. P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, W. James; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Magi, Reedik; Boreham, Colin A. G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimaki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George; Ring, Susan M.; Kemp, John P.; Buxton, Jessica L.; Blakemore, Alexandra I. F.; Bustamante, Mariona; Guxens, Monica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Moller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Ines; O'Rahilly, Stephen; Meirhaeghe, Aline; Sorensen, Thorkild I. A.; Power, Chris; Palmer, Lyle J.; Hinney, Anke; Widen, Elisabeth; Farooqi, I. Sadaf; McCarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo-Riitta; Jaddoe, Vincent W. V.; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F. A.

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of

  11. A genome-wide association meta-analysis identifies new childhood obesity loci

    NARCIS (Netherlands)

    Bradfield, J.P.; Taal, H.R.; Timpson, N.J.; Scherag, A.; Lecoeur, C.; Warrington, N.M.; Hypponen, E.; Holst, C.; Valcarcel, B.; Thiering, E.; Salem, R.M.; Schumacher, F.R.; Cousminer, D.L.; Sleiman, P.M.A.; Zhao, J.; Berkowitz, R.I.; Vimaleswaran, K.S.; Jarick, I.; Pennell, C.E.; Evans, D.M.; St Pourcain, B.; Berry, D.J.; Mook-Kanamori, D.O.; Hofman, A.; Rivadeneira, F.; Uitterlinden, A.G.; van Duijn, C.M.; van der Valk, R.J.P.; de Jongste, J.C.; Postma, D.S.; Boomsma, D.I.; Gauderman, W.J.; Hassanein, M.T.; Lindgren, C.M.; Mägi, R.; Boreham, C.A.G.; Neville, C.E.; Moreno, L.A.; Elliott, P.; Pouta, A.; Hartikainen, A.-L.; Li, M.; Raitakari, O.; Lehtimäki, T.; Eriksson, J.G.; Palotie, A.; Dallongeville, J.; Das, S.; Deloukas, P.; McMahon, G.; Ring, S.M.; Kemp, J.P.; Buxton, J.L.; Blakemore, A.I.F.; Bustamante, M.; Guxens, M.; Hirschhorn, J.N.; Gillman, M.W.; Kreiner-Møller, E.; Bisgaard, H.; Gilliland, F.D.; Heinrich, J.; Wheeler, E.; Barroso, I.; O'Rahilly, S.; Meirhaeghe, A.; Sørensen, T.I.A.; Power, C.; Palmer, L.J.; Hinney, A.; Widen, E.; Farooqi, I.S.; McCarthy, M.I.; Froguel, P.; Meyre, D.; Hebebrand, J.; Järvelin, M.J.; Jaddoe, V.W.V.; Smith, G.D.; Hakonarson, H.; Grant, S.F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of

  12. A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

    International Nuclear Information System (INIS)

    Mirabello, Lisa; Grotmol, Tom; Douglass, Chester; Hayes, Richard B; Hoover, Robert N; Savage, Sharon A; Yu, Kai; Berndt, Sonja I; Burdett, Laurie; Wang, Zhaoming; Chowdhury, Salma; Teshome, Kedest; Uzoka, Arinze; Hutchinson, Amy

    2011-01-01

    Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways. We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI). Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene FANCM (ORs 1.9-2.0, P = 0.003-0.004) and 2 SNPs downstream of the growth hormone gene GH1 (OR 1.6, P = 0.002; OR 0.5, P = 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: MDM2, MPG, FGF2, FGFR3, GNRH2, and IGF1. Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings

  13. Phase II Examination of Principal's Perceptions in Identifying Instructional Stages Associated with Teacher Output.

    Science.gov (United States)

    DeMoulin, Donald F.; Guyton, John

    Research previous to this study suggested that the efficiency of teachers increases to a zenith and from there decreases to a degree of inefficiency. This research led to a hypothesis that teaching characteristics can be associated with career development stages. In phase I of this study (conducted in 1983) 145 principals from 2 midwestern states…

  14. A genome-wide association meta-analysis identifies new childhood obesity loci

    DEFF Research Database (Denmark)

    Bradfield, Jonathan P; Taal, H Rob; Timpson, Nicholas J

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta...

  15. A retrospective chart review to identify perinatal factors associated with food allergies.

    Science.gov (United States)

    Dowhower Karpa, Kelly; Paul, Ian M; Leckie, J Alexander; Shung, Sharon; Carkaci-Salli, Nurgul; Vrana, Kent E; Mauger, David; Fausnight, Tracy; Poger, Jennifer

    2012-10-19

    Gut flora are important immunomodulators that may be disrupted in individuals with atopic conditions. Probiotic bacteria have been suggested as therapeutic modalities to mitigate or prevent food allergic manifestations. We wished to investigate whether perinatal factors known to disrupt gut flora increase the risk of IgE-mediated food allergies. Birth records obtained from 192 healthy children and 99 children diagnosed with food allergies were reviewed retrospectively. Data pertaining to delivery method, perinatal antibiotic exposure, neonatal nursery environment, and maternal variables were recorded. Logistic regression analysis was used to assess the association between variables of interest and subsequent food allergy diagnosis. Retrospective investigation did not find perinatal antibiotics, NICU admission, or cesarean section to be associated with increased risk of food allergy diagnosis. However, associations between food allergy diagnosis and male gender (66 vs. 33; p=0.02) were apparent in this cohort. Additionally, increasing maternal age at delivery was significantly associated with food allergy diagnosis during childhood (OR, 1.05; 95% CI, 1.017 to 1.105; p=0.005). Gut flora are potent immunomodulators, but their overall contribution to immune maturation remains to be elucidated. Additional understanding of the interplay between immunologic, genetic, and environmental factors underlying food allergy development need to be clarified before probiotic therapeutic interventions can routinely be recommended for prevention or mitigation of food allergies. Such interventions may be well-suited in male infants and in infants born to older mothers.

  16. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

    DEFF Research Database (Denmark)

    Horikoshi, Momoko; Yaghootkar, Hanieh; Mook-Kanamori, Dennis O

    2013-01-01

    -wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between...... diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome......Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2...

  17. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

    OpenAIRE

    Springelkamp, Henriët; Mishra, Aniket; Hysi, Pirro G.; Gharahkhani, Puya; Höhn, René; Khor, Chiea-Chuen; Cooke Bailey, Jessica N.; Luo, Xiaoyan; Ramdas, Wishal D.; Vithana, Eranga; Koh, Victor; Yazar, Seyhan; Xu, Liang; Forward, Hannah; Kearns, Lisa S.

    2015-01-01

    Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asia...

  18. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

    NARCIS (Netherlands)

    Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; den Heijer, Martin; Dieplinger, Benjamin; Ding, Jingzhong; Doerr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R.; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O'Connell, Jeff; O'Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Campbell, Harry; Boerwinkle, Eric; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Muenzel, Thomas; Newman, Anne B.; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Voelker, Uwe; Wright, Alan F.; Wichmann, H. -Erich; Wilson, James F.; Witteman, Jacqueline C. M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian; Dorr, M.; Munzel, T.; Volker, U.

    Background-Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

  19. GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment

    Science.gov (United States)

    Rietveld, Cornelius A.; Medland, Sarah E.; Derringer, Jaime; Yang, Jian; Esko, Tõnu; Martin, Nicolas W.; Westra, Harm-Jan; Shakhbazov, Konstantin; Abdellaoui, Abdel; Agrawal, Arpana; Albrecht, Eva; Alizadeh, Behrooz Z.; Amin, Najaf; Barnard, John; Baumeister, Sebastian E.; Benke, Kelly S.; Bielak, Lawrence F.; Boatman, Jeffrey A.; Boyle, Patricia A.; Davies, Gail; de Leeuw, Christiaan; Eklund, Niina; Evans, Daniel S.; Ferhmann, Rudolf; Fischer, Krista; Gieger, Christian; Gjessing, Håkon K.; Hägg, Sara; Harris, Jennifer R.; Hayward, Caroline; Holzapfel, Christina; Ibrahim-Verbaas, Carla A.; Ingelsson, Erik; Jacobsson, Bo; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika; Kanoni, Stavroula; Karjalainen, Juha; Kolcic, Ivana; Kristiansson, Kati; Kutalik, Zoltán; Lahti, Jari; Lee, Sang H.; Lin, Peng; Lind, Penelope A.; Liu, Yongmei; Lohman, Kurt; Loitfelder, Marisa; McMahon, George; Vidal, Pedro Marques; Meirelles, Osorio; Milani, Lili; Myhre, Ronny; Nuotio, Marja-Liisa; Oldmeadow, Christopher J.; Petrovic, Katja E.; Peyrot, Wouter J.; Polašek, Ozren; Quaye, Lydia; Reinmaa, Eva; Rice, John P.; Rizzi, Thais S.; Schmidt, Helena; Schmidt, Reinhold; Smith, Albert V.; Smith, Jennifer A.; Tanaka, Toshiko; Terracciano, Antonio; van der Loos, Matthijs J.H.M.; Vitart, Veronique; Völzke, Henry; Wellmann, Jürgen; Yu, Lei; Zhao, Wei; Allik, Jüri; Attia, John R.; Bandinelli, Stefania; Bastardot, François; Beauchamp, Jonathan; Bennett, David A.; Berger, Klaus; Bierut, Laura J.; Boomsma, Dorret I.; Bültmann, Ute; Campbell, Harry; Chabris, Christopher F.; Cherkas, Lynn; Chung, Mina K.; Cucca, Francesco; de Andrade, Mariza; De Jager, Philip L.; De Neve, Jan-Emmanuel; Deary, Ian J.; Dedoussis, George V.; Deloukas, Panos; Dimitriou, Maria; Eiriksdottir, Gudny; Elderson, Martin F.; Eriksson, Johan G.; Evans, David M.; Faul, Jessica D.; Ferrucci, Luigi; Garcia, Melissa E.; Grönberg, Henrik; Gudnason, Vilmundur; Hall, Per; Harris, Juliette M.; Harris, Tamara B.; Hastie, Nicholas D.; Heath, Andrew C.; Hernandez, Dena G.; Hoffmann, Wolfgang; Hofman, Adriaan; Holle, Rolf; Holliday, Elizabeth G.; Hottenga, Jouke-Jan; Iacono, William G.; Illig, Thomas; Järvelin, Marjo-Riitta; Kähönen, Mika; Kaprio, Jaakko; Kirkpatrick, Robert M.; Kowgier, Matthew; Latvala, Antti; Launer, Lenore J.; Lawlor, Debbie A.; Lehtimäki, Terho; Li, Jingmei; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C.; Madden, Pamela A.; Magnusson, Patrik K. E.; Mäkinen, Tomi E.; Masala, Marco; McGue, Matt; Metspalu, Andres; Mielck, Andreas; Miller, Michael B.; Montgomery, Grant W.; Mukherjee, Sutapa; Nyholt, Dale R.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Penninx, Brenda; Perola, Markus; Peyser, Patricia A.; Preisig, Martin; Räikkönen, Katri; Raitakari, Olli T.; Realo, Anu; Ring, Susan M.; Ripatti, Samuli; Rivadeneira, Fernando; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sarin, Antti-Pekka; Schlessinger, David; Scott, Rodney J.; Snieder, Harold; Pourcain, Beate St; Starr, John M.; Sul, Jae Hoon; Surakka, Ida; Svento, Rauli; Teumer, Alexander; Tiemeier, Henning; Rooij, Frank JAan; Van Wagoner, David R.; Vartiainen, Erkki; Viikari, Jorma; Vollenweider, Peter; Vonk, Judith M.; Waeber, Gérard; Weir, David R.; Wichmann, H.-Erich; Widen, Elisabeth; Willemsen, Gonneke; Wilson, James F.; Wright, Alan F.; Conley, Dalton; Davey-Smith, George; Franke, Lude; Groenen, Patrick J. F.; Hofman, Albert; Johannesson, Magnus; Kardia, Sharon L.R.; Krueger, Robert F.; Laibson, David; Martin, Nicholas G.; Meyer, Michelle N.; Posthuma, Danielle; Thurik, A. Roy; Timpson, Nicholas J.; Uitterlinden, André G.; van Duijn, Cornelia M.; Visscher, Peter M.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.

