WorldWideScience

Sample records for association study ewas

  1. Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci.

    Science.gov (United States)

    Demerath, Ellen W; Guan, Weihua; Grove, Megan L; Aslibekyan, Stella; Mendelson, Michael; Zhou, Yi-Hui; Hedman, Åsa K; Sandling, Johanna K; Li, Li-An; Irvin, Marguerite R; Zhi, Degui; Deloukas, Panos; Liang, Liming; Liu, Chunyu; Bressler, Jan; Spector, Tim D; North, Kari; Li, Yun; Absher, Devin M; Levy, Daniel; Arnett, Donna K; Fornage, Myriam; Pankow, James S; Boerwinkle, Eric

    2015-08-01

    Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Karakterisering van het Etimologiewoordeboek van Afrikaans (EWA

    Directory of Open Access Journals (Sweden)

    Fons Moerdijk

    2011-10-01

    Full Text Available

    Samenvatting: Zesendertig jaar na Afrikaanse etimologieë van Boshoff en Nienaber verscheener in 2003 een nieuw etymologisch woordenboek van het Afrikaans: het Etimologiewoordeboek vanAfrikaans (EWA. Tussen die twee woordenboeken bestaat een wezenlijk verschil. Het werk vanBoshoff en Nienaber is vrijwel alleen toegankelijk voor specialisten en niet specifiek bedoeld vooreen breed publiek. EWA is juist allereerst bestemd voor de leek die zich interesseert voor de oorsprongen de geschiedenis van de eigen taal. Daarnaast biedt het ook de etymoloog en historischtaalkundige een hoop gegevens en inspiratie voor nader onderzoek. Als etymologisch woordenboekbezit EWA een aantal bijzondere, eigen kenmerken. De selectie van de woorden is bepaalddoor het beoogde gebruikerspubliek. Als gevolg daarvan bevat EWA verscheidene typen woordendie in traditionele etymologische woordenboeken doorgaans veronachtzaamd worden, zoals afleidingen,samenstellingen, neologismen en gemeenzame spreektaalwoorden. De artikelstructuurwordt gekenmerkt door een hoge graad van uniformiteit en consistentie. Het accent ligt op dezogenaamde etymologia proxima, de etymologie waarbij men één stap teruggaat en de meestdirecte herkomst van het woord biedt. Voorts is speciale aandacht besteed aan polysemie: nietalleen de herkomst van de dominante betekenis van een woord wordt gegeven, maar ook die vanzijn eventuele andere betekenis(sen. Benoemingsmotieven komen ook veelvuldig aan bod. In eeneventuele tweede druk zouden opvallende verschillen in vorm of betekenis altijd verklaard of inieder geval besproken moeten worden. Dat blijft nu nogal eens achterwege. Ook zou voorafgaandaan zo'n volgende editie meer onderzoek naar woordhistorisch materiaal uit primaire bronnenvoor met name de 17de–19de eeuw verricht moeten worden. Het zou mooi zijn als deze eersteuitgave van EWA de aanleiding tot een dergelijk onderzoek zou vormen.

    Sleutelwoorden: BENOEMINGSMOTIEF, ETYMOLOGIA PROXIMA

  3. Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution.

    Science.gov (United States)

    van Iterson, Maarten; van Zwet, Erik W; Heijmans, Bastiaan T

    2017-01-27

    We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking.

  4. Karakterisering van het "Etimologiewoordeboek van Afrikaans" (EWA)

    African Journals Online (AJOL)

    Zesendertig jaar na Afrikaanse etimologieë van Boshoff en Nienaber verscheen er in 2003 een nieuw etymologisch woordenboek van het Afrikaans: het Etimologiewoordeboek van Afrikaans (EWA). Tussen die twee woordenboeken bestaat een wezenlijk verschil. Het werk van Boshoff en Nienaber is vrijwel alleen ...

  5. Measuring surface-water loss in Honouliuli Stream near the ‘Ewa Shaft, O‘ahu, Hawai‘i

    Science.gov (United States)

    Rosa, Sarah N.

    2017-05-30

    The Honolulu Board of Water Supply is currently concerned with the possibility of bacteria in the pumped water of the ‘Ewa Shaft (State well 3-2202-21). Groundwater from the ‘Ewa Shaft could potentially be used to meet future potable water needs in the ‘Ewa area on the island of O‘ahu. The source of the bacteria in the pumped water is unknown, although previous studies indicate that surface water may be lost to the subsurface near the site. The ‘Ewa Shaft consists of a vertical shaft, started near the south bank of Honouliuli Stream at an altitude of about 161 feet, and two horizontal infiltration tunnels near sea level. The shaft extracts groundwater from near the top of the freshwater lens in the Waipahu-Waiawa aquifer system within the greater Pearl Harbor Aquifer Sector, a designated Water Management Area.The surface-water losses were evaluated with continuous groundwater-level data from the ‘Ewa Shaft and a nearby monitoring well, continuous stream-discharge data from U.S. Geological Survey streamflow-gaging station 16212490 (Honouliuli Stream at H-1 Freeway near Waipahu), and seepage-run measurements in Honouliuli Stream and its tributary. During storms, discharge at the Honouliuli Stream gaging station increases and groundwater levels at ‘Ewa Shaft and a nearby monitoring well also increase. The concurrent increase in water levels at ‘Ewa Shaft and the nearby monitoring well during storms indicates that regional groundwater-level changes related to increased recharge, reduced withdrawals (due to a decrease in demand during periods of rainfall), or both may be occurring; although these data do not preclude the possibility of local recharge from Honouliuli Stream. Discharge measurements from two seepage runs indicate that surface water in the immediate area adjacent to ‘Ewa Shaft infiltrates into the streambed and may later reach the groundwater system developed by the ‘Ewa Shaft. The estimated seepage loss rates in the vicinity of ‘Ewa

  6. 1.0. B. Ewa

    African Journals Online (AJOL)

    ustic moisture regime of the West African savanna soil belt (Miller and Donahue, 1997). They are characterized by hard concretions as a result of residual accumulations of hematite. (Fe203) consolidated with clay (Kaolinite-. AlZSiZOJOHL, K-Feldspar - KAlSi3Og) and remain in association with other minerals of the soils.

  7. Karakterisering van het Etimologie- woordeboek van Afrikaans (EWA)

    African Journals Online (AJOL)

    rbr

    Abstract: Characterisation of the Etimologiewoordeboek van Afrikaans (EWA). In 2003, thirty six years after Afrikaanse etimologieë by Boshoff and Nienaber, a new etymological dictionary of Afrikaans has been published: the Etimologiewoordeboek van Afrikaans (EWA). There is a substantial difference between these two ...

  8. Ewa Toniak, Olbrzymki. Kobiety i socrealizm

    Directory of Open Access Journals (Sweden)

    Wojciech Tomasik

    2009-02-01

    Full Text Available Dans Olbrzymki. Kobiety i socrealizm (Les Géantes. Les femmes et le réalisme socialiste, Ewa Toniak se base sur le constat que l’art polonais de la période réaliste socialiste propose une sorte de discours classique et patriarcal. L’attention de l’auteur est focalisée sur l’image de la femme, telle qu’elle apparaît dans des réalisations artistiques (peintures, sculptures, films documentaires et de fiction, œuvres littéraires et couvertures de magazines des années 1950 et à travers le récit ...

  9. EWA Selection Strategy with Channel Handoff Scheme in Cognitive Radio

    National Research Council Canada - National Science Library

    Sun Yong; Qian Jiansheng

    2014-01-01

      This paper proposes an improved Experience-Weighted Attraction (EWA) selection algorithm with channel handoff scheme in order to meet the practical requirement for Cognitive Radio (CR) application...

  10. Karakterisering van het Etimologie- woordeboek van Afrikaans (EWA)

    African Journals Online (AJOL)

    rbr

    Samenvatting: Zesendertig jaar na Afrikaanse etimologieë van Boshoff en Nienaber verscheen er in 2003 een nieuw etymologisch woordenboek van het Afrikaans: het Etimologiewoordeboek van. Afrikaans (EWA). Tussen die twee woordenboeken bestaat een wezenlijk verschil. Het werk van. Boshoff en Nienaber is ...

  11. Epigenome-wide association of DNA methylation in whole blood with bone mineral density

    OpenAIRE

    John A. Morris; Tsai, Pei‐Chien; Joehanes, Roby; Zheng, Jie; Trajanoska, Katerina; Soerensen, Mette; Forgetta, Vincenzo; Castillo‐Fernandez, Juan Edgar; Frost, Morten; Spector, Tim D.; Christensen, Kaare; Christiansen, Lene; Rivadeneira, Fernando; Tobias, Jonathan H.; Evans, David M.

    2017-01-01

    Genetic and environmental determinants of skeletal phenotypes such as bone mineral density (BMD) may converge through the epigenome, providing a tool to better understand osteoporosis pathophysiology. As the epigenetics of BMD have been largely unexplored in humans, we performed an epigenome wide association study (EWAS) of BMD. We undertook a large-scale BMD EWAS using the Infinium HumanMethylation450 array to measure site-specific DNA methylation in up to 5,515 European descent individuals ...

  12. Longitudinal exome-wide association study to identify genetic susceptibility loci for hypertension in a Japanese population.