    2013-01-01

    A genome-wide association study of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent SNPs are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (R2 ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈ 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics. PMID:23722424

  20. First Identified Case in Literature: Association of Achalasia and Celiac Diseases

    Directory of Open Access Journals (Sweden)

    Ibrahim Bucak

    2014-12-01

    Full Text Available Celiac disease has been shown to cause problems related to gastrointestinal system motility such as reduction of the esophageal sphincter pressure and prolongation of gastric emptying time. Achalasia disease is a motor disorder that is charac¬terized by the absence of esophageal peristalsis and by incomplete relaxation of the lower esophageal sphincter. Association of achalasia and celiac diseases has not been reported yet. Our patient with growth and developmental retardation had vomiting effects which lasted for 3 years. Celiac disease was diagnosed serologically and histopathologically in our patient; we determined achalasia disease with esophagoscopic examination, upper gastrointestinal system contrast study, and esophageal manometer. Esophageal balloon dilatation was applied. This case is presented because of the interesting association between celiac disease and achalasia disease.

  1. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    DEFF Research Database (Denmark)

    Felix, Janine F; Bradfield, Jonathan P; Monnereau, Claire

    2016-01-01

    .011, P-value=3.12 x 10(-10)) increase in childhood body mass index in a population of 1,955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci......A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We...... included 35,668 children from 20 studies in the discovery phase and 11,873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide-significance (P-value

  2. Rapid whole-genome sequencing identifies a novel GABRA1 variant associated with West syndrome.

    Science.gov (United States)

    Farnaes, Lauge; Nahas, Shareef A; Chowdhury, Shimul; Nelson, James; Batalov, Serge; Dimmock, David M; Kingsmore, Stephen F

    2017-09-01

    A 9-mo-old infant was admitted with infantile spasms that improved on administration of topiramate and steroids. He also had developmental delay, esotropia, and hypsarrhythmia on interictal electroencephalogram (EEG), and normal brain magnetic resonance imaging (MRI). West syndrome is the triad of infantile spasms, interictal hypsarrhythmia, and mental retardation. Rapid trio whole-genome sequencing (WGS) revealed a novel, likely pathogenic, de novo variant in the gene encoding γ-aminobutyric acid (GABA) type A receptor, α1 polypeptide ( GABRA1 c.789G>A, p.Met263Ile) in the proband. GABRA1 mutations have been associated with early infantile epileptic encephalopathy type 19 (EIEE19). We suggest that GABRA1 p.Met263Ile is associated with a distinct West syndrome phenotype. © 2017 Farnaes et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Distinct ECG Phenotypes Identified in Hypertrophic Cardiomyopathy Using Machine Learning Associate With Arrhythmic Risk Markers

    Directory of Open Access Journals (Sweden)

    Aurore Lyon

    2018-03-01

    Full Text Available Aims: Ventricular arrhythmia triggers sudden cardiac death (SCD in hypertrophic cardiomyopathy (HCM, yet electrophysiological biomarkers are not used for risk stratification. Our aim was to identify distinct HCM phenotypes based on ECG computational analysis, and characterize differences in clinical risk factors and anatomical differences using cardiac magnetic resonance (CMR imaging.Methods: High-fidelity 12-lead Holter ECGs from 85 HCM patients and 38 healthy volunteers were analyzed using mathematical modeling and computational clustering to identify phenotypic subgroups. Clinical features and the extent and distribution of hypertrophy assessed by CMR were evaluated in the subgroups.Results: QRS morphology alone was crucial to identify three HCM phenotypes with very distinct QRS patterns. Group 1 (n = 44 showed normal QRS morphology, Group 2 (n = 19 showed short R and deep S waves in V4, and Group 3 (n = 22 exhibited short R and long S waves in V4-6, and left QRS axis deviation. However, no differences in arrhythmic risk or distribution of hypertrophy were observed between these groups. Including T wave biomarkers in the clustering, four HCM phenotypes were identified: Group 1A (n = 20, with primary repolarization abnormalities showing normal QRS yet inverted T waves, Group 1B (n = 24, with normal QRS morphology and upright T waves, and Group 2 and Group 3 remaining as before, with upright T waves. Group 1A patients, with normal QRS and inverted T wave, showed increased HCM Risk-SCD scores (1A: 4.0%, 1B: 1.8%, 2: 2.1%, 3: 2.5%, p = 0.0001, and a predominance of coexisting septal and apical hypertrophy (p < 0.0001. HCM patients in Groups 2 and 3 exhibited predominantly septal hypertrophy (85 and 90%, respectively.Conclusion: HCM patients were classified in four subgroups with distinct ECG features. Patients with primary T wave inversion not secondary to QRS abnormalities had increased HCM Risk-SCD scores and coexisting septal and apical

  4. Identifying and Reducing Health Risks Associated with Open-Air Burn Pits

    Science.gov (United States)

    2013-04-01

    Middle States Association of Colleges and Schools , 3624 Market Street, Philadelphia, PA 19104, (215) 662-5606. The Commission on Higher Education is an... Schools , 3624 Market Street, Philadelphia, PA 19104, (215) 662-5606. The Commission on Higher Education is an institutional accrediting agency...issued two canteens , whereas, upon arriving in Iraq in 2004, I was shown the location of containers full of pallets filled with 1.5 liter plastic

  5. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    NARCIS (Netherlands)

    C.E. Elks (Cathy); J.R.B. Perry (John); P. Sulem (Patrick); D.I. Chasman (Daniel); N. Franceschini (Nora); C. He (Chunyan); K.L. Lunetta (Kathryn); J.A. Visser (Jenny); E.M. Byrne (Enda); D.L. Cousminer (Diana); D.F. Gudbjartsson (Daniel); T. Esko (Tõnu); B. Feenstra (Bjarke); J.J. Hottenga (Jouke Jan); D.L. Koller (Daniel); Z. Kutalik (Zoltán); P. Lin (Peng); M. Mangino (Massimo); M. Marongiu (Mara); P.F. McArdle (Patrick); A.V. Smith (Albert Vernon); L. Stolk (Lisette); S. van Wingerden (Sophie); J.H. Zhao (Jing Hua); E. Albrecht (Eva); T. Corre (Tanguy); E. Ingelsson (Erik); C. Hayward (Caroline); P.K. Magnusson (Patrik); S. Ulivi (Shelia); N.M. Warrington (Nicole); L. Zgaga (Lina); H. Alavere (Helene); N. Amin (Najaf); T. Aspelund (Thor); S. Bandinelli (Stefania); I.E. Barroso (Inês); G. Berenson (Gerald); S.M. Bergmann (Sven); H. Blackburn (Hannah); E.A. Boerwinkle (Eric); J.E. Buring (Julie); F. Busonero; H. Campbell (Harry); S.J. Chanock (Stephen); W. Chen (Wei); M. Cornelis (Marilyn); D.J. Couper (David); A.D. Coviello (Andrea); P. d' Adamo (Pio); U. de Faire (Ulf); E.J.C. de Geus (Eco); P. Deloukas (Panagiotis); A. Döring (Angela); D.F. Easton (Douglas); G. Eiriksdottir (Gudny); V. Emilsson (Valur); J.G. Eriksson (Johan); L. Ferrucci (Luigi); A.R. Folsom (Aaron); T. Foroud (Tatiana); M. Garcia (Melissa); P. Gasparini (Paolo); F. Geller (Frank); C. Gieger (Christian); V. Gudnason (Vilmundur); A.S. Hall (Alistair); S.E. Hankinson (Susan); L. Ferreli (Liana); A.C. Heath (Andrew); D.G. Hernandez (Dena); A. Hofman (Albert); F.B. Hu (Frank); T. Illig (Thomas); M.R. Järvelin; A.D. Johnson (Andrew); D. Karasik (David); K-T. Khaw (Kay-Tee); D.P. Kiel (Douglas); T.O. Kilpelänen (Tuomas); I. Kolcic (Ivana); P. Kraft (Peter); L.J. Launer (Lenore); J.S.E. Laven (Joop); S. Li (Shengxu); J. Liu (Jianjun); D. Levy (Daniel); N.G. Martin (Nicholas); M. Melbye (Mads); V. Mooser (Vincent); J.C. Murray (Jeffrey); M.A. Nalls (Michael); P. Navarro (Pau); M. Nelis (Mari); A.R. Ness (Andrew); K. Northstone (Kate); B.A. Oostra (Ben); M. Peacock (Munro); C. Palmer (Cameron); A. Palotie (Aarno); G. Paré (Guillaume); A.N. Parker (Alex); N.L. Pedersen (Nancy); L. Peltonen (Leena Johanna); C.E. Pennell (Craig); P.D.P. Pharoah (Paul); O. Polasek (Ozren); A.S. Plump (Andrew); A. Pouta (Anneli); E. Porcu (Eleonora); T. Rafnar (Thorunn); J.P. Rice (John); S.M. Ring (Susan); F. Rivadeneira Ramirez (Fernando); I. Rudan (Igor); C. Sala (Cinzia); V. Salomaa (Veikko); S. Sanna (Serena); D. Schlessinger; N.J. Schork (Nicholas); A. Scuteri (Angelo); A.V. Segrè (Ayellet); A.R. Shuldiner (Alan); N. Soranzo (Nicole); U. Sovio (Ulla); S.R. Srinivasan (Sathanur); D.P. Strachan (David); M.L. Tammesoo; E. Tikkanen (Emmi); D. Toniolo (Daniela); K. Tsui (Kim); L. Tryggvadottir (Laufey); J.P. Tyrer (Jonathan); M. Uda (Manuela); R.M. van Dam (Rob); J.B.J. van Meurs (Joyce); P. Vollenweider (Peter); G. Waeber (Gérard); N.J. Wareham (Nick); D. Waterworth (Dawn); H.E. Wichmann (Heinz Erich); G.A.H.M. Willemsen (Gonneke); J.F. Wilson (James); A.F. Wright (Alan); L. Young (Lauren); G. Zhai (Guangju); W.V. Zhuang; L.J. Bierut (Laura); D.I. Boomsma (Dorret); H.A. Boyd (Heather); L. Crisponi (Laura); E.W. Demerath (Ellen); P. Tikka-Kleemola (Päivi); M.J. Econs (Michael); T.B. Harris (Tamara); D. Hunter (David); R.J.F. Loos (Ruth); A. Metspalu (Andres); G.W. Montgomery (Grant); P.M. Ridker (Paul); T.D. Spector (Tim); E.A. Streeten (Elizabeth); K. Stefansson (Kari); U. Thorsteinsdottir (Unnur); A.G. Uitterlinden (André); E. Widen (Elisabeth); J. Murabito (Joanne); K. Ong (Ken); M.N. Weedon (Michael)

    2010-01-01

    textabstractTo identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30

  6. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    DEFF Research Database (Denmark)

    Elks, Cathy E; Perry, John R B; Sulem, Patrick

    2010-01-01

    To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarc...

  7. Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

    DEFF Research Database (Denmark)

    Mathiassen, Søren; Lauemøller, S L; Ruhwald, Morten

    2001-01-01

    Defined tumor-associated antigens (TAA) are attractive targets for anti-tumor immunotherapy. Here, we describe a novel genome-wide approach to identify multiple TAA from any given tumor. A panel of transplantable thymomas was established from an inbred p53-/- mouse strain. The resulting tumors we...... imprints, which may be used to identify patient-specific arrays of TAA. This may enable a multi-epitope based immunotherapy with improved prospects of clinical tumor rejection....

  8. Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers.

    Science.gov (United States)

    Ash, Samuel Y; Harmouche, Rola; Putman, Rachel K; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Onieva Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

    2017-10-01

    Smoking-related lung injury may manifest on CT scans as both emphysema and interstitial changes. We have developed an automated method to quantify interstitial changes and hypothesized that this measurement would be associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B) polymorphism. Using CT scans from the Genetic Epidemiology of COPD Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated the percentage of the lung occupied by interstitial subtypes. A total of 8,345 participants had clinical and CT scanning data available. A 5% absolute increase in interstitial changes was associated with an absolute decrease in FVC % predicted of 2.47% (P percentage of lung with interstitial changes. Objective interstitial changes on CT scans were associated with impaired lung function, worse quality of life, increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting that these changes may be a marker of susceptibility to smoking-related lung injury, detectable even in those who are healthy by other measures. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  9. To Be or Not to Be Associated: Power study of four statistical modeling approaches to identify parasite associations in cross-sectional studies

    Directory of Open Access Journals (Sweden)

    Elise eVaumourin

    2014-05-01

    Full Text Available A growing number of studies are reporting simultaneous infections by parasites in many different hosts. The detection of whether these parasites are significantly associated is important in medicine and epidemiology. Numerous approaches to detect associations are available, but only a few provide statistical tests. Furthermore, they generally test for an overall detection of association and do not identify which parasite is associated with which other one. Here, we developed a new approach, the association screening approach, to detect the overall and the detail of multi-parasite associations. We studied the power of this new approach and of three other known ones (i.e. the generalized chi-square, the network and the multinomial GLM approaches to identify parasite associations either due to parasite interactions or to confounding factors. We applied these four approaches to detect associations within two populations of multi-infected hosts: 1 rodents infected with Bartonella sp., Babesia microti and Anaplasma phagocytophilum and 2 bovine population infected with Theileria sp. and Babesia sp.. We found that the best power is obtained with the screening model and the generalized chi-square test. The differentiation between associations, which are due to confounding factors and parasite interactions was not possible. The screening approach significantly identified associations between Bartonella doshiae and B. microti, and between T. parva, T. mutans and T. velifera. Thus, the screening approach was relevant to test the overall presence of parasite associations and identify the parasite combinations that are significantly over- or under-represented. Unravelling whether the associations are due to real biological interactions or confounding factors should be further investigated. Nevertheless, in the age of genomics and the advent of new technologies, it is a considerable asset to speed up researches focusing on the mechanisms driving interactions

  10. A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.

    Science.gov (United States)

    Wang, Ke-Sheng; Liu, Xue-Feng; Aragam, Nagesh

    2010-12-01

    Schizophrenia and bipolar disorder both have strong inherited components. Recent studies have indicated that schizophrenia and bipolar disorder may share more than half of their genetic determinants. In this study, we performed a meta-analysis (combined analysis) for genome-wide association data of the Affymetrix Genome-Wide Human SNP array 6.0 to detect genetic variants influencing both schizophrenia and bipolar disorder using European-American samples (653 bipolar cases and 1034 controls, 1172 schizophrenia cases and 1379 controls). The best associated SNP rs11789399 was located at 9q33.1 (p=2.38 × 10(-6), 5.74 × 10(-4), and 5.56 × 10(-9), for schizophrenia, bipolar disorder and meta-analysis of schizophrenia and bipolar disorder, respectively), where one flanking gene, ASTN2 (220kb away) has been associated with attention deficit/hyperactivity disorder and schizophrenia. The next best SNP was rs12201676 located at 6q15 (p=2.67 × 10(-4), 2.12 × 10(-5), 3.88 × 10(-8) for schizophrenia, bipolar disorder and meta-analysis, respectively), near two flanking genes, GABRR1 and GABRR2 (15 and 17kb away, respectively). The third interesting SNP rs802568 was at 7q35 within CNTNAP2 (p=8.92 × 10(-4), 1.38 × 10(-5), and 1.62 × 10(-7) for schizophrenia, bipolar disorder and meta-analysis, respectively). Through meta-analysis, we found two additional associated genes NALCN (the top SNP is rs2044117, p=4.57 × 10(-7)) and NAP5 (the top SNP is rs10496702, p=7.15 × 10(-7)). Haplotype analyses of above five loci further supported the associations with schizophrenia and bipolar disorder. These results provide evidence of common genetic variants influencing schizophrenia and bipolar disorder. These findings will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in schizophrenia and bipolar disorder. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans.

    Science.gov (United States)

    Carty, Cara L; Keene, Keith L; Cheng, Yu-Ching; Meschia, James F; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C; Kittner, Steven J; Rich, Stephen S; Tajuddin, Salman; Zonderman, Alan B; Evans, Michele K; Langefeld, Carl D; Gottesman, Rebecca; Mosley, Thomas H; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, Yongmei; Sale, Michèle M; Dichgans, Martin; Malik, Rainer; Longstreth, W T; Mitchell, Braxton D; Psaty, Bruce M; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B; Fornage, Myriam

    2015-08-01

    The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with Pstroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P=3.9×10(-8)) in African Americans. Nominal associations (Pstroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, and IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B, and ZFHX3) were nominally associated (Pstroke in COMPASS. We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. © 2015 American Heart Association, Inc.

  12. Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles.

    Science.gov (United States)

    Marincevic-Zuniga, Yanara; Dahlberg, Johan; Nilsson, Sara; Raine, Amanda; Nystedt, Sara; Lindqvist, Carl Mårten; Berglund, Eva C; Abrahamsson, Jonas; Cavelier, Lucia; Forestier, Erik; Heyman, Mats; Lönnerholm, Gudmar; Nordlund, Jessica; Syvänen, Ann-Christine

    2017-08-14

    Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

  13. Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles

    Directory of Open Access Journals (Sweden)

    Yanara Marincevic-Zuniga

    2017-08-01

    Full Text Available Abstract Background Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL. In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. Methods We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes. Results We identified 64 unique fusion events distributed among 80 individual patients, of which over 50% have not previously been reported in ALL. Although the majority of the fusion genes were found only in a single patient, we identified several recurrent fusion gene families defined by promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5, and ZNF384, or recurrent fusion genes, such as DUX4-IGH. Our data show that patients harboring these fusion genes displayed characteristic genome-wide DNA methylation and gene expression signatures in addition to distinct patterns in single nucleotide variants and recurrent copy number alterations. Conclusion Our study delineates the fusion gene landscape in pediatric ALL, including both known and novel fusion genes, and highlights fusion gene families with shared molecular etiologies, which may provide additional information for prognosis and therapeutic options in the future.