    Science.gov (United States)

    Yasukochi, Yoshiki; Sakuma, Jun; Takeuchi, Ichiro; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Yamada, Yoshiji

    2017-12-08

    Genome-wide association studies have identified various genetic variants associated with complex disorders. However, these studies have commonly been conducted in a cross-sectional manner. Therefore, we performed a longitudinal exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify genetic variants that confer susceptibility to hypertension using ~244 000 single-nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals who underwent annual health check-ups for several years. After quality control, the association of hypertension with SNVs was tested using a generalized estimating equation model. Finally, our longitudinal EWAS detected seven hypertension-related SNVs that passed strict criteria. Among these variants, six SNVs were densely located at 12q24.1, and an East Asian-specific motif (haplotype) 'CAAAA' comprising five derived alleles was identified. Statistical analyses showed that the prevalence of hypertension in individuals with the East Asian-specific haplotype was significantly lower than that in individuals with the common haplotype 'TGGGT'. Furthermore, individuals with the East Asian haplotype may be less susceptible to the adverse effects of smoking on hypertension. The longitudinal EWAS for the recessive model showed that a novel SNV, rs11917356 of COL6A5, was significantly associated with systolic blood pressure, and the derived allele at the SNV may have spread throughout East Asia in recent evolutionary time.

  13. Epigenome-Wide Association Study of Aggressive Behavior.

    Science.gov (United States)

    van Dongen, Jenny; Nivard, Michel G; Baselmans, Bart M L; Zilhão, Nuno R; Ligthart, Lannie; Heijmans, Bastiaan T; Bartels, Meike; Boomsma, Dorret I

    2015-12-01

    Aggressive behavior is highly heritable, while environmental influences, particularly early in life, are also important. Epigenetic mechanisms, such as DNA methylation, regulate gene expression throughout development and adulthood, and may mediate genetic and environmental effects on complex traits. We performed an epigenome-wide association study (EWAS) to identify regions in the genome where DNA methylation level is associated with aggressive behavior. Subjects took part in longitudinal survey studies from the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2004 and 2011 (N = 2,029, mean age at blood sampling = 36.4 years, SD = 12.4, females = 69.2%). Aggressive behavior was rated with the ASEBA Adult Self-Report (ASR). DNA methylation was measured in whole blood by the Illumina HM450k array. The association between aggressive behavior and DNA methylation level at 411,169 autosomal sites was tested. Association analyses in the entire cohort showed top sites at cg01792876 (chr8; 116,684,801, nearest gene = TRPS1, p = 7.6 × 10(-7), False discovery rate (FDR) = 0.18) and cg06092953 (chr18; 77,905,699, nearest gene = PARD6G-AS1, p = 9.0 ×10(-7), FDR = 0.18). Next, we compared methylation levels in 20 pairs of monozygotic (MZ) twins highly discordant for aggression. Here the top sites were cg21557159 (chr 11; 107,795,699, nearest gene = RAB39, p = 5.7 × 10(-6), FDR = 0.99), cg08648367 (chr 19; 51,925,472, nearest gene = SIGLEC10, p = 7.6 × 10(-6), FDR = 0.99), and cg14212412 (chr 6; 105,918,992, nearest gene = PREP, p = 8.0 × 10(-6), FDR = 0.99). The two top hits based on the entire cohort showed the same direction of effect in discordant MZ pairs (cg01792876, P(discordant twins) = 0.09 and cg06092953, P(discordant twins) = 0.24). The other way around, two of the three most significant sites in discordant MZ pairs showed the same direction of effect in the entire cohort (cg08648367, P(entire EWAS) = 0.59 and cg14212412, P

  14. Increased correlation between methylation sites in epigenome-wide replication studies: impact on analysis and results.

    Science.gov (United States)

    Popovic, Maja; Fasanelli, Francesca; Fiano, Valentina; Biggeri, Annibale; Richiardi, Lorenzo

    2017-11-06

    To show that an increased correlation between CpGs after selection through an epigenome-wide association studies (EWAS) might translate into biased replication results. Pairwise correlation coefficients between CpGs selected in two published EWAS, the top hits replication, Bonferroni p-values, Benjamini-Hochberg (BH) false discovery rate (FDR) and directional FDR r-values were calculated in the NINFEA cohort data. Exposures' random permutations were performed to show the empirical p-value distributions. The average pairwise correlation coefficients between CpGs were enhanced after selection for the replication (e.g., from 0.12 at genome-wide level to 0.26 among the selected CpGs), affecting the empirical p-value distributions and the usual multiple testing control. Bonferroni and Benjamini-Hochberg FDR are inappropriate for the EWAS replication phase, and methods that account for the underlying correlation need to be used.

  15. The abundance and composition of crabs (Decapoda) in Uta Ewa ...

    African Journals Online (AJOL)

    ... abundant accounting for 46.6% of the percentage abundance. Station 2 had the highest Shannon diversity index of 1.22, while Station 1 had 1.15. The abundance and composition of crab species in the study areas is an indication that the area is an important ecological zone for benthos macroinvertebrates conservation.

  16. A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies.

    Science.gov (United States)

    Teschendorff, Andrew E; Breeze, Charles E; Zheng, Shijie C; Beck, Stephan

    2017-02-13

    Intra-sample cellular heterogeneity presents numerous challenges to the identification of biomarkers in large Epigenome-Wide Association Studies (EWAS). While a number of reference-based deconvolution algorithms have emerged, their potential remains underexplored and a comparative evaluation of these algorithms beyond tissues such as blood is still lacking. Here we present a novel framework for reference-based inference, which leverages cell-type specific DNAse Hypersensitive Site (DHS) information from the NIH Epigenomics Roadmap to construct an improved reference DNA methylation database. We show that this leads to a marginal but statistically significant improvement of cell-count estimates in whole blood as well as in mixtures involving epithelial cell-types. Using this framework we compare a widely used state-of-the-art reference-based algorithm (called constrained projection) to two non-constrained approaches including CIBERSORT and a method based on robust partial correlations. We conclude that the widely-used constrained projection technique may not always be optimal. Instead, we find that the method based on robust partial correlations is generally more robust across a range of different tissue types and for realistic noise levels. We call the combined algorithm which uses DHS data and robust partial correlations for inference, EpiDISH (Epigenetic Dissection of Intra-Sample Heterogeneity). Finally, we demonstrate the added value of EpiDISH in an EWAS of smoking. Estimating cell-type fractions and subsequent inference in EWAS may benefit from the use of non-constrained reference-based cell-type deconvolution methods.

  17. Epigenome-Wide Association Study of Wellbeing.

    Science.gov (United States)

    Baselmans, Bart M L; van Dongen, Jenny; Nivard, Michel G; Lin, Bochao D; Zilhão, Nuno R; Boomsma, Dorret I; Bartels, Meike

    2015-12-01

    Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10(-8) and cg01940273, p = 2.34 * 10(-8)) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10(-7); cg09716613, p = 3.23 * 10(-7); cg04387347, p = 3.95 * 10(-7); and cg02290168, p = 5.23 * 10(-7)) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.

  18. Uncertainty in vertical extrapolation of wind statistics: shear-exponent and WAsP/EWA methods

    DEFF Research Database (Denmark)

    Kelly, Mark C.

    for uncertainties inherent in determination of (wind) shear exponents, and subsequent vertical extrapolation of wind speeds. The report further outlines application of the theory and results of Kelly & Troen (2014-6) for gauging the uncertainty inherent in use of the European Wind Atlas (EWA) / WAsP method......This report provides formulations for estimation of uncertainties involved in vertical extrapolation of winds, as well as the total uncertainty incurred when winds observed at one height are extrapolated to turbine hub height for wind resource assessment. This includes new derivations....../푧obs); for larger extrapolations, WAsP-based extrapolation leads to smaller estimated uncertainties than the shear-extrapolation method.A primary motivation for—and part of—this work is the creation of a standard for uncertainty estimation and reporting, which is known as the IEC61400-15. The author is actively...

  19. Fish Census Data from Annual Surveys at Selected Shallow-water Sites Near the Barber's Point Sewage Outfall, Ewa, Oahu, Hawaii, 1991 - 2010 (NODC Accession 0073346)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Honouliuli Wastewater Treatment Plant (WWTP) located in Ewa, Oahu, Hawaii, near Barbers Point (Kalaeloa) has been in operation since 1982. It releases...

  20. Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins

    DEFF Research Database (Denmark)

    Starnawska, Anna; Tan, Qihua; McGue, Matt

    2017-01-01

    As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenance......, and synaptic plasticity. Using the twin design we performed an epigenome-wide association study (EWAS) in a population of 486 middle-aged monozygotic twins (mean age at follow-up 65.9, SD = 6.1) and correlated their blood DNA methylation to their level (cross-sectional analysis) and change in cognitive...... abilities over 10 years (longitudinal analysis). We identified several CpG sites where cross-sectional cognitive functioning was associated with DNA methylation levels. The top identified loci were located in ZBTB46 (p = 5.84 × 10-7), and TAF12 (p = 4.91 × 10-7). KEGG's enrichment analyses of the most...

  1. A Comparative Study of Five Association Tests Based on CpG Set for Epigenome-Wide Association Studies.

    Directory of Open Access Journals (Sweden)

    Qiuyi Zhang

    Full Text Available An epigenome-wide association study (EWAS is a large-scale study of human disease-associated epigenetic variation, specifically variation in DNA methylation. High throughput technologies enable simultaneous epigenetic profiling of DNA methylation at hundreds of thousands of CpGs across the genome. The clustering of correlated DNA methylation at CpGs is reportedly similar to that of linkage-disequilibrium (LD correlation in genetic single nucleotide polymorphisms (SNP variation. However, current analysis methods, such as the t-test and rank-sum test, may be underpowered to detect differentially methylated markers. We propose to test the association between the outcome (e.g case or control and a set of CpG sites jointly. Here, we compared the performance of five CpG set analysis approaches: principal component analysis (PCA, supervised principal component analysis (SPCA, kernel principal component analysis (KPCA, sequence kernel association test (SKAT, and sliced inverse regression (SIR with Hotelling's T2 test and t-test using Bonferroni correction. The simulation results revealed that the first six methods can control the type I error at the significance level, while the t-test is conservative. SPCA and SKAT performed better than other approaches when the correlation among CpG sites was strong. For illustration, these methods were also applied to a real methylation dataset.