  14. Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

    Science.gov (United States)

    Aung, Tin; Ozaki, Mineo; Lee, Mei Chin; Schlötzer-Schrehardt, Ursula; Thorleifsson, Gudmar; Mizoguchi, Takanori; Igo, Robert P; Haripriya, Aravind; Williams, Susan E; Astakhov, Yury S; Orr, Andrew C; Burdon, Kathryn P; Nakano, Satoko; Mori, Kazuhiko; Abu-Amero, Khaled; Hauser, Michael; Li, Zheng; Prakadeeswari, Gopalakrishnan; Bailey, Jessica N Cooke; Cherecheanu, Alina Popa; Kang, Jae H; Nelson, Sarah; Hayashi, Ken; Manabe, Shin-Ichi; Kazama, Shigeyasu; Zarnowski, Tomasz; Inoue, Kenji; Irkec, Murat; Coca-Prados, Miguel; Sugiyama, Kazuhisa; Järvelä, Irma; Schlottmann, Patricio; Lerner, S Fabian; Lamari, Hasnaa; Nilgün, Yildirim; Bikbov, Mukharram; Park, Ki Ho; Cha, Soon Cheol; Yamashiro, Kenji; Zenteno, Juan C; Jonas, Jost B; Kumar, Rajesh S; Perera, Shamira A; Chan, Anita S Y; Kobakhidze, Nino; George, Ronnie; Vijaya, Lingam; Do, Tan; Edward, Deepak P; de Juan Marcos, Lourdes; Pakravan, Mohammad; Moghimi, Sasan; Ideta, Ryuichi; Bach-Holm, Daniella; Kappelgaard, Per; Wirostko, Barbara; Thomas, Samuel; Gaston, Daniel; Bedard, Karen; Greer, Wenda L; Yang, Zhenglin; Chen, Xueyi; Huang, Lulin; Sang, Jinghong; Jia, Hongyan; Jia, Liyun; Qiao, Chunyan; Zhang, Hui; Liu, Xuyang; Zhao, Bowen; Wang, Ya-Xing; Xu, Liang; Leruez, Stéphanie; Reynier, Pascal; Chichua, George; Tabagari, Sergo; Uebe, Steffen; Zenkel, Matthias; Berner, Daniel; Mossböck, Georg; Weisschuh, Nicole; Hoja, Ursula; Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Founti, Panayiota; Chatzikyriakidou, Anthi; Pappas, Theofanis; Anastasopoulos, Eleftherios; Lambropoulos, Alexandros; Ghosh, Arkasubhra; Shetty, Rohit; Porporato, Natalia; Saravanan, Vijayan; Venkatesh, Rengaraj; Shivkumar, Chandrashekaran; Kalpana, Narendran; Sarangapani, Sripriya; Kanavi, Mozhgan R; Beni, Afsaneh Naderi; Yazdani, Shahin; Lashay, Alireza; Naderifar, Homa; Khatibi, Nassim; Fea, Antonio; Lavia, Carlo; Dallorto, Laura; Rolle, Teresa; Frezzotti, Paolo; Paoli, Daniela; Salvi, Erika; Manunta, Paolo; Mori, Yosai; Miyata, Kazunori; Higashide, Tomomi; Chihara, Etsuo; Ishiko, Satoshi; Yoshida, Akitoshi; Yanagi, Masahide; Kiuchi, Yoshiaki; Ohashi, Tsutomu; Sakurai, Toshiya; Sugimoto, Takako; Chuman, Hideki; Aihara, Makoto; Inatani, Masaru; Miyake, Masahiro; Gotoh, Norimoto; Matsuda, Fumihiko; Yoshimura, Nagahisa; Ikeda, Yoko; Ueno, Morio; Sotozono, Chie; Jeoung, Jin Wook; Sagong, Min; Park, Kyu Hyung; Ahn, Jeeyun; Cruz-Aguilar, Marisa; Ezzouhairi, Sidi M; Rafei, Abderrahman; Chong, Yaan Fun; Ng, Xiao Yu; Goh, Shuang Ru; Chen, Yueming; Yong, Victor H K; Khan, Muhammad Imran; Olawoye, Olusola O; Ashaye, Adeyinka O; Ugbede, Idakwo; Onakoya, Adeola; Kizor-Akaraiwe, Nkiru; Teekhasaenee, Chaiwat; Suwan, Yanin; Supakontanasan, Wasu; Okeke, Suhanya; Uche, Nkechi J; Asimadu, Ifeoma; Ayub, Humaira; Akhtar, Farah; Kosior-Jarecka, Ewa; Lukasik, Urszula; Lischinsky, Ignacio; Castro, Vania; Grossmann, Rodolfo Perez; Megevand, Gordana Sunaric; Roy, Sylvain; Dervan, Edward; Silke, Eoin; Rao, Aparna; Sahay, Priti; Fornero, Pablo; Cuello, Osvaldo; Sivori, Delia; Zompa, Tamara; Mills, Richard A; Souzeau, Emmanuelle; Mitchell, Paul; Wang, Jie Jin; Hewitt, Alex W; Coote, Michael; Crowston, Jonathan G; Astakhov, Sergei Y; Akopov, Eugeny L; Emelyanov, Anton; Vysochinskaya, Vera; Kazakbaeva, Gyulli; Fayzrakhmanov, Rinat; Al-Obeidan, Saleh A; Owaidhah, Ohoud; Aljasim, Leyla Ali; Chowbay, Balram; Foo, Jia Nee; Soh, Raphael Q; Sim, Kar Seng; Xie, Zhicheng; Cheong, Augustine W O; Mok, Shi Qi; Soo, Hui Meng; Chen, Xiao Yin; Peh, Su Qin; Heng, Khai Koon; Husain, Rahat; Ho, Su-Ling; Hillmer, Axel M; Cheng, Ching-Yu; Escudero-Domínguez, Francisco A; González-Sarmiento, Rogelio; Martinon-Torres, Frederico; Salas, Antonio; Pathanapitoon, Kessara; Hansapinyo, Linda; Wanichwecharugruang, Boonsong; Kitnarong, Naris; Sakuntabhai, Anavaj; Nguyn, Hip X; Nguyn, Giang T T; Nguyn, Trình V; Zenz, Werner; Binder, Alexander; Klobassa, Daniela S; Hibberd, Martin L; Davila, Sonia; Herms, Stefan; Nöthen, Markus M; Moebus, Susanne; Rautenbach, Robyn M; Ziskind, Ari; Carmichael, Trevor R; Ramsay, Michele; Álvarez, Lydia; García, Montserrat; González-Iglesias, Héctor; Rodríguez-Calvo, Pedro P; Fernández-Vega Cueto, Luis; Oguz, Çilingir; Tamcelik, Nevbahar; Atalay, Eray; Batu, Bilge; Aktas, Dilek; Kasım, Burcu; Wilson, M Roy; Coleman, Anne L; Liu, Yutao; Challa, Pratap; Herndon, Leon; Kuchtey, Rachel W; Kuchtey, John; Curtin, Karen; Chaya, Craig J; Crandall, Alan; Zangwill, Linda M; Wong, Tien Yin; Nakano, Masakazu; Kinoshita, Shigeru; den Hollander, Anneke I; Vesti, Eija; Fingert, John H; Lee, Richard K; Sit, Arthur J

    2017-07-01

    Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10 -14 ) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10 -8 ). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

  15. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

    Science.gov (United States)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael J; Maranian, Mel J; Bolla, Manjeet K; Wang, Qin; Shah, Mitul; Perkins, Barbara J; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Nielsen, Sune F; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G; Whittemore, Alice S; John, Esther M; Malone, Kathleen E; Gammon, Marilie D; Santella, Regina M; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F; Casey, Graham; Hunter, David J; Gapstur, Susan M; Gaudet, Mia M; Diver, W Ryan; Haiman, Christopher A; Schumacher, Fredrick; Henderson, Brian E; Le Marchand, Loic; Berg, Christine D; Chanock, Stephen J; Figueroa, Jonine; Hoover, Robert N; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guénel, Pascal; Truong, Thérèse; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; Tan, Gie-Hooi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John W M; Collée, J Margriet; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N; Nord, Silje; Alnaes, Grethe I Grenaker; Giles, Graham G; Milne, Roger L; McLean, Catriona; Canzian, Federico; Trichopoulos, Dimitrios; Peeters, Petra; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Swerdlow, Anthony J; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V; Dörk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul P D P; Kraft, Peter; Dunning, Alison M; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F

    2015-04-01

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

  16. Brain structure-function associations identified in large-scale neuroimaging data.

    Science.gov (United States)

    Yang, Zhi; Qiu, Jiang; Wang, Peipei; Liu, Rui; Zuo, Xi-Nian

    2016-12-01

    The relationships between structural and functional measures of the human brain remain largely unknown. A majority of our limited knowledge regarding structure-function associations has been obtained through comparisons between specific groups of patients and healthy controls. Unfortunately, a direct and complete view of the associations across multiple structural and functional metrics in normal population is missing. We filled this gap by learning cross-individual co-variance among structural and functional measures using large-scale neuroimaging datasets. A discover-confirm scheme was applied to two independent samples (N = 184 and N = 340) of multi-modal neuroimaging datasets. A data mining tool, gRAICAR, was employed in the discover stage to generate quantitative and unbiased hypotheses of the co-variance among six functional and six structural imaging metrics. These hypotheses were validated using an independent dataset in the confirm stage. Fifteen multi-metric co-variance units, representing different co-variance relationships among the 12 metrics, were reliable across the two sets of neuroimaging datasets. The reliable co-variance units were summarized into a database, where users can select any location on the cortical map of any metric to examine the co-varying maps with the other 11 metrics. This database characterized the six functional metrics based on their co-variance with structural metrics, and provided a detailed reference to connect previous findings using different metrics and to predict maps of unexamined metrics. Gender, age, and handedness were associated to the co-variance units, and a sub-study of schizophrenia demonstrated the usefulness of the co-variance database.

  17. Genome-wide association study identifies vitamin B5 biosynthesis as a host specificity factor in Campylobacter

    OpenAIRE

    Sheppard, Samuel K.; Didelot, Xavier; Meric, Guillaume; Torralbo, Alicia; Jolley, Keith A.; Kelly, David J.; Bentley, Stephen D.; Maiden, Martin C. J.; Parkhill, Julian; Falush, Daniel

    2013-01-01

    Genome-wide association studies have the potential to identify causal genetic factors underlying important phenotypes but have rarely been performed in bacteria. We present an association mapping method that takes into account the clonal population structure of bacteria and is applicable to both core and accessory genome variation. Campylobacter is a common cause of human gastroenteritis as a consequence of its proliferation in multiple farm animal species and its transmission via contaminate...

  18. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  19. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    DEFF Research Database (Denmark)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara

    2013-01-01

    ), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER...

  20. Thyroid disease awareness is associated with high rates of identifying subjects with previously undiagnosed thyroid dysfunction.

    Science.gov (United States)

    Canaris, Gay J; Tape, Thomas G; Wigton, Robert S

    2013-04-16

    Conventional screening for hypothyroidism is controversial. Although hypothyroidism is underdiagnosed, many organizations do not recommend screening, citing low disease prevalence in unselected populations. We studied attendees at a thyroid health fair, hypothesizing that certain patient characteristics would enhance the yield of testing. We carried out an observational study of participants at a Michigan health fair that focused on thyroid disease. We collected patient-reported symptoms and demographics by questionnaire, and correlated these with the TSH values obtained through the health fair. 794 of 858 health fair attendees participated. Most were women, and over 40% reported a family history of thyroid disease. We identified 97 (12.2%) participants with previously unknown thyroid dysfunction. No symptom or combination of symptoms discriminated between hypothyroid and euthyroid individuals. Hypothyroid and euthyroid participants in the health fair reported each symptom with a similar prevalence (p > 0.01), a prevalence which was very high. In fact, when compared with a previously published case-control study that reported symptoms, the euthyroid health fair participants reported a higher symptom prevalence (range 3.9% to 66.3%, mean 31.5%), than the euthyroid individuals from the case-control study (range 2% to 54%, mean 17.4%). A high proportion of previously undiagnosed thyroid disease was identified at this health fair. We initially hypothesized symptoms would distinguish between thyroid function states. However, this was not the case in this health fair screening population. The prevalence of reported symptoms was similar and high in both euthyroid and hypothyroid participants. Because attendees were self-selected, it is possible that this health fair that focused on thyroid disease attracted participants specifically concerned about thyroid health. Despite the lack of symptom discrimination, the much higher prevalence of hypothyroidism in this study

  1. Comparative genomics of pathogenic lineages of Vibrio nigripulchritudo identifies virulence-associated traits

    Science.gov (United States)

    Goudenège, David; Labreuche, Yannick; Krin, Evelyne; Ansquer, Dominique; Mangenot, Sophie; Calteau, Alexandra; Médigue, Claudine; Mazel, Didier; Polz, Martin F; Le Roux, Frédérique

    2013-01-01

    Vibrio nigripulchritudo is an emerging pathogen of farmed shrimp in New Caledonia and other regions in the Indo-Pacific. The molecular determinants of V. nigripulchritudo pathogenicity are unknown; however, molecular epidemiological studies have suggested that pathogenicity is linked to particular lineages. Here, we performed high-throughput sequencing-based comparative genome analysis of 16 V. nigripulchritudo strains to explore the genomic diversity and evolutionary history of pathogen-containing lineages and to identify pathogen-specific genetic elements. Our phylogenetic analysis revealed three pathogen-containing V. nigripulchritudo clades, including two clades previously identified from New Caledonia and one novel clade comprising putatively pathogenic isolates from septicemic shrimp in Madagascar. The similar genetic distance between the three clades indicates that they have diverged from an ancestral population roughly at the same time and recombination analysis indicates that these genomes have, in the past, shared a common gene pool and exchanged genes. As each contemporary lineage is comprised of nearly identical strains, comparative genomics allowed differentiation of genetic elements specific to shrimp pathogenesis of varying severity. Notably, only a large plasmid present in all highly pathogenic (HP) strains encodes a toxin. Although less/non-pathogenic strains contain related plasmids, these are differentiated by a putative toxin locus. Expression of this gene by a non-pathogenic V. nigripulchritudo strain resulted in production of toxic culture supernatant, normally an exclusive feature of HP strains. Thus, this protein, here termed ‘nigritoxin', is implicated to an extent that remains to be precisely determined in the toxicity of V. nigripulchritudo. PMID:23739050

  2. CMDR based differential evolution identifies the epistatic interaction in genome-wide association studies.

    Science.gov (United States)

    Yang, Cheng-Hong; Chuang, Li-Yeh; Lin, Yu-Da

    2017-08-01

    Detecting epistatic interactions in genome-wide association studies (GWAS) is a computational challenge. Such huge numbers of single-nucleotide polymorphism (SNP) combinations limit the some of the powerful algorithms to be applied to detect the potential epistasis in large-scale SNP datasets. We propose a new algorithm which combines the differential evolution (DE) algorithm with a classification based multifactor-dimensionality reduction (CMDR), termed DECMDR. DECMDR uses the CMDR as a fitness measure to evaluate values of solutions in DE process for scanning the potential statistical epistasis in GWAS. The results indicated that DECMDR outperforms the existing algorithms in terms of detection success rate by the large simulation and real data obtained from the Wellcome Trust Case Control Consortium. For running time comparison, DECMDR can efficient to apply the CMDR to detect the significant association between cases and controls amongst all possible SNP combinations in GWAS. DECMDR is freely available at https://goo.gl/p9sLuJ . chuang@isu.edu.tw or e0955767257@yahoo.com.tw. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Association analysis identifies Melampsora ×columbiana poplar leaf rust resistance SNPs.

    Directory of Open Access Journals (Sweden)

    Jonathan La Mantia

    Full Text Available Populus species are currently being domesticated through intensive time- and resource-dependent programs for utilization in phytoremediation, wood and paper products, and conversion to biofuels. Poplar leaf rust disease can greatly reduce wood volume. Genetic resistance is effective in reducing economic losses but major resistance loci have been race-specific and can be readily defeated by the pathogen. Developing durable disease resistance requires the identification of non-race-specific loci. In the presented study, area under the disease progress curve was calculated from natural infection of Melampsora ×columbiana in three consecutive years. Association analysis was performed using 412 P. trichocarpa clones genotyped with 29,355 SNPs covering 3,543 genes. We found 40 SNPs within 26 unique genes significantly associated (permutated P<0.05 with poplar rust severity. Moreover, two SNPs were repeated in all three years suggesting non-race-specificity and three additional SNPs were differentially expressed in other poplar rust interactions. These five SNPs were found in genes that have orthologs in Arabidopsis with functionality in pathogen induced transcriptome reprogramming, Ca²⁺/calmodulin and salicylic acid signaling, and tolerance to reactive oxygen species. The additive effect of non-R gene functional variants may constitute high levels of durable poplar leaf rust resistance. Therefore, these findings are of significance for speeding the genetic improvement of this long-lived, economically important organism.

  4. Identifying factors associated with hospital readmissions among stroke patients in Taipei.

    Science.gov (United States)

    Chuang, Kun-Yang; Wu, Shwu-Chong; Ma, Ai-Hsuan Sandra; Chen, Yu-Hui; Wu, Chen-Long

    2005-06-01

    Hospital readmissions contribute significantly to the cost of medical care, and may reflect unresolved problems at discharge or a lack of resources in post-hospital care. The purpose of this paper is to assess the effects of patient characteristics at discharge, the need for nursing care, discharge planning program, post-hospital care arrangements, and caregiver characteristics on readmissions of stroke patients. Patients discharged from neurological wards in seven hospitals in the Taipei area were recruited into the study. Surveys were conducted before their discharge, and at one month after discharge. Of the 489 patients included in the study, 24.3% were readmitted. After controlling for other variables, factors associated with readmissions were number of limitations in activities of daily living (ADL), first incidence of stroke, the need for wound nursing care, the adoption of a care plan, and the discharge locations. Contrary to expectation, age, length of stay, counseling before discharge, and caregiver burden were not associated with readmissions. The findings of this study indicate that ADL limitation is an effective predictor of readmissions. Increasing home nursing resources to meet the demand for wound nursing care may also be effective in reducing readmissions. Discharging patients into institutions for a short period of time may also prove to be more economically viable due to the reduction in readmissions.

  5. An Immunochip-based interrogation of scleroderma susceptibility variants identifies a novel association at DNASE1L3.

    Science.gov (United States)

    Zochling, Jane; Newell, Felicity; Charlesworth, Jac C; Leo, Paul; Stankovich, Jim; Cortes, Adrian; Zhou, Yuan; Stevens, Wendy; Sahhar, Joanne; Roddy, Janet; Nash, Peter; Tymms, Kathleen; Rischmueller, Maureen; Lester, Sue; Proudman, Susanna; Brown, Matthew A

    2014-10-21

    The aim of the study was to interrogate the genetic architecture and autoimmune pleiotropy of scleroderma susceptibility in the Australian population. We genotyped individuals from a well-characterized cohort of Australian scleroderma patients with the Immunochip, a custom array enriched for single nucleotide polymorphisms (SNPs) at immune loci. Controls were taken from the 1958 British Birth Cohort. After data cleaning and adjusting for population stratification the final dataset consisted of 486 cases, 4,458 controls and 146,525 SNPs. Association analyses were conducted using logistic regression in PLINK. A replication study was performed using 833 cases and 1,938 controls. A total of eight loci with suggestive association (P <10-4.5) were identified, of which five showed significant association in the replication cohort (HLA-DRB1, DNASE1L3, STAT4, TNP03-IRF5 and VCAM1). The most notable findings were at the DNASE1L3 locus, previously associated with systemic lupus erythematosus, and VCAM1, a locus not previously associated with human disease. This study identified a likely functional variant influencing scleroderma susceptibility at the DNASE1L3 locus; a missense polymorphism rs35677470 in DNASE1L3, with an odds ratio of 2.35 (P = 2.3 × 10(-10)) in anti-centromere antibody (ACA) positive cases. This pilot study has confirmed previously reported scleroderma associations, revealed further genetic overlap between scleroderma and systemic lupus erythematosus, and identified a putative novel scleroderma susceptibility locus.

  6. Meta-analysis of genome-wide association studies identifies genetic risk factors for stroke in African-Americans

    Science.gov (United States)

    Carty, Cara L.; Keene, Keith L.; Cheng, Yu-Ching; Meschia, James F.; Chen, Wei-Min; Nalls, Mike; Bis, Joshua C.; Kittner, Steven J.; Rich, Stephen S.; Tajuddin, Salman; Zonderman, Alan B.; Evans, Michele K.; Langefeld, Carl D.; Gottesman, Rebecca; Mosley, Thomas H.; Shahar, Eyal; Woo, Daniel; Yaffe, Kristine; Liu, YongMei; Sale, Michèle M.; Dichgans, Martin; Malik, Rainer; Longstreth, WT; Mitchell, Braxton D.; Psaty, Bruce M.; Kooperberg, Charles; Reiner, Alexander; Worrall, Bradford B.; Fornage, Myriam

    2015-01-01

    Background and Purpose The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African-Americans despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population genome-wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods Using METAL, we conducted meta-analyses of GWAS in 14,746 African-Americans (1,365 ischemic and 1,592 total stroke cases) from COMPASS, and tested SNPs with Pstroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613, P=3.9×10−8) in African-Americans. Nominal associations (Pstroke were observed for 18 variants in or near genes implicated in cell cycle/ mRNA pre-splicing (PTPRG, CDC5L), platelet function (HPS4), blood-brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B and ZFHX3) were nominally associated (Pstroke in COMPASS. Conclusions We identified a novel SNP associated with total stroke in African-Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African-Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations. PMID:26089329

  7. Oil palm (Elaeis guineensis Jacq.) tissue culture ESTs: identifying genes associated with callogenesis and embryogenesis.