  2. A simulation study on power of epigenome-wide association analysis using disease-discordant twin design

    DEFF Research Database (Denmark)

    Li, Weilong; Baumbach, Jan; Christiansen, Lene

    Background Identical twin pairs discordant for a disease have been widely used in epigenome-wide association studies (EWAS) of complex diseases because the underlying genetic background is cancelled out. Although the twin design is deemed to have enriched power as compared with ordinary case......-control design, its statistical power has not been well investigated. Methods We perform a computer simulation study on the power of the disease discordant twin design assuming that both genetic and environmental factors contribute to the liability of a disease phenotype. Power is assessed under different levels...... with moderate effect and for diseases with heritability>0.3. The power advantage in discordant twin design becomes more obvious with increasing heritability. For diseases with no genetic background, the twin design is slightly underpowered, while for high heritability (0.5), high intrapair methylation...

  3. Ewa Korzeniowska as a mother and a good spirit of the home – the upbringing of children in a Polish Borderland noble family during the partitions [Ewa Korzeniowska jako matka – strażniczka ogniska domowego. Wychowanie w kresowej rodzinie szlacheckiej na ziemiach polskich pod zaborami w okresie międzypowstaniowym

    Directory of Open Access Journals (Sweden)

    Joanna SKOLIK

    2017-11-01

    Full Text Available The article presents a portrait of Ewa Korzeniowska; Joseph Conrad’s mother and Tadeusz Bobrowski’s sister. Her life was seriously influenced by Russian autocracy persecuting those Poles who even dared to dream about an independent Poland. Her letters and the recollections of other family members present her as a true Polish mother and wife.

  4. New Nordic Exceptionalism: Jeuno JE Kim and Ewa Einhorn's The United Nations of Norden and other realist utopias

    Directory of Open Access Journals (Sweden)

    Mathias Danbolt

    2016-11-01

    Full Text Available At the 2009 Nordic Culture Forum summit in Berlin that centered on the profiling and branding of the Nordic region in a globalized world, one presenter stood out from the crowd. The lobbyist Annika Sigurdardottir delivered a speech that called for the establishment of “The United Nations of Norden”: A Nordic union that would gather the nations and restore Norden's role as the “moral superpower of the world.” Sigurdardottir's presentation generated such a heated debate that the organizers had to intervene and reveal that the speech was a performance made by the artists Jeuno JE Kim and Ewa Einhorn. This article takes Kim and Einhorn's intervention as a starting point for a critical discussion of the history and politics of Nordic image-building. The article suggests that the reason Kim and Einhorn's speech passed as a serious proposal was due to its meticulous mimicking of two discursive formations that have been central to the debates on the branding of Nordicity over the last decades: on the one hand, the discourse of “Nordic exceptionalism,” that since the 1960s has been central to the promotion of a Nordic political, socio-economic, and internationalist “third way” model, and, on the other hand, the discourse on the “New Nordic,” that emerged out of the New Nordic Food-movement in the early 2000s, and which has given art and culture a privileged role in the international re-fashioning of the Nordic brand. Through an analysis of Kim and Einhorn's United Nations of Norden (UNN-performance, the article examines the historical development and ideological underpinnings of the image of Nordic unity at play in the discourses of Nordic exceptionalism and the New Nordic. By focusing on how the UNN-project puts pressure on the role of utopian imaginaries in the construction of Nordic self-images, the article describes the emergence of a discursive framework of New Nordic Exceptionalism.

  5. Epigenome-Wide Association Study of Cognitive Functioning in Middle-Aged Monozygotic Twins

    Directory of Open Access Journals (Sweden)

    Anna Starnawska

    2017-12-01

    Full Text Available As the world's population ages, the age-related cognitive decline presents a great challenge to world's healthcare systems. One of the molecular mechanisms implicated in cognitive ageing is DNA methylation, an epigenetic modification known to be a key player in memory formation, maintenance, and synaptic plasticity. Using the twin design we performed an epigenome-wide association study (EWAS in a population of 486 middle-aged monozygotic twins (mean age at follow-up 65.9, SD = 6.1 and correlated their blood DNA methylation to their level (cross-sectional analysis and change in cognitive abilities over 10 years (longitudinal analysis. We identified several CpG sites where cross-sectional cognitive functioning was associated with DNA methylation levels. The top identified loci were located in ZBTB46 (p = 5.84 × 10−7, and TAF12 (p = 4.91 × 10−7. KEGG's enrichment analyses of the most associated findings identified “Neuroactive ligand-receptor interaction” as the most enriched pathway (p = 0.0098. Change in cognitive functioning over 10 years was associated with DNA methylation levels in AGBL4 (p = 9.01 × 10−7 and SORBS1 (p = 5.28 × 10−6, with the first gene playing an important role in neuronal survival and the latter gene implicated before in Alzheimer's disease and ischemic stroke. Our findings point to an association between changes in DNA methylation of genes related to neuronal survival and change of cognitive functioning in aging individuals.

  6. Sharing Water with Nature: Insights on Environmental Water Allocation from a Case Study of the Murrumbidgee Catchment, Australia

    Directory of Open Access Journals (Sweden)

    Becky Swainson

    2011-02-01

    Full Text Available Human use of freshwater resources has placed enormous stress on aquatic ecosystems in many regions of the world. At one time, this was considered an acceptable price to pay for economic growth and development. Nowadays, however, many societies are seeking a better balance between healthy aquatic ecosystems and viable economies. Unfortunately, historically, water allocation systems have privileged human uses over the environment. Thus, jurisdictions seeking to ensure that adequate water is available for the environment must typically deal with the fact that economies and communities have become dependent on water. Additionally, they must often layer institutions for environmental water allocation (EWA on top of already complex institutional systems. This paper explores EWA in a jurisdiction – New South Wales (NSW, Australia – where water scarcity has become a priority. Using an in-depth case study of EWA in the Murrumbidgee catchment, NSW, we characterise the NSW approach to EWA with the goal of highlighting the myriad challenges encountered in EWA planning and implementation. Sharing water between people and the environment, we conclude, is much more than just a scientific and technical challenge. EWA in water-scarce regions involves reshaping regional economies and societies. Thus, political and socio-economic considerations must be identified and accounted for from the outset of planning and decision-making processes.

  7. Genome-wide DNA methylation study in human placenta identifies novel loci associated with maternal smoking during pregnancy.

    Science.gov (United States)

    Morales, Eva; Vilahur, Nadia; Salas, Lucas A; Motta, Valeria; Fernandez, Mariana F; Murcia, Mario; Llop, Sabrina; Tardon, Adonina; Fernandez-Tardon, Guillermo; Santa-Marina, Loreto; Gallastegui, Mara; Bollati, Valentina; Estivill, Xavier; Olea, Nicolas; Sunyer, Jordi; Bustamante, Mariona

    2016-10-01

    We conducted an epigenome-wide association study (EWAS) of DNA methylation in placenta in relation to maternal tobacco smoking during pregnancy and examined whether smoking-induced changes lead to low birthweight. DNA methylation in placenta was measured using the Illumina HumanMethylation450 BeadChip in 179 participants from the INfancia y Medio Ambiente (INMA) birth cohort. Methylation levels across 431 311 CpGs were tested for differential methylation between smokers and non-smokers in pregnancy. We took forward three top-ranking loci for further validation and replication by bisulfite pyrosequencing using data of 248 additional participants of the INMA cohort. We examined the association of methylation at smoking-associated loci with birthweight by applying a mediation analysis and a two-sample Mendelian randomization approach. Fifty CpGs were differentially methylated in placenta between smokers and non-smokers during pregnancy [false discovery rate (FDR) < 0.05]. We validated and replicated differential methylation at three top-ranking loci: cg27402634 located between LINC00086 and LEKR1, a gene previously related to birthweight in genome-wide association studies; cg20340720 (WBP1L); and cg25585967 and cg12294026 (TRIO). Dose-response relationships with maternal urine cotinine concentration during pregnancy were confirmed. Differential methylation at cg27402634 explained up to 36% of the lower birthweight in the offspring of smokers (Sobel P-value < 0.05). A two-sample Mendelian randomization analysis provided evidence that decreases in methylation levels at cg27402634 lead to decreases in birthweight. We identified novel loci differentially methylated in placenta in relation to maternal smoking during pregnancy. Adverse effects of maternal smoking on birthweight of the offspring may be mediated by alterations in the placental methylome. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International

  8. Differentially methylated DNA regions in monozygotic twin pairs discordant for rheumatoid arthritis.An epigenome - wide study.

    Directory of Open Access Journals (Sweden)

    Anders Jørgen Svendsen

    2016-11-01

    Full Text Available Objectives: In an explorative epigenome-wide association study (EWAS to search for gene independent, differentially methylated DNA positions (DMPs and regions (DMRs associated with rheumatoid arthritis (RA by studying monozygotic (MZ twin pairs discordant for rheumatoid arthritis.Methods: Genomic DNA was isolated from whole blood samples from 28 monozygotic (MZ twin pairs discordant for RA. DNA methylation was measured using the HumanMethylation450 BeadChips. Smoking, anti-cyclic citrullinated peptide antibodies and immunosuppressive treatment were included as covariates. Pathway analysis was performed using GREAT.Results: Smoking was significantly associated with hypomethylation of a DMR overlapping the promoter region of the RNF5 and the AGPAT1, which are implicated in inflammation and autoimmunity, whereas DMARD treatment induced hypermethylation of the same region. Additionally, the promotor region of both S100A6 and EFCAB4B were hypomethylated and both genes have previously been associated with RA. We replicated several candidate genes identified in a previous EWAS in treatment naïve RA singletons. Gene set analysis indicated the involvement of immunologic signatures and cancer-related pathways in RA.Conclusion: We identified several differentially methylated regions associated with RA which may represent environmental effects or consequences of the disease and plausible biological pathways pertinent to the pathogenesis of rheumatoid arthritis

  9. Venous thromboembolism associated with protein S deficiency due ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 96; Issue 6. Venous thromboembolism associated with protein S deficiency due to Arg451∗ mutation in PROS1 gene: a case report and a literature review. EWA WYPASEK MAREK KARPINSKI MARTINE ALHENC-GELAS ANETTA UNDAS. REVIEW ARTICLE Volume 96 Issue ...