    Science.gov (United States)

    Low, Eng-Ti L; Alias, Halimah; Boon, Soo-Heong; Shariff, Elyana M; Tan, Chi-Yee A; Ooi, Leslie Cl; Cheah, Suan-Choo; Raha, Abdul-Rahim; Wan, Kiew-Lian; Singh, Rajinder

    2008-05-29

    Oil palm (Elaeis guineensis Jacq.) is one of the most important oil bearing crops in the world. However, genetic improvement of oil palm through conventional breeding is extremely slow and costly, as the breeding cycle can take up to 10 years. This has brought about interest in vegetative propagation of oil palm. Since the introduction of oil palm tissue culture in the 1970s, clonal propagation has proven to be useful, not only in producing uniform planting materials, but also in the development of the genetic engineering programme. Despite considerable progress in improving the tissue culture techniques, the callusing and embryogenesis rates from proliferating callus cultures remain very low. Thus, understanding the gene diversity and expression profiles in oil palm tissue culture is critical in increasing the efficiency of these processes. A total of 12 standard cDNA libraries, representing three main developmental stages in oil palm tissue culture, were generated in this study. Random sequencing of clones from these cDNA libraries generated 17,599 expressed sequence tags (ESTs). The ESTs were analysed, annotated and assembled to generate 9,584 putative unigenes distributed in 3,268 consensi and 6,316 singletons. These unigenes were assigned putative functions based on similarity and gene ontology annotations. Cluster analysis, which surveyed the relatedness of each library based on the abundance of ESTs in each consensus, revealed that lipid transfer proteins were highly expressed in embryogenic tissues. A glutathione S-transferase was found to be highly expressed in non-embryogenic callus. Further analysis of the unigenes identified 648 non-redundant simple sequence repeats and 211 putative full-length open reading frames. This study has provided an overview of genes expressed during oil palm tissue culture. Candidate genes with expression that are modulated during tissue culture were identified. However, in order to confirm whether these genes are suitable as

  8. Oil palm (Elaeis guineensis Jacq. tissue culture ESTs: Identifying genes associated with callogenesis and embryogenesis

    Directory of Open Access Journals (Sweden)

    Ooi Leslie CL

    2008-05-01

    Full Text Available Abstract Background Oil palm (Elaeis guineensis Jacq. is one of the most important oil bearing crops in the world. However, genetic improvement of oil palm through conventional breeding is extremely slow and costly, as the breeding cycle can take up to 10 years. This has brought about interest in vegetative propagation of oil palm. Since the introduction of oil palm tissue culture in the 1970s, clonal propagation has proven to be useful, not only in producing uniform planting materials, but also in the development of the genetic engineering programme. Despite considerable progress in improving the tissue culture techniques, the callusing and embryogenesis rates from proliferating callus cultures remain very low. Thus, understanding the gene diversity and expression profiles in oil palm tissue culture is critical in increasing the efficiency of these processes. Results A total of 12 standard cDNA libraries, representing three main developmental stages in oil palm tissue culture, were generated in this study. Random sequencing of clones from these cDNA libraries generated 17,599 expressed sequence tags (ESTs. The ESTs were analysed, annotated and assembled to generate 9,584 putative unigenes distributed in 3,268 consensi and 6,316 singletons. These unigenes were assigned putative functions based on similarity and gene ontology annotations. Cluster analysis, which surveyed the relatedness of each library based on the abundance of ESTs in each consensus, revealed that lipid transfer proteins were highly expressed in embryogenic tissues. A glutathione S-transferase was found to be highly expressed in non-embryogenic callus. Further analysis of the unigenes identified 648 non-redundant simple sequence repeats and 211 putative full-length open reading frames. Conclusion This study has provided an overview of genes expressed during oil palm tissue culture. Candidate genes with expression that are modulated during tissue culture were identified. However

  9. Comparative Genomics Identifies Epidermal Proteins Associated with the Evolution of the Turtle Shell.

    Science.gov (United States)

    Holthaus, Karin Brigit; Strasser, Bettina; Sipos, Wolfgang; Schmidt, Heiko A; Mlitz, Veronika; Sukseree, Supawadee; Weissenbacher, Anton; Tschachler, Erwin; Alibardi, Lorenzo; Eckhart, Leopold

    2016-03-01

    The evolution of reptiles, birds, and mammals was associated with the origin of unique integumentary structures. Studies on lizards, chicken, and humans have suggested that the evolution of major structural proteins of the outermost, cornified layers of the epidermis was driven by the diversification of a gene cluster called Epidermal Differentiation Complex (EDC). Turtles have evolved unique defense mechanisms that depend on mechanically resilient modifications of the epidermis. To investigate whether the evolution of the integument in these reptiles was associated with specific adaptations of the sequences and expression patterns of EDC-related genes, we utilized newly available genome sequences to determine the epidermal differentiation gene complement of turtles. The EDC of the western painted turtle (Chrysemys picta bellii) comprises more than 100 genes, including at least 48 genes that encode proteins referred to as beta-keratins or corneous beta-proteins. Several EDC proteins have evolved cysteine/proline contents beyond 50% of total amino acid residues. Comparative genomics suggests that distinct subfamilies of EDC genes have been expanded and partly translocated to loci outside of the EDC in turtles. Gene expression analysis in the European pond turtle (Emys orbicularis) showed that EDC genes are differentially expressed in the skin of the various body sites and that a subset of beta-keratin genes within the EDC as well as those located outside of the EDC are expressed predominantly in the shell. Our findings give strong support to the hypothesis that the evolutionary innovation of the turtle shell involved specific molecular adaptations of epidermal differentiation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants.

    Science.gov (United States)

    Allum, Fiona; Shao, Xiaojian; Guénard, Frédéric; Simon, Marie-Michelle; Busche, Stephan; Caron, Maxime; Lambourne, John; Lessard, Julie; Tandre, Karolina; Hedman, Åsa K; Kwan, Tony; Ge, Bing; Rönnblom, Lars; McCarthy, Mark I; Deloukas, Panos; Richmond, Todd; Burgess, Daniel; Spector, Timothy D; Tchernof, André; Marceau, Simon; Lathrop, Mark; Vohl, Marie-Claude; Pastinen, Tomi; Grundberg, Elin

    2015-05-29

    Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.

  11. Genome-wide Association Study Identifies African-Specific Susceptibility Loci in African Americans with Inflammatory Bowel Disease

    Science.gov (United States)

    Brant, Steven R.; Okou, David T.; Simpson, Claire L.; Cutler, David J.; Haritunians, Talin; Bradfield, Jonathan P.; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W.; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J.; Klapproth, Jan-Micheal A.; Quiros, Antonio J.; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S.; Baldassano, Robert N.; Dudley-Brown, Sharon; Cross, Raymond K.; Dassopoulos, Themistocles; Denson, Lee A.; Dhere, Tanvi A.; Dryden, Gerald W.; Hanson, John S.; Hou, Jason K.; Hussain, Sunny Z.; Hyams, Jeffrey S.; Isaacs, Kim L.; Kader, Howard; Kappelman, Michael D.; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S.; Kuemmerle, John F.; Kwon, John H.; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E.; Newberry, Rodney D.; Osuntokun, Bankole O.; Patel, Ashish S.; Saeed, Shehzad A.; Targan, Stephan R.; Valentine, John F.; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Hakonarson, Hakon; Zwick, Michael E.; McGovern, Dermot P.B.; Kugathasan, Subra

    2016-01-01

    Background & Aims The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. Methods We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified [IBD-U]) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P<5.0×10−8 in meta-analysis with a nominal evidence (P<.05) in each scan were considered to have genome-wide significance. Results We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance associations for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P<1.6×10−6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B, PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. Conclusions We performed a genome-wide association study of African Americans with IBD and identified loci associated with CD and UC in only this population; we also replicated loci identified in European populations. The detection of variants associated with IBD risk in only

  12. Identifying gene-gene interactions that are highly associated with Body Mass Index using Quantitative Multifactor Dimensionality Reduction (QMDR)

    NARCIS (Netherlands)

    De, Rishika; Verma, Shefali S; Drenos, Fotios; Holzinger, Emily R; Holmes, Michael V; Hall, Molly A; Crosslin, David R; Carrell, David S; Hakonarson, Hakon; Jarvik, Gail; Larson, Eric; Pacheco, Jennifer A; Rasmussen-Torvik, Laura J; Moore, Carrie B; Asselbergs, Folkert W; Moore, Jason H; Ritchie, Marylyn D; Keating, Brendan J; Gilbert-Diamond, Diane

    2015-01-01

    BACKGROUND: Despite heritability estimates of 40-70 % for obesity, less than 2 % of its variation is explained by Body Mass Index (BMI) associated loci that have been identified so far. Epistasis, or gene-gene interactions are a plausible source to explain portions of the missing heritability of

  13. A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis

    NARCIS (Netherlands)

    Schaefer, A.S.; Richter, G.M.; Nothnagel, M.; Manke, T.; Dommisch, H.; Jacobs, G.; Arlt, A.; Rosenstiel, P.; Noack, B.; Groessner-Schreiber, B.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2010-01-01

    Periodontitis is a widespread, complex inflammatory disease of the mouth, which results in a loss of gingival tissue and alveolar bone, with aggressive periodontitis (AgP) as its most severe form. To identify genetic risk factors for periodontitis, we conducted a genome-wide association study in

  14. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

    DEFF Research Database (Denmark)

    McKay, James D.; Hung, Rayjean J.; Han, Younghun

    2017-01-01

    Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association ...

  15. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.

    NARCIS (Netherlands)

    Lan, Q.; Hsiung, C.A.; Matsuo, K.; Hong, Y.C.; Seow, A.; Wang, Z.; Hosgood, H.D.; Chen, K.; Wang, J.C.; Chatterjee, N.; Hu, W.; Wong, M.P.; Zheng, W.; Caporaso, N.; Park, J.Y.; Chen, C.J.; Kim, Y.H.; Kim, Y.T.; Landi, M.T.; Shen, H.; Lawrence, C.; Burdett, L.; Yeager, M.; Yuenger, J.; Jacobs, K.B.; Chang, I.S.; Mitsudomi, T.; Kim, H.N.; Chang, G.C.; Bassig, B.A.; Tucker, M.; Wei, F.; Yin, Y.; Wu, C.; An, S.J.; Qian, B.; Lee, V.H.; Lu, D.; Liu, J.; Jeon, H.S.; Hsiao, C.F.; Sung, J.S.; Kim, J.H.; Gao, Y.T.; Tsai, Y.H.; Jung, Y.J.; Guo, H.; Hu, Z.; Hutchinson, A.; Wang, W.C.; Klein, R.; Chung, C.C.; Oh, I.J.; Chen, K.Y.; Berndt, S.I.; He, X.; Wu, W.; Chang, J.; Zhang, X.C.; Huang, M.S.; Zheng, H.; Wang, J.; Zhao, X.|info:eu-repo/dai/nl/413577805; Li, Y.; Choi, J.E.; Su, W.C.; Park, K.H.; Sung, S.W.; Shu, X.O.; Chen, Y.M.; Liu, L.; Kang, C.H.; Hu, L.; Chen, C.H.; Pao, W.; Kim, Y.C.; Yang, T.Y.; Xu, J.; Guan, P.; Tan, W.; Su, J.; Wang, C.L.; Li, H.; Sihoe, A.D.; Zhao, Z.|info:eu-repo/dai/nl/304120995; Chen, Y.; Choi, Y.Y.; Hung, J.Y.; Kim, J.S.; Yoon, H.I.; Cai, Q.; Lin, C.C.; Park, I.K.; Xu, P.; Dong, J.; Kim, C.; He, Q; Perng, R.P.; Kohno, T.; Kweon, S.S.; Chen, C.Y.; Vermeulen, R.|info:eu-repo/dai/nl/216532620; Wu, J.; Lim, W.Y.; Chen, K.C.; Chow, W.H.; Ji, B.T.; Chan, J.K.; Chu, M.; Li, Y.J.; Yokota, J.; Li, J.; Chen, H.; Xiang, Y.B.; Yu, C.J.; Kunitoh, H.; Wu, G.; Jin, L.; Lo, Y.L.; Shiraishi, K.; Chen, Y.H.; Lin, H.C.; Wu, T.; WU, Y.; Yang, P.C.; Zhou, B.; Shin, M.H.; Fraumeni, J.F.; Lin, D.; Chanock, S.J.; Rothman, N.

    2012-01-01

    To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland

  16. Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins.

    Directory of Open Access Journals (Sweden)

    Zhenliang Chen

    Full Text Available Since milk yield is a highly important economic trait in dairy cattle, the genome-wide association study (GWAS is vital to explain the genetic architecture underlying milk yield and to perform marker-assisted selection (MAS. In this study, we adopted a haplotype-based empirical Bayesian GWAS to identify the loci and candidate genes for milk yield. A total of 1 092 Holstein cows were sequenced by using the genotyping by genome reducing and sequencing (GGRS method. After filtering, 164 312 high-confidence SNPs and 13 476 haplotype blocks were identified to use for GWAS. The results indicated that 17 blocks were significantly associated with milk yield. We further identified the nearest gene of each haplotype block and annotated the genes with milk-associated quantitative trait locus (QTL intervals and ingenuity pathway analysis (IPA networks. Our analysis showed that four genes, DLGAP1, AP2B1, ITPR2 and THBS4, have relationships with milk yield, while another three, ARHGEF4, TDRD1 and KIF19, were inferred to have potential relationships. Additionally, a network derived from the IPA containing one inferred (ARHGEF4 and all four confirmed genes likely regulates milk yield. Our findings add to the understanding of identifying the causal genes underlying milk production traits and could guide follow up studies for further confirmation of the associated genes, pathways and biological networks.

  17. Functional SNP associated with birth weight in independent populations identified with a permutation step added to GBLUP-GWAS

    Science.gov (United States)

    This study was conducted as an initial assessment of a newly available genotyping assay containing about 34,000 common SNP included on previous SNP chips, and 199,000 sequence variants predicted to affect gene function. Objectives were to identify functional variants associated with birth weight in...

  18. Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

    DEFF Research Database (Denmark)

    Mathiassen, S; Lauemøller, S L; Ruhwald, M

    2001-01-01

    Defined tumor-associated antigens (TAA) are attractive targets for anti-tumor immunotherapy. Here, we describe a novel genome-wide approach to identify multiple TAA from any given tumor. A panel of transplantable thymomas was established from an inbred p53-/- mouse strain. The resulting tumors were...

  19. Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

    Science.gov (United States)

    Yao, Youyuan; Xu, Miao; Liang, Liming; Zhang, Haojiong; Xu, Ruihua; Feng, Qisheng; Feng, Lin; Luo, Bing; Zeng, Yi-Xin

    2017-10-01

    Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

  20. Identifying genetic marker sets associated with phenotypes via an efficient adaptive score test

    KAUST Repository

    Cai, T.

    2012-06-25

    In recent years, genome-wide association studies (GWAS) and gene-expression profiling have generated a large number of valuable datasets for assessing how genetic variations are related to disease outcomes. With such datasets, it is often of interest to assess the overall effect of a set of genetic markers, assembled based on biological knowledge. Genetic marker-set analyses have been advocated as more reliable and powerful approaches compared with the traditional marginal approaches (Curtis and others, 2005. Pathways to the analysis of microarray data. TRENDS in Biotechnology 23, 429-435; Efroni and others, 2007. Identification of key processes underlying cancer phenotypes using biologic pathway analysis. PLoS One 2, 425). Procedures for testing the overall effect of a marker-set have been actively studied in recent years. For example, score tests derived under an Empirical Bayes (EB) framework (Liu and others, 2007. Semiparametric regression of multidimensional genetic pathway data: least-squares kernel machines and linear mixed models. Biometrics 63, 1079-1088; Liu and others, 2008. Estimation and testing for the effect of a genetic pathway on a disease outcome using logistic kernel machine regression via logistic mixed models. BMC bioinformatics 9, 292-2; Wu and others, 2010. Powerful SNP-set analysis for case-control genome-wide association studies. American Journal of Human Genetics 86, 929) have been proposed as powerful alternatives to the standard Rao score test (Rao, 1948. Large sample tests of statistical hypotheses concerning several parameters with applications to problems of estimation. Mathematical Proceedings of the Cambridge Philosophical Society, 44, 50-57). The advantages of these EB-based tests are most apparent when the markers are correlated, due to the reduction in the degrees of freedom. In this paper, we propose an adaptive score test which up- or down-weights the contributions from each member of the marker-set based on the Z-scores of

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

    Science.gov (United States)

    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; 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; Davies, Gail; 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

    2016-06-01

    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 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 associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms 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 or pancreas tissues are strongly enriched for association.

  2. A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder.

    Science.gov (United States)

    Ma, Emily; Vetter, Joel; Bliss, Laura; Lai, H Henry; Mysorekar, Indira U; Jain, Sanjay

    2016-07-01

    Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis. Copyright © 2016 the American Physiological Society.

  3. Gene expression profiling in whole blood identifies distinct biological pathways associated with obesity

    Directory of Open Access Journals (Sweden)

    Gorman Shelby A

    2010-12-01

    Full Text Available Abstract Background Obesity is reaching epidemic proportions and represents a significant risk factor for cardiovascular disease, diabetes, and cancer. Methods To explore the relationship between increased body mass and gene expression in blood, we conducted whole-genome expression profiling of whole blood from seventeen obese and seventeen well matched lean subjects. Gene expression data was analyzed at the individual gene and pathway level and a preliminary assessment of the predictive value of blood gene expression profiles in obesity was carried out. Results Principal components analysis of whole-blood gene expression data from obese and lean subjects led to efficient separation of the two cohorts. Pathway analysis by gene-set enrichment demonstrated increased transcript levels for genes belonging to the "ribosome", "apoptosis" and "oxidative phosphorylation" pathways in the obese cohort, consistent with an altered metabolic state including increased protein synthesis, enhanced cell death from proinflammatory or lipotoxic stimuli, and increased energy demands. A subset of pathway-specific genes acted as efficient predictors of obese or lean class membership when used in Naive Bayes or logistic regression based classifiers. Conclusion This study provides a comprehensive characterization of the whole blood transcriptome in obesity and demonstrates that the investigation of gene expression profiles from whole blood can inform and illustrate the biological processes related to regulation of body mass. Additionally, the ability of pathway-related gene expression to predict class membership suggests the feasibility of a similar approach for identifying clinically useful blood-based predictors of weight loss success following dietary or surgical interventions.

  4. Transposon mutagenesis identifies novel genes associated with Staphylococcus aureus persister formation

    Directory of Open Access Journals (Sweden)

    Wang ewenjie

    2015-12-01

    Full Text Available Pathogenic bacterial persisters are responsible for the recalcitrance of chronic and persistent infections to antimicrobial therapy. Although the mechanisms of persister formation and survival have been widely studied in Escherichia coli, persistence mechanisms in S. aureus remain largely unknown. Here, we screened a transposon mutant library of a clinical methicillin-resistant Staphylococcus aureus(MRSA)strain, USA500 (ST8, under antibiotic pressure and identified 13 genes whose insertion mutations resulted in a defect in persistence. These candidate genes were further confirmed by evaluating the survival of the mutants upon exposure to levofloxacin and several other stress conditions. We found 13 insertion mutants with significantly lower persister numbers under several stress conditions, including sdhA, sdhB, ureG, mnhG1, fbaA, ctaB, clpX, parE, HOU_0223, HOU_0587, HOU_2091, HOU_2315 and HOU_2346, which mapped into pathways of oxidative phosphorylation, TCA cycle, glycolysis, cell cycle and ABC transporters, suggesting that these genes and pathways may play an important role in persister formation and survival. The newly constructed knockout strains of ureG, sdhA and sdhB and their complemented strains were also tested for defect in persisters following exposure to levofloxacin and several other stress conditions. The results from these experiments were consistent with the screening results, which indicated that deletion of these genes in MRSA USA500 leads to persister defect. These findings provide novel insights into the mechanisms of persister formation and survival in S. aureus and offer new targets for the development of persister-directed antibiotics for the improved treatment of chronic and persistent infections.

  5. Transcriptome Analysis of Syringa oblata Lindl. Inflorescence Identifies Genes Associated with Pigment Biosynthesis and Scent Metabolism.