  10. The effects of storm-drains with periodic flows on intertidal algal assemblages in 'Ewa Beach (O'ahu), Hawai'i.

    Science.gov (United States)

    Cox, T E; Foster, M S

    2013-05-15

    Storm-water drainage systems have potential to collect and focus nutrient enriched runoff into coastal systems. Storm-drain effluent could support macroalgal production and result in altered communities. To test this hypothesis, we assessed species composition and percent cover of native and non-native benthic macroalgae at eight intertidal sites along 'Ewa Beach, Hawai'i. Three sites contain storm-drainage outlets (drain 16-52 acres) that deliver effluent into the intertidal zone whereas five sites were located ≥ 100 m away and served as comparisons to determine differences related to the presence of storm-water. Results revealed lush and diverse macroalgal assemblages, similar at all sites. Furthermore, the abundance of non-native species (Acanthophora spicifera, Hypnea musciformis) was not related to presence of storm-drains. The finding that macroalgal assemblages are not related to storm-waters is contrary to an earlier investigation in the same location and underscores the importance of sampling design and habitat variation when assessing impacts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. 1.0. B. Ewa

    African Journals Online (AJOL)

    Lanthanum Lit-140 487,1596.5 26.46(0.02). Lutetium Lu-177 208.4 0.59(0.01). Neodymium Nd-147 91,531 20.21(5.91). Potassium(%)K-42 1524.7 1.46(0,0]). Rubidium Rb—86 1076.6 71.66(2.11). 112.33Scandium Sc-46 889.3,1120.3. Sodium(%)Na-24 1368.5 0.01(1.0E-04). Tantalum Til—182 1221.4 2.12(0.07). Thorium ...

  12. 1.0. B. Ewa

    African Journals Online (AJOL)

    Europium Eu-152 1408 0.625(0.01). Hafnium Hf-181 482 35.41(0.41). 1ron(“/0) Fe-59 1099.2,1291.5 O.82(().01). Lanthanuin La-140 487,1596.5 26.46(0.02). Lutetium Lu-177 208.4 0.59(0.01). Neodymium Nd-147 91,531 20.21(5.91). Potassium(%)K-42 1524.7 1.46(0,01). Rubidium R1'J—86 1076.6 71.66(2.11).

  13. Medication-wide association studies

    NARCIS (Netherlands)

    P.B. Ryan (Patrick); D. Madigan (David); P.E. Stang (Paul); M.J. Schuemie (Martijn); G. Hripcsak (G.)

    2013-01-01

    textabstractUndiscovered side effects of drugs can have a profound effect on the health of the nation, and electronic health-care databases offer opportunities to speed up the discovery of these side effects. We applied a "medication-wide association study" approach that combined multivariate

  14. Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model.

    Science.gov (United States)

    Emeny, Rebecca T; Baumert, Jens; Zannas, Anthony S; Kunze, Sonja; Wahl, Simone; Iurato, Stella; Arloth, Janine; Erhardt, Angelika; Balsevich, Georgia; Schmidt, Mathias V; Weber, Peter; Kretschmer, Anja; Pfeiffer, Liliane; Kruse, Johannes; Strauch, Konstantin; Roden, Michael; Herder, Christian; Koenig, Wolfgang; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Binder, Elisabeth B; Ladwig, Karl-Heinz

    2018-01-01

    Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (β-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (β=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress

  15. eFORGE : A Tool for Identifying Cell Type-Specific Signal in Epigenomic Data

    NARCIS (Netherlands)

    Breeze, Charles E.; Paul, Dirk S.; van Dongen, Jenny; Butcher, Lee M.; Ambrose, John C.; Barrett, James E.; Lowe, Robert; Rakyan, Vardhman K.; Iotchkova, Valentina; Frontini, Mattia; Downes, Kate; Ouwehand, Willem H.; Laperle, Jonathan; Jacques, Pierre-ETienne; Bourque, Guillaume; Bergmann, Anke K.; Siebert, Reiner; Vellenga, Edo; Saeed, Sadia; Matarese, Filomena; Martens, Joost H. A.; Stunnenberg, Hendrik G.; Teschendorff, Andrew E.; Herrero, Javier; Birney, Ewan; Dunham, Ian; Beck, Stephan

    2016-01-01

    Epigenome-wide association studies (EWAS) provide an alternative approach for studying human disease through consideration of non-genetic variants such as altered DNA methylation. To advance the complex interpretation of EWAS, we developed eFORGE (http://eforge.cs.ucl.ac.uk/), a new stand-alone and

  16. SOCIAL PARTICIPATION IN THE ENVIRONMENTAL FLOW ASSESSMENT: THE SÃO FRANCISCO RIVER CASE STUDY

    Directory of Open Access Journals (Sweden)

    Yvonilde Dantas Pinto Medeiros

    2013-03-01

    Full Text Available Traditionally, water resource management has been developed using an essentially technical approach. Currently, public opinion on water resource management is formed as a result of growing environmental concerns and social conflicts arising from poorly planned actions. Environmental problems are complex and have multiple dimensions, including social and economic. Therefore, the inclusion of a human dimension in integrated assessment methodologies is required for the introduction of new elements to the water management planning process. Environmental water allocation (EWA is understood as the quantity, quality and distribution of water required for the maintenance of the functions and processes of aquatic ecosystems on which people depend. Within the various holistic assessment methodologies, the Building Block Methodology (BBM was found to be the most suitable, in the Brazilian context, for maintaining and restoring essential elements of the natural flow regime. This article describes the process of social participation in the environmental flow assessment (EFA for the Sao Francisco River, and compares it with some of the lessons learned from EFA in other parts of the world. The process involved multiple stakeholders who have conflicting interests. BBM was used to guide the field interviews, to incorporate the empirical observations by the local population and to guide the methodological procedures of the multidisciplinary team. The results of the study indicate the effectiveness of this holistic approach in organizing the elements to be evaluated. It also facilitated important contributions to the establishment of a dialogue between the actors to achieve a better understanding of the multiple aspects involved in the decisions associated with the EWA.

  17. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    Full Text Available Gene polymorphisms associated so far with body mass index (BMI can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05, and found positive associations between methylation and alanine aminotransferase (ALT levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007. These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD.

  18. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis.

    Directory of Open Access Journals (Sweden)

    Vardhman K Rakyan

    2011-09-01

    Full Text Available Monozygotic (MZ twin pair discordance for childhood-onset Type 1 Diabetes (T1D is ∼50%, implicating roles for genetic and non-genetic factors in the aetiology of this complex autoimmune disease. Although significant progress has been made in elucidating the genetics of T1D in recent years, the non-genetic component has remained poorly defined. We hypothesized that epigenetic variation could underlie some of the non-genetic component of T1D aetiology and, thus, performed an epigenome-wide association study (EWAS for this disease. We generated genome-wide DNA methylation profiles of purified CD14+ monocytes (an immune effector cell type relevant to T1D pathogenesis from 15 T1D-discordant MZ twin pairs. This identified 132 different CpG sites at which the direction of the intra-MZ pair DNA methylation difference significantly correlated with the diabetic state, i.e. T1D-associated methylation variable positions (T1D-MVPs. We confirmed these T1D-MVPs display statistically significant intra-MZ pair DNA methylation differences in the expected direction in an independent set of T1D-discordant MZ pairs (P = 0.035. Then, to establish the temporal origins of the T1D-MVPs, we generated two further genome-wide datasets and established that, when compared with controls, T1D-MVPs are enriched in singletons both before (P = 0.001 and at (P = 0.015 disease diagnosis, and also in singletons positive for diabetes-associated autoantibodies but disease-free even after 12 years follow-up (P = 0.0023. Combined, these results suggest that T1D-MVPs arise very early in the etiological process that leads to overt T1D. Our EWAS of T1D represents an important contribution toward understanding the etiological role of epigenetic variation in type 1 diabetes, and it is also the first systematic analysis of the temporal origins of disease-associated epigenetic variation for any human complex disease.

  19. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  20. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Study of obesity associated proopiomelanocortin gene polymorphism: Relation to metabolic profile and eating habits in a sample of obese Egyptian children and ... Polymorphisms in the POMC gene locus are associated with obesity phenotypes. Aim: To ... Keywords: Childhood obesity; POMC gene; Metabolic syndrome ...

  1. eFORGE: A Tool for Identifying Cell Type-Specific Signal in Epigenomic Data.

    Science.gov (United States)

    Breeze, Charles E; Paul, Dirk S; van Dongen, Jenny; Butcher, Lee M; Ambrose, John C; Barrett, James E; Lowe, Robert; Rakyan, Vardhman K; Iotchkova, Valentina; Frontini, Mattia; Downes, Kate; Ouwehand, Willem H; Laperle, Jonathan; Jacques, Pierre-Étienne; Bourque, Guillaume; Bergmann, Anke K; Siebert, Reiner; Vellenga, Edo; Saeed, Sadia; Matarese, Filomena; Martens, Joost H A; Stunnenberg, Hendrik G; Teschendorff, Andrew E; Herrero, Javier; Birney, Ewan; Dunham, Ian; Beck, Stephan

    2016-11-15

    Epigenome-wide association studies (EWAS) provide an alternative approach for studying human disease through consideration of non-genetic variants such as altered DNA methylation. To advance the complex interpretation of EWAS, we developed eFORGE (http://eforge.cs.ucl.ac.uk/), a new standalone and web-based tool for the analysis and interpretation of EWAS data. eFORGE determines the cell type-specific regulatory component of a set of EWAS-identified differentially methylated positions. This is achieved by detecting enrichment of overlap with DNase I hypersensitive sites across 454 samples (tissues, primary cell types, and cell lines) from the ENCODE, Roadmap Epigenomics, and BLUEPRINT projects. Application of eFORGE to 20 publicly available EWAS datasets identified disease-relevant cell types for several common diseases, a stem cell-like signature in cancer, and demonstrated the ability to detect cell-composition effects for EWAS performed on heterogeneous tissues. Our approach bridges the gap between large-scale epigenomics data and EWAS-derived target selection to yield insight into disease etiology. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Associative Visual Agnosia: A Case Study

    OpenAIRE

    A. Charnallet; Carbonnel, S.; David, D.; Moreaud, O.

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive) episodic models of memory [4].

  3. Associative visual agnosia: a case study.

    Science.gov (United States)

    Charnallet, A; Carbonnel, S; David, D; Moreaud, O

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

  4. Study of obesity associated proopiomelanocortin gene polymorphism

    African Journals Online (AJOL)

    Farida El-Baz Mohamed

    2016-03-10

    Mar 10, 2016 ... Study of obesity associated proopiomelanocortin ... Binge Eating Disorder (BED) by The Diagnostic and Statistical Manual of Mental Disorders, Fifth ... Cases were compared to fifty age-, sex- and pubertal stage-matched healthy non obese children and adolescents as a control group. The work was carried ...

  5. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of

  6. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    Jane

    2011-09-28

    Sep 28, 2011 ... We wanted to determine the association between alcohol addiction and ethanol metabolizing genes and neurotransmitter related genes. MATERIALS AND METHODS. Study population. A total of 332 DNA samples from unrelated Chinese Han population in Yunnan region were obtained (214 controls and ...

  7. Chapter 11: Genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    William S Bush

    Full Text Available Genome-wide association studies (GWAS have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.

  8. Genome-Wide Association Studies of Cancer

    Science.gov (United States)

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

  9. Associative Visual Agnosia: A Case Study

    Directory of Open Access Journals (Sweden)

    A. Charnallet

    2008-01-01

    Full Text Available We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive episodic models of memory [4].

  10. Microorganisms associated particulate matter: a preliminary study.

    Science.gov (United States)

    Alghamdi, Mansour A; Shamy, Magdy; Redal, Maria Ana; Khoder, Mamdouh; Awad, Abdel Hameed; Elserougy, Safaa

    2014-05-01

    This study aims to determine the microbiological quality of particulate matter (PM) in an urban area in Jeddah, Saudi Arabia, during December 2012 to April 2013. This was achieved by the determination of airborne bacteria, fungi, and actinobacteria associated PM10 and PM2.5, as well as their relationships with gaseous pollutants, O3, SO2 and NO2, and meteorological factors (T°C, RH% and Ws). High volume samplers with PM10 and PM2.5 selective sizes, and glass fiber filters were used to collect PM10 and PM2.5, respectively. The filters were suspended in buffer phosphate and aliquots were spread plated onto the surfaces of trypticase soy agar, malt extract agar, and starch casein agar media for counting of bacteria, fungi and actinobacteria-associated PM, respectively. PM10 and PM2.5 concentrations averaged 159.9 μg/m(3) and 60 μg/m(3), respectively, with the ratio of PM2.5/PM10 averaged ~0.4. The concentrations of O3, SO2 and NO2 averaged 35.73 μg/m(3), 38.1μg/m(3) and 52.5 μg/m(3), respectively. Fungi and actinobacteria associated PM were found in lower concentrations than bacteria. The sum of microbial loads was higher in PM10 than PM2.5, however a significant correlation (r=0.57, P ≤ 0.05) was found between the sum of microbial loads associated PM10 and PM2.5. Aspergillus fumigatus and Aspergillus niger were the common fungal types associated PM. Temperature significantly correlated with both PM10 (r=0.44), and PM2.5 (r=0.5). Significant negative correlations were found between O3 and PM2.5 (r=-0.47), and between SO2 with PM10 (r=-0.48). Wind speed positively correlated with airborne microorganisms associated PM. The regression model showed that the inverse PM2.5 concentration (1/PM2.5) was a significant determinant of fungal count associated PM. Chemical processes and environmental factors could affect properties of PM and in turn its biological quality. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Proteomic studies associated with Parkinson's disease.

    Science.gov (United States)

    Kasap, Murat; Akpinar, Gurler; Kanli, Aylin

    2017-03-01

    Parkinson's disease (PD) is an insidious disorder affecting more than 1-2% of the population over the age of 65. Understanding the etiology of PD may create opportunities for developing new treatments. Genomic and transcriptomic studies are useful, but do not provide evidence for the actual status of the disease. Conversely, proteomic studies deal with proteins, which are real time players, and can hence provide information on the dynamic nature of the affected cells. The number of publications relating to the proteomics of PD is vast. Therefore, there is a need to evaluate the current proteomics literature and establish the connections between the past and the present to foresee the future. Areas covered: PubMed and Web of Science were used to retrieve the literature associated with PD proteomics. Studies using human samples, model organisms and cell lines were selected and reviewed to highlight their contributions to PD. Expert commentary: The proteomic studies associated with PD achieved only limited success in facilitating disease diagnosis, monitoring and progression. A global system biology approach using new models is needed. Future research should integrate the findings of proteomics with other omics data to facilitate both early diagnosis and the treatment of PD.

  12. Gastroschisis and associated defects: an international study.

    LENUS (Irish Health Repository)

    Mastroiacovo, Pierpaolo

    2007-04-01

    Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolated cases and a thorough case-by-case review.

  13. coMET: visualisation of regional epigenome-wide association scan results and DNA co-methylation patterns.

    Science.gov (United States)

    Martin, Tiphaine C; Yet, Idil; Tsai, Pei-Chien; Bell, Jordana T

    2015-04-28

    Epigenome-wide association scans (EWAS) are an increasingly powerful and widely-used approach to assess the role of epigenetic variation in human complex traits. However, this rapidly emerging field lacks dedicated visualisation tools that can display features specific to epigenetic datasets. We developed coMET, an R package and online tool for visualisation of EWAS results in a genomic region of interest. coMET generates a regional plot of epigenetic-phenotype association results and the estimated DNA methylation correlation between CpG sites (co-methylation), with further options to visualise genomic annotations based on ENCODE data, gene tracks, reference CpG-sites, and user-defined features. The tool can be used to display phenotype association signals and correlation patterns of microarray or sequencing-based DNA methylation data, such as Illumina Infinium 450k, WGBS, or MeDIP-seq, as well as other types of genomic data, such as gene expression profiles. The software is available as a user-friendly online tool from http://epigen.kcl.ac.uk/comet and as an R Bioconductor package. Source code, examples, and full documentation are also available from GitHub. Our new software allows visualisation of EWAS results with functional genomic annotations and with estimation of co-methylation patterns. coMET is available to a wide audience as an online tool and R package, and can be a valuable resource to interpret results in the fast growing field of epigenetics. The software is designed for epigenetic data, but can also be applied to genomic and functional genomic datasets in any species.

  14. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  15. Hierarchical Naive Bayes for genetic association studies.

    Science.gov (United States)

    Malovini, Alberto; Barbarini, Nicola; Bellazzi, Riccardo; de Michelis, Francesca

    2012-01-01

    Genome Wide Association Studies represent powerful approaches that aim at disentangling the genetic and molecular mechanisms underlying complex traits. The usual "one-SNP-at-the-time" testing strategy cannot capture the multi-factorial nature of this kind of disorders. We propose a Hierarchical Naïve Bayes classification model for taking into account associations in SNPs data characterized by Linkage Disequilibrium. Validation shows that our model reaches classification performances superior to those obtained by the standard Naïve Bayes classifier for simulated and real datasets. In the Hierarchical Naïve Bayes implemented, the SNPs mapping to the same region of Linkage Disequilibrium are considered as "details" or "replicates" of the locus, each contributing to the overall effect of the region on the phenotype. A latent variable for each block, which models the "population" of correlated SNPs, can be then used to summarize the available information. The classification is thus performed relying on the latent variables conditional probability distributions and on the SNPs data available. The developed methodology has been tested on simulated datasets, each composed by 300 cases, 300 controls and a variable number of SNPs. Our approach has been also applied to two real datasets on the genetic bases of Type 1 Diabetes and Type 2 Diabetes generated by the Wellcome Trust Case Control Consortium. The approach proposed in this paper, called Hierarchical Naïve Bayes, allows dealing with classification of examples for which genetic information of structurally correlated SNPs are available. It improves the Naïve Bayes performances by properly handling the within-loci variability.

  16. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  17. Disentangling pooled triad genotypes for association studies.

    Science.gov (United States)

    Shi, Min; Umbach, David M; Weinberg, Clarice R

    2014-09-01

    Association studies that genotype affected offspring and their parents (triads) offer robustness to genetic population structure while enabling assessments of maternal effects, parent-of-origin effects, and gene-by-environment interaction. We propose case-parents designs that use pooled DNA specimens to make economical use of limited available specimens. One can markedly reduce the number of genotyping assays required by randomly partitioning the case-parent triads into pooling sets of h triads each and creating three pools from every pooling set, one pool each for mothers, fathers, and offspring. Maximum-likelihood estimation of relative risk parameters proceeds via log-linear modeling using the expectation-maximization algorithm. The approach can assess offspring and maternal genetic effects and accommodate genotyping errors and missing genotypes. We compare the power of our proposed analysis for testing offspring and maternal genetic effects to that based on a difference approach and that of the gold standard based on individual genotypes, under a range of allele frequencies, missing parent proportions, and genotyping error rates. Power calculations show that the pooling strategies cause only modest reductions in power if genotyping errors are low, while reducing genotyping costs and conserving limited specimens. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  18. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

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

  19. Archaeological and Paleontological Investigation at Kalaeloa (Barber’s Point), Honouliuli, ’EWA, O’Ahu Island, Federal Study Areas 1a and 1b, and State of Hawaii Optional Area 1,

    Science.gov (United States)

    1981-07-01

    kukui nut shell, charcoal, waterworn Ilasalt. and coral. Among the gastropods, pipipi ( Nerita picea) iz ftlh - 74- 7’AD Af28 230 ARCHAEOLOGICAL AND...present to a lesser degree than the Nerita picea. The pelecypods were represented by Tellina, Brachidontes, Periglypta, Pinctada and Isognomon. Among...rose considerably and consisted of large quantities of pipipi ( Nerita - picea) and Brachidontes (90% of the midden) with some Conus, Cypraea, -89- I

  20. The Danish Association for Science and Technology Studies

    DEFF Research Database (Denmark)

    A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments.......A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments....