    Directory of Open Access Journals (Sweden)

    Jian Zheng

    Full Text Available Syringa oblata Lindl. is a woody ornamental plant with high economic value and characteristics that include early flowering, multiple flower colors, and strong fragrance. Despite a long history of cultivation, the genetics and molecular biology of S. oblata are poorly understood. Transcriptome and expression profiling data are needed to identify genes and to better understand the biological mechanisms of floral pigments and scents in this species. Nine cDNA libraries were obtained from three replicates of three developmental stages: inflorescence with enlarged flower buds not protruded, inflorescence with corolla lobes not displayed, and inflorescence with flowers fully opened and emitting strong fragrance. Using the Illumina RNA-Seq technique, 319,425,972 clean reads were obtained and were assembled into 104,691 final unigenes (average length of 853 bp, 41.75% of which were annotated in the NCBI non-redundant protein database. Among the annotated unigenes, 36,967 were assigned to gene ontology categories and 19,956 were assigned to eukaryoticorthologous groups. Using the Kyoto Encyclopedia of Genes and Genomes pathway database, 12,388 unigenes were sorted into 286 pathways. Based on these transcriptomic data, we obtained a large number of candidate genes that were differentially expressed at different flower stages and that were related to floral pigment biosynthesis and fragrance metabolism. This comprehensive transcriptomic analysis provides fundamental information on the genes and pathways involved in flower secondary metabolism and development in S. oblata, providing a useful database for further research on S. oblata and other plants of genus Syringa.

  6. An in vitro cord formation assay identifies unique vascular phenotypes associated with angiogenic growth factors.

    Directory of Open Access Journals (Sweden)

    Beverly L Falcon

    Full Text Available Vascular endothelial growth factor (VEGF plays a dominant role in angiogenesis. While inhibitors of the VEGF pathway are approved for the treatment of a number of tumor types, the effectiveness is limited and evasive resistance is common. One mechanism of evasive resistance to inhibition of the VEGF pathway is upregulation of other pro-angiogenic factors such as fibroblast growth factor (FGF and epidermal growth factor (EGF. Numerous in vitro assays examine angiogenesis, but many of these assays are performed in media or matrix with multiple growth factors or are driven by VEGF. In order to study angiogenesis driven by other growth factors, we developed a basal medium to use on a co-culture cord formation system of adipose derived stem cells (ADSCs and endothelial colony forming cells (ECFCs. We found that cord formation driven by different angiogenic factors led to unique phenotypes that could be differentiated and combination studies indicate dominant phenotypes elicited by some growth factors. VEGF-driven cords were highly covered by smooth muscle actin, and bFGF-driven cords had thicker nodes, while EGF-driven cords were highly branched. Multiparametric analysis indicated that when combined EGF has a dominant phenotype. In addition, because this assay system is run in minimal medium, potential proangiogenic molecules can be screened. Using this assay we identified an inhibitor that promoted cord formation, which was translated into in vivo tumor models. Together this study illustrates the unique roles of multiple anti-angiogenic agents, which may lead to improvements in therapeutic angiogenesis efforts and better rational for anti-angiogenic therapy.

  7. Identifying resistance gene analogs associated with resistances to different pathogens in common bean.

    Science.gov (United States)

    López, Camilo E; Acosta, Iván F; Jara, Carlos; Pedraza, Fabio; Gaitán-Solís, Eliana; Gallego, Gerardo; Beebe, Steve; Tohme, Joe

    2003-01-01

    ABSTRACT A polymerase chain reaction approach using degenerate primers that targeted the conserved domains of cloned plant disease resistance genes (R genes) was used to isolate a set of 15 resistance gene analogs (RGAs) from common bean (Phaseolus vulgaris). Eight different classes of RGAs were obtained from nucleotide binding site (NBS)-based primers and seven from not previously described Toll/Interleukin-1 receptor-like (TIR)-based primers. Putative amino acid sequences of RGAs were significantly similar to R genes and contained additional conserved motifs. The NBS-type RGAs were classified in two subgroups according to the expected final residue in the kinase-2 motif. Eleven RGAs were mapped at 19 loci on eight linkage groups of the common bean genetic map constructed at Centro Internacional de Agricultura Tropical. Genetic linkage was shown for eight RGAs with partial resistance to anthracnose, angular leaf spot (ALS) and Bean golden yellow mosaic virus (BGYMV). RGA1 and RGA2 were associated with resistance loci to anthracnose and BGYMV and were part of two clusters of R genes previously described. A new major cluster was detected by RGA7 and explained up to 63.9% of resistance to ALS and has a putative contribution to anthracnose resistance. These results show the usefulness of RGAs as candidate genes to detect and eventually isolate numerous R genes in common bean.

  8. Institutional point-of-care glucometer identifies population trends in blood glucose associated with war.

    Science.gov (United States)

    Boaz, Mona; Matas, Zipora; Chaimy, Tova; Landau, Zohar; Bar Dayan, Yosefa; Berlovitz, Yitzhak; Wainstein, Julio

    2013-11-01

    Acute physiological stress has been shown to impair glucose homeostasis. War is a period of acute psychological stress, and its effect on glucose control is unknown. In this study random point-of-care (POC) glucose levels were measured using an automated, institutional glucometer in hospitalized adult patients prior to versus during the Israeli Pillar of Defense campaign (November 7-10, 2012). Random POC glucose values measured with the institutional blood glucose monitoring system were obtained 1 week prior to the Pillar of Defense campaign (November 7-10, 2012) and compared with values to those obtained during the first 4 days of the war (November 14-17, 2012). In total, 3,573 POC glucose measures were included: 1,865 during the pre-war period and 1,708 during the campaign. POC glucose measures were significantly higher during the war compared with the week preceding the war: 9.7±4.7 versus 9.3±4.2 mmol/L (P=0.02). In a general linear model, period (pre-war vs. during war) persisted as a significant predictor of POC glucose even after controlling for age, sex, and department type (internal medicine vs. surgical). Acute stress, such as a wartime situation, is associated with a significant increase in random blood glucose values in a population of hospitalized adults. Long-term follow-up of the individuals hospitalized during these two periods can reveal differences in morbidity and mortality trends.

  9. Nucleosome Density ChIP-Seq Identifies Distinct Chromatin Modification Signatures Associated with MNase Accessibility.

    Science.gov (United States)

    Lorzadeh, Alireza; Bilenky, Misha; Hammond, Colin; Knapp, David J H F; Li, Luolan; Miller, Paul H; Carles, Annaick; Heravi-Moussavi, Alireza; Gakkhar, Sitanshu; Moksa, Michelle; Eaves, Connie J; Hirst, Martin

    2016-11-15

    Nucleosome position, density, and post-translational modification are widely accepted components of mechanisms regulating DNA transcription but still incompletely understood. We present a modified native ChIP-seq method combined with an analytical framework that allows MNase accessibility to be integrated with histone modification profiles. Application of this methodology to the primitive (CD34+) subset of normal human cord blood cells enabled genomic regions enriched in one versus two nucleosomes marked by histone 3 lysine 4 trimethylation (H3K4me3) and/or histone 3 lysine 27 trimethylation (H3K27me3) to be associated with their transcriptional and DNA methylation states. From this analysis, we defined four classes of promoter-specific profiles and demonstrated that a majority of bivalent marked promoters are heterogeneously marked at a single-cell level in this primitive cell type. Interestingly, extension of this approach to human embryonic stem cells revealed an altered relationship between chromatin modification state and nucleosome content at promoters, suggesting developmental stage-specific organization of histone methylation states. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours.

    Directory of Open Access Journals (Sweden)

    Maja L Arendt

    2015-11-01

    Full Text Available Canine mast cell tumours (CMCT are one of the most common skin tumours in dogs with a major impact on canine health. Certain breeds have a higher risk of developing mast cell tumours, suggesting that underlying predisposing germ-line genetic factors play a role in the development of this disease. The genetic risk factors are largely unknown, although somatic mutations in the oncogene C-KIT have been detected in a proportion of CMCT, making CMCT a comparative model for mastocytosis in humans where C-KIT mutations are frequent. We have performed a genome wide association study in golden retrievers from two continents and identified separate regions in the genome associated with risk of CMCT in the two populations. Sequence capture of associated regions and subsequent fine mapping in a larger cohort of dogs identified a SNP associated with development of CMCT in the GNAI2 gene (p = 2.2x10-16, introducing an alternative splice form of this gene resulting in a truncated protein. In addition, disease associated haplotypes harbouring the hyaluronidase genes HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14 were identified as separate risk factors in European and US golden retrievers, respectively, suggesting that turnover of hyaluronan plays an important role in the development of CMCT.

  11. Newborn Dried Blood Spot Polymerase Chain Reaction to Identify Infants with Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss.

    Science.gov (United States)

    Ross, Shannon A; Ahmed, Amina; Palmer, April L; Michaels, Marian G; Sánchez, Pablo J; Stewart, Audra; Bernstein, David I; Feja, Kristina; Fowler, Karen B; Boppana, Suresh B

    2017-05-01

    To determine the utility of dried blood spot (DBS) polymerase chain reaction (PCR) in identifying infants with cytomegalovirus (CMV) infection-associated sensorineural hearing loss (SNHL). Newborns at 7 US hospitals between March 2007 and March 2012 were screened for CMV by saliva rapid culture and/or PCR. Infected infants were monitored for SNHL during the first 4 years of life to determine sensitivity, specificity, and positive and negative likelihood ratios of DBS PCR for identifying CMV-associated SNHL. DBS at birth was positive in 11 of 26 children (42%) with SNHL at age 4 years and in 72 of 270 children (27%) with normal hearing (P = .11). The sensitivity (42.3%; 95% CI, 23.4%-63.1%) and specificity (73.3%; 95% CI, 67.6%-78.5%) was low for DBS PCR in identifying children with SNHL at age 4 years. The positive and negative likelihood ratios of DBS PCR positivity to detect CMV-associated SNHL at age 4 years were 1.6 (95% CI, 0.97-2.6) and 0.8 (95% CI, 0.6-1.1), respectively. There was no difference in DBS viral loads between children with SNHL and those without SNHL. DBS PCR for CMV has low sensitivity and specificity for identifying infants with CMV-associated hearing loss. These findings, together with previous reports, demonstrate that DBS PCR does not identify either the majority of CMV-infected newborns or those with CMV-associated SNHL early in life. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 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