  1. Genome-wide association study of sporadic brain arteriovenous malformations

    NARCIS (Netherlands)

    Weinsheimer, S.; Bendjilali, N.; Nelson, J.; Guo, D.E.; Zaroff, J.G.; Sidney, S.; McCulloch, C.E.; Salman, R. Al-Shahi; Berg, J.N.; Koeleman, B.P.C.; Simon, M.; Bostroem, A.; Fontanella, M.; Sturiale, C.L.; Pola, R.; Puca, A.; Lawton, M.T.; Young, W.L.; Pawlikowska, L.; Klijn, C.J.M.; Kim, H.

    2016-01-01

    BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide

  2. Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia

    DEFF Research Database (Denmark)

    Carrera, Noa; Arrojo, Manuel; Sanjuán, Julio

    2012-01-01

    Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, ...

  3. An association study between polymorphism of alcohol ...

    African Journals Online (AJOL)

    The aim of this study was to identify the genetic risk factors which include alcohol metabolizing genes and neurotransmitter related genes for alcoholism in Yunnan Han population. Eight allelic variants of five genes were genotyped from 332 Yunnan Han individuals (including 118 alcohol-dependent patients (DSM-IV ...

  4. A study of diabetes associated oral manifestations

    Directory of Open Access Journals (Sweden)

    T Shanmugam Kathiresan

    2017-01-01

    Full Text Available Aim: The aim of this work was to determine the frequency of oral changes in diabetic patients and to study the relationship between periodontal disease and diabetes mellitus. Materials and Methods: The study sample consisted of 440 known diabetic patients between the age group of 20–80 years, of which 212 were males and 228 were females. One hundred and six patients were below 40 years, 138 patients between 41 and 50 years, 97 in 51–60 years, and 99 above 60 years of age. Data were statistically analyzed by Student's t-test. Results: Nearly 57% of the patients showed a Russell's Periodontal Index score of 2–4.9, which suggested an established periodontal disease. Risk factors for the people above the age of 40 years to develop diabetes were 76%. Conclusion: The frequency of oral manifestations in diabetic patients was significantly high, hence showing a relationship of gingival and periodontal diseases with diabetes mellitus.

  5. CCNA Cisco Certified Network Associate Study Guide

    CERN Document Server

    Lammle, Todd

    2011-01-01

    Learn from the Best - Cisco Networking Authority Todd LammleWritten by Cisco networking authority Todd Lammle, this comprehensive guide has been completely updated to reflect the latest CCNA 640-802 exam. Todd's straightforward style provides lively examples, hands on and written labs, easy-to-understand analogies, and real-world scenarios that will not only help you prepare for the exam, but also give you a solid foundation as a Cisco networking professional.This Study Guide teaches you how toDescribe how a network worksConfigure, verify and troubleshoot a switch with VLANs and interswitch co

  6. Genome-wide association study of multiplex schizophrenia pedigrees

    DEFF Research Database (Denmark)

    Levinson, Douglas F; Shi, Jianxin; Wang, Kai

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  7. Association studies of lung function in mice.

    Science.gov (United States)

    Ganguly, K; Schulz, H

    2008-07-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and an accelerating decline of lung function is the earliest and a major indicator of the onset of COPD. Therefore it has become necessary to understand the genetic basis of this complex physiological trait in order to determine the potential susceptibility factors of this disease. REINHARD et al (2005) performed the genome wide linkage analysis study with inbred mice having extremely divergent lung function (C3H/HeJ versus JF1/Msf) and identified multiple Quantitative Trait Loci (QTLs) on mouse chromosomes (mCh) 5, 15, 17, and 19 with Logarithm of odd (LOD) scores > or = 4. Significant linkages to total lung capacity (TLC) were detected on mCh 15 and 17, to dead space volume (VD) and lung compliance (C(L)) on mCh 5 and 15, to C(L) on mCh 19, and to diffusing capacity for CO (D(co)) on mCh 15 and 17. Several of the mouse chromosomal regions identified were syntenic to human chromosomal regions identified with linkage to FEV1 (forced expiratory volume-1 second), FVC (forced vital capacity), or FEV1/FVC in separate studies. Using a systematic approach of expression QTL (e-QTL) strategy and exon-wise sequencing of suggested candidate genes followed by predicted protein structure and property, GANGULY et al (2007) recently proposed four candidate genes for lung function in mice. They are superoxide dismutase 3, extracellular [SOD3; mCh 5: V(D)], trefoil factor 2 (TFF2; mCh 17: TLC and D(co)), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2; mCh 15:TLC and C(L)), and relaxin 1 (RLN1; mCh 19; CL and CL/TLC). As a part of functional validation, gene-targeted Sod3-/- mice were detected with increased conducting airway volume (V(D)/TLC) compared with strain-matched control Sod3+/+ mice, consistent with the QTL on mCh 5. Findings with gene-targeted mice suggested that SOD3 is a contributing factor defining the complex trait of conducting airway volume. The human variation in

  8. 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; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Hassanali, Neelam; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; Meduri, Eshwar; di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O'Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sandling, Johanna; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Soranzo, Nicole; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun-Po; Zondervan, Krina T.

    2015-01-01

    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. PMID:26021296

  9. A descriptive study of biological and psychosocial factors associated ...

    African Journals Online (AJOL)

    Conclusion: This study supports previous findings that a significant association exists between maternal and childhood obesity. The association between BMI and psychotropic medication, nutritional intake and eating habits, and level of physical activity could not be confirmed in our study. The study results were limited by ...

  10. Sample size computation for association studies using case–parents ...

    Indian Academy of Sciences (India)

    sample size for case–control association studies is discussed. Materials and methods. Parameter settings. We consider a candidate locus with two alleles A and a where. A is putatively associated with the disease status (increasing. Keywords. sample size; association tests; genotype relative risk; power; autism. Journal of ...

  11. The Canadian Association for the Study of International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Canadian Association for the Study of International Development (CASID) was founded in 1989 to provide a forum for Canadian scholars, policymakers, and civil society to meet and exchange views. It is the only Canadian learned society devoted to the study of international development. The Association's journal, the ...

  12. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha

    2013-01-01

    Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this ...

  13. What is the probability of replicating a statistically significant association in genome-wide association studies?

    Science.gov (United States)

    Jiang, Wei; Xue, Jing-Hao; Yu, Weichuan

    2017-11-01

    The goal of genome-wide association studies (GWASs) is to discover genetic variants associated with diseases/traits. Replication is a common validation method in GWASs. We regard an association as true finding when it shows significance in both primary and replication studies. A question worth pondering is what is the probability of a primary association (i.e. a statistically significant association in the primary study) being validated in the replication study? This article systematically reviews the answers to this question from different points of view. As Bayesian methods can help us integrate out the uncertainty about the underlying effect of the primary association, we will mainly focus on the Bayesian view in this article. We refer the Bayesian replication probability as the replication rate (RR). We further describe an estimation method for RR, which makes use of the summary statistics from the primary study. We can use the estimated RR to determine the sample size of the replication study and to check the consistency between the results of the primary study and those of the replication study. We describe an R-package to estimate and apply RR in GWASs. Simulation and real data experiments show that the estimated RR has good prediction and calibration performance. We also use these data to demonstrate the usefulness of RR. The R-package is available at http://bioinformatics.ust.hk/RRate.html. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Novel Loci Associated with Usual Sleep Duration: The CHARGE Consortium Genome-Wide Association Study

    Science.gov (United States)

    Gottlieb, Daniel J.; Hek, Karin; Chen, Ting-hsu; Watson, Nathaniel F.; Eiriksdottir, Gudny; Byrne, Enda M.; Cornelis, Marilyn; Warby, Simon C.; Bandinelli, Stefania; Cherkas, Lynn; Evans, Daniel S.; Grabe, Hans J.; Lahti, Jari; Li, Man; Lehtimäki, Terho; Lumley, Thomas; Marciante, Kristin D.; Pérusse, Louis; Psaty, Bruce M.; Robbins, John; Tranah, Gregory J.; Vink, Jacqueline M.; Wilk, Jemma B.; Stafford, Jeanette M.; Bellis, Claire; Biffar, Reiner; Bouchard, Claude; Cade, Brian; Curhan, Gary C.; Eriksson, Johan G.; Ewert, Ralf; Ferrucci, Luigi; Fülöp, Tibor; Gehrman, Philip R.; Goodloe, Robert; Harris, Tamara B.; Heath, Andrew C.; Hernandez, Dena; Hofman, Albert; Hottenga, Jouke-Jan; Hunter, David J.; Jensen, Majken K.; Johnson, Andrew D.; Kähönen, Mika; Kao, Linda; Kraft, Peter; Larkin, Emma K.; Lauderdale, Diane S.; Luik, Annemarie I.; Medici, Marco; Montgomery, Grant W.; Palotie, Aarno; Patel, Sanjay R.; Pistis, Giorgio; Porcu, Eleonora; Quaye, Lydia; Raitakari, Olli; Redline, Susan; Rimm, Eric B.; Rotter, Jerome I.; Smith, Albert V.; Spector, Tim D.; Teumer, Alexander; Uitterlinden, André G.; Vohl, Marie-Claude; Widen, Elisabeth; Willemsen, Gonneke; Young, Terry; Zhang, Xiaoling; Liu, Yongmei; Blangero, John; Boomsma, Dorret I.; Gudnason, Vilmundur; Hu, Frank; Mangino, Massimo; Martin, Nicholas G.; O’Connor, George T.; Stone, Katie L.; Tanaka, Toshiko; Viikari, Jorma; Gharib, Sina A.; Punjabi, Naresh M.; Räikkönen, Katri; Völzke, Henry; Mignot, Emmanuel; Tiemeier, Henning

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study of usual sleep duration was conducted using 18 population-based cohorts totaling 47,180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35–80 kb upstream from the thyroid-specific transcription factor PAX8 (lowest p=1.1 ×10−9). This finding was replicated in an African-American sample of 4771 individuals (lowest p=9.3 × 10−4). The strongest combined association was at rs1823125 (p=1.5 × 10−10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 minutes longer per night. The alleles associated with longer sleep duration were associated in previous genome-wide association studies with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease. PMID:25469926

  15. A systematic analysis of the association studies between CASP8 ...

    Indian Academy of Sciences (India)

    However, in Australia, Finland, Spain, Sweden and U.S., there is no significant association between CASP8 D302H and breast cancer risk (Figure 3). No heterogeneity was found between groups or between studies. Hence, the association between CASP8 D302H and breast cancer risk may be country variable. Previously ...

  16. A Discovery Genome-Wide Association Study of Entrepreneurship

    Science.gov (United States)

    Quaye, Lydia; Nicolaou, Nicos; Shane, Scott; Mangino, Massimo

    2012-01-01

    To identify specific genetic variants influencing the phenotype of entrepreneurship, we conducted a genome-wide association study (GWAS) with 3,933 Caucasian females from the TwinsUK Adult Twin Registry. Following stringent genotype quality control, GWAF (genome-wide association analyses for family data) software was used to assess the association…

  17. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects

    National Research Council Canada - National Science Library

    Ramachandran, Dhanya; Zeng, Zhen; Locke, Adam E; Mulle, Jennifer G; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford L; Capone, George T; Reeves, Roger H; Maslen, Cheryl L; Cutler, David J; Feingold, Eleanor; Sherman, Stephanie L; Zwick, Michael E

    2015-01-01

    .... We performed a genome-wide association study using logistic regression analysis on 452 individuals with Down syndrome, consisting of 210 cases with complete atrioventricular septal defects and 242...

  18. Robust ranks of true associations in genome-wide case-control association studies.

    Science.gov (United States)

    Zheng, Gang; Joo, Jungnam; Lin, Jing-Ping; Stylianou, Mario; Waclawiw, Myron A; Geller, Nancy L

    2007-01-01

    In whole-genome association studies, at the first stage, all markers are tested for association and their test statistics or p-values are ranked. At the second stage, some most significant markers are further analyzed by more powerful statistical methods. This helps reduce the number of hypotheses to be corrected for in multiple testing. Ranks of true associations in genome-wide scans using a single test statistic have been studied. In a case-control design for association, the trend test has been proposed. However, three different trend tests, optimal for the recessive, additive, and dominant models, respectively, are available for each marker. Because the true genetic model is unknown, we rank markers based on multiple test statistics or test statistics robust to model mis-specification. We studied this problem with application to Problem 3 of Genetic Analysis Workshop 15. An independent simulation study was also conducted to further evaluate the proposed procedure.

  19. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

    Directory of Open Access Journals (Sweden)

    Jiali Han

    2008-05-01

    Full Text Available We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62 and p = 7.46x10(-127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14, eye color (p = 6.1x10(-13, and skin tanning response to sunlight (p = 3.9x10(-89. A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52. One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

  20. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation.

    Science.gov (United States)

    Han, Jiali; Kraft, Peter; Nan, Hongmei; Guo, Qun; Chen, Constance; Qureshi, Abrar; Hankinson, Susan E; Hu, Frank B; Duffy, David L; Zhao, Zhen Zhen; Martin, Nicholas G; Montgomery, Grant W; Hayward, Nicholas K; Thomas, Gilles; Hoover, Robert N; Chanock, Stephen; Hunter, David J

    2008-05-16

    We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0x10(-62) and p = 7.46x10(-127), respectively. The IRF4 SNP was also associated with skin color (p = 6.2x10(-14)), eye color (p = 6.1x10(-13)), and skin tanning response to sunlight (p = 3.9x10(-89)). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation.

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

    OpenAIRE

    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.

    2015-01-01

    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 meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies...

  2. Progress of genome-wide association studies of ankylosing spondylitis

    Science.gov (United States)

    Li, Zhixiu; Brown, Matthew A

    2017-01-01

    Ankylosing spondylitis (AS) is an immune-mediated arthritis which primarily affects the spine and sacroiliac joints. Significant progress has been made in discovery of genetic associations with AS by genome-wide association studies (GWAS) over past decade. These findings have uncovered novel pathways involved pathogenesis of the disease and have led to introduction of novel therapeutic treatments for AS. In this Review, we discuss the genetic variations associated with AS identified by GWAS, the major pathways revealed by these AS-associated variations and critical cell types involved in AS development. PMID:29333268

  3. Genome-wide association study of electrocardiographic parameters identifies a new association for PR interval and confirms previously reported associations.

    Science.gov (United States)

    Sano, Motoaki; Kamitsuji, Shigeo; Kamatani, Naoyuki; Hong, Kyung-Won; Han, Bok-Ghee; Kim, Yeonjung; Kim, Jong Wook; Aizawa, Yoshiyasu; Fukuda, Keiichi

    2014-12-15

    Previous reports have described several associations of PR, QRS, QT and heart rate with genomic variations by genome-wide association studies (GWASs). In the present study, we examined the association of ∼2.5 million SNPs from 2994 Japanese healthy volunteers obtained from the JPDSC database with electrocardiographic parameters. We confirmed associations of PR interval, QRS duration and QT interval in individuals of Japanese ancestry with 11 of the 45 SNPs (6 of 20 for QT, 5 of 19 for PR and 0 of 6 for QRS) observed among individuals of European, African and Asian (Indian and Korean) ancestries. Those results indicate that many of the electrocardiographic associations with genes are shared by different ethnic groups including Japanese. Possible novel associations found in this study were validated by Korean data. As a result, we identified a novel association of SNP rs4952632[G] (maps near SLC8A1, sodium-calcium exchanger) (P = 7.595 × 10(-6)) with PR interval in Japanese individuals, and replication testing among Koreans confirmed the association of the same SNP with prolonged PR interval. Meta-analysis of the Japanese and Korean datasets demonstrated highly significant associations of SNP rs4952632[G] with a 2.325-ms (95% CI, 1.693-2.957 ms) longer PR interval per minor allele copy (P = 5.598 × 10(-13)). Cell-type-specific SLC8A1 knockout mice have demonstrated a regulatory role of sodium-calcium exchanger in automaticity and conduction in sinoatrial node, atrium and atrioventricular node. Our findings support a functional role of sodium-calcium exchanger in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Genome-Wide Association Studies of Multiple Keratinocyte Cancers

    Science.gov (United States)

    Verkouteren, Joris A. C.; Hofman, Albert; Uitterlinden, André G.; Kraft, Peter; Turman, Constance; Han, Jiali; Cho, Eunyoung; Murabito, Joanne M.; Levy, Daniel; Qureshi, Abrar A.; Nijsten, Tamar

    2017-01-01

    There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10-4). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene. PMID:28081215

  5. Genome-Wide Association Studies of Multiple Keratinocyte Cancers.

    Directory of Open Access Journals (Sweden)

    Luba M Pardo

    Full Text Available There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs, but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs are associated with susceptibility for mKCs. A genome-wide association study (GWAS of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1. We sought to replicate the most significant statistical associations (p-value≤ 5.5x10-6 in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ≤5.5x10-6 were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7. In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis, and found that rs1805007 (MC1R locus was significantly associated with risk of mKCs (p-value = 2.80x10-4. Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007 located at the MC1R gene.

  6. Association between erectile dysfunction and chronic periodontitis: A clinical study

    Directory of Open Access Journals (Sweden)

    Ranjit Singh Uppal

    2014-01-01

    Conclusion: It may be concluded that chronic periodontitis and ED are associated with each other. However, further large scale studies with confounder analysis and longitudinal follow-up are warranted to explore the link between these two diseases.

  7. Rh factor is associated with individual radiosensitivity: A cytogenetic study

    OpenAIRE

    Khosravifarsani, Meysam; Monfared, Ali Shabestani; Borzoueisileh, Sajad

    2016-01-01

    Introduction Radiosensitivity is an inherent trait, associated with a raised reaction to ionizing radiation on the human body. In radiotherapy and radiation protection fields, individualization of the patient?s treatment is one of the main topics. With the goal of determining biomarkers capable of anticipating normal tissue side reactions, we studied the association between the Rh factor and radiosensitivity. Methods This experimental study was carried out from January to June 2014 among 50 n...

  8. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia.......Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  9. Genome-wide association study of sporadic brain arteriovenous malformations

    OpenAIRE

    Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G.; Sidney, Stephen; McCulloch, Charles E.; Al-Shahi Salman, Rustam; Berg, Jonathan N; Bobby P. C. Koeleman; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto

    2016-01-01

    BACKGROUND: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium.METHODS: The Caucasian discovery cohort included 515 BAVM c...

  10. Leveraging the HapMap Correlation Structure in Association Studies

    OpenAIRE

    Zaitlen, Noah; Kang, Hyun Min; Eskin, Eleazar; Halperin, Eran

    2007-01-01

    Recent high-throughput genotyping technologies, such as the Affymetrix 500k array and the Illumina HumanHap 550 beadchip, have driven down the costs of association studies and have enabled the measurement of single-nucleotide polymorphism (SNP) allele frequency differences between case and control populations on a genomewide scale. A key aspect in the efficiency of association studies is the notion of “indirect association,” where only a subset of SNPs are collected to serve as proxies for th...

  11. The relative contribution of DNA methylation and genetic variants on protein biomarkers for human diseases.

    Directory of Open Access Journals (Sweden)

    Muhammad Ahsan

    2017-09-01

    Full Text Available Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs. We performed epigenome-wide association study (EWAS and genome-wide association study (GWAS analyses, and integrated biomarker, DNA methylation and SNP data using between 698 and 1033 samples depending on data availability for the different analyses. We identified 124 and 45 loci (Bonferroni adjusted P < 0.05 with effect sizes up to 0.22 standard units' change per 1% change in DNA methylation levels and up to four standard units' change per copy of the effective allele in the EWAS and GWAS respectively. Most GWAS loci were cis-regulatory whereas most EWAS loci were located in trans. Eleven EWAS loci were associated with multiple biomarkers, including one in NLRC5 associated with CXCL11, CXCL9, IL-12, and IL-18 levels. All EWAS signals that overlapped with a GWAS locus were driven by underlying genetic variants and three EWAS signals were confounded by smoking. While some cis-regulatory SNPs for biomarkers appeared to have an effect also on DNA methylation levels, cis-regulatory SNPs for DNA methylation were not observed to affect biomarker levels. We present associations between protein biomarker and DNA methylation levels at numerous loci in the genome. The associations are likely to reflect the underlying pattern of genetic variants, specific environmental exposures, or represent secondary effects to the pathogenesis of disease.

  12. Epigenome-wide association studies identify DNA methylation associated with kidney function.

    Science.gov (United States)

    Chu, Audrey Y; Tin, Adrienne; Schlosser, Pascal; Ko, Yi-An; Qiu, Chengxiang; Yao, Chen; Joehanes, Roby; Grams, Morgan E; Liang, Liming; Gluck, Caroline A; Liu, Chunyu; Coresh, Josef; Hwang, Shih-Jen; Levy, Daniel; Boerwinkle, Eric; Pankow, James S; Yang, Qiong; Fornage, Myriam; Fox, Caroline S; Susztak, Katalin; Köttgen, Anna

    2017-11-03

    Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation.

  13. A genome wide association study identifies common variants associated with lipid levels in the Chinese population.

    Directory of Open Access Journals (Sweden)

    Li Zhou

    Full Text Available Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC, triglycerides (TG, low-density lipoprotein cholesterol (LDL and high-density lipoprotein cholesterol (HDL in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16, 1.38 × 10(-6 and 5.59 × 10(-9, respectively. These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

  14. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

    Science.gov (United States)

    Gottlieb, D J; Hek, K; Chen, T-H; Watson, N F; Eiriksdottir, G; Byrne, E M; Cornelis, M; Warby, S C; Bandinelli, S; Cherkas, L; Evans, D S; Grabe, H J; Lahti, J; Li, M; Lehtimäki, T; Lumley, T; Marciante, K D; Pérusse, L; Psaty, B M; Robbins, J; Tranah, G J; Vink, J M; Wilk, J B; Stafford, J M; Bellis, C; Biffar, R; Bouchard, C; Cade, B; Curhan, G C; Eriksson, J G; Ewert, R; Ferrucci, L; Fülöp, T; Gehrman, P R; Goodloe, R; Harris, T B; Heath, A C; Hernandez, D; Hofman, A; Hottenga, J-J; Hunter, D J; Jensen, M K; Johnson, A D; Kähönen, M; Kao, L; Kraft, P; Larkin, E K; Lauderdale, D S; Luik, A I; Medici, M; Montgomery, G W; Palotie, A; Patel, S R; Pistis, G; Porcu, E; Quaye, L; Raitakari, O; Redline, S; Rimm, E B; Rotter, J I; Smith, A V; Spector, T D; Teumer, A; Uitterlinden, A G; Vohl, M-C; Widen, E; Willemsen, G; Young, T; Zhang, X; Liu, Y; Blangero, J; Boomsma, D I; Gudnason, V; Hu, F; Mangino, M; Martin, N G; O'Connor, G T; Stone, K L; Tanaka, T; Viikari, J; Gharib, S A; Punjabi, N M; Räikkönen, K; Völzke, H; Mignot, E; Tiemeier, H

    2015-10-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

  15. Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease

    Science.gov (United States)

    Wang, Kai; Zhang, Haitao; Kugathasan, Subra; Annese, Vito; Bradfield, Jonathan P.; Russell, Richard K.; Sleiman, Patrick M.A.; Imielinski, Marcin; Glessner, Joseph; Hou, Cuiping; Wilson, David C.; Walters, Thomas; Kim, Cecilia; Frackelton, Edward C.; Lionetti, Paolo; Barabino, Arrigo; Van Limbergen, Johan; Guthery, Stephen; Denson, Lee; Piccoli, David; Li, Mingyao; Dubinsky, Marla; Silverberg, Mark; Griffiths, Anne; Grant, Struan F.A.; Satsangi, Jack; Baldassano, Robert; Hakonarson, Hakon

    2009-01-01

    Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 × 10−5). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies. PMID:19249008

  16. Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.

    Science.gov (United States)

    Ransohoff, Katherine J; Wu, Wenting; Cho, Hyunje G; Chahal, Harvind C; Lin, Yuan; Dai, Hong-Ji; Amos, Christopher I; Lee, Jeffrey E; Tang, Jean Y; Hinds, David A; Han, Jiali; Wei, Qingyi; Sarin, Kavita Y

    2017-03-14

    Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M.D. Anderson Cancer Center. We performed a combined meta-analysis totaling 6,628 melanoma cases and 287,591 controls. Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance. In addition, we uncover a novel polymorphism, rs187843643 (OR = 1.96; 95% CI = [1.54, 2.48]; P = 3.53 x 10-8), associated with melanoma. The SNP rs187842643 lies within a noncoding RNA 177kb downstream of BASP1 (brain associated protein-1). We find that BASP1 expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis.

  17. Power analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Klein Robert J

    2007-08-01

    Full Text Available Abstract Background Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. Results The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. Conclusion Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.

  18. Prediction of disease and phenotype associations from genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Stephanie N Lewis

    Full Text Available BACKGROUND: Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  19. Population structure and association mapping studies for important ...

    Indian Academy of Sciences (India)

    Large phenotypic variability was observed for the agronomic traits under study indicating suitability of the genotypes for association studies. The maximum values for plant height, pods per plant, seeds per pod, 100-seed weight and seed yield per plant were approximately two and half to three times more than the minimum ...

  20. A genome-wide association study of aging

    NARCIS (Netherlands)

    S. Walter (Stefan); G. Atzmon (Gil); E.W. Demerath (Ellen); M. Garcia (Melissa); R.C. Kaplan (Robert); M. Kumari (Meena); K.L. Lunetta (Kathryn); Y. Milaneschi (Yuri); T. Tanaka (Toshiko); G.J. Tranah (Gregory); U. Völker (Uwe); L. Yu (Lei); A.M. Arnold (Alice); E.J. Benjamin (Emelia); R. Biffar (Reiner); A.S. Buchman (Aron); E.A. Boerwinkle (Eric); D. Couper (David); P.L. de Jager (Philip); D.A. Evans (Denis); T.B. Harris (Tamara); W. Hoffmann (Wolfgang); A. Hofman (Albert); D. Karasik (David); D.P. Kiel (Douglas); T. Kocher (Thomas); M. Kuningas (Maris); L.J. Launer (Lenore); K. Lohman (Kurt); P.L. Lutsey (Pamela); J.P. Mackenbach (Johan); K. Marciante (Kristin); B.M. Psaty (Bruce); E.M. Reiman (Eric); J.I. Rotter (Jerome); S. Seshadri (Sudha); M.D. Shardell (Michelle); A.V. Smith (Albert Vernon); P. Tikka-Kleemola (Päivi); J. Walston (Jeremy); M.C. Zillikens (Carola); S. Bandinelli (Stefania); S.E. Baumeister (Sebastian); D.A. Bennett (David); L. Ferrucci (Luigi); V. Gudnason (Vilmundur); M. Kivimaki (Mika); Y. Liu (Yongmei); J. Murabito (Joanne); A.B. Newman (Anne); H.W. Tiemeier (Henning); N. Franceschini (Nora)

    2011-01-01

    textabstractHuman longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2)

  1. Update on bacterial meningitis: epidemiology, trials and genetic association studies

    NARCIS (Netherlands)

    Kasanmoentalib, E. Soemirien; Brouwer, Matthijs C.; van de Beek, Diederik

    2013-01-01

    Bacterial meningitis is a life-threatening disease that continues to inflict a heavy toll. We reviewed recent advances in vaccination, randomized studies on treatment, and genetic association studies in bacterial meningitis. The incidence of bacterial meningitis has decreased after implementation of

  2. A genome-wide association study of anorexia nervosa

    NARCIS (Netherlands)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y|info:eu-repo/dai/nl/369207084; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, Annemarie|info:eu-repo/dai/nl/191430129; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14

  3. Association study of the oestrogen signalling pathway genes in ...

    Indian Academy of Sciences (India)

    Yamamoto T. 2004 Association study using single nucleotide polymorphisms in the estrogen receptor beta (ESR2) gene for preeclampsia. Hypertens Res. 27, 903–909. Murabito J. M., Yang Q., Fox C., Wilson P. W. and Cupples L. A.. 2005a Heritability of age at natural menopause in the Framing- ham Heart Study. J. Clin.

  4. Genetic association studies of obesity in Africa: a systematic review.

    Science.gov (United States)

    Yako, Y Y; Echouffo-Tcheugui, J B; Balti, E V; Matsha, T E; Sobngwi, E; Erasmus, R T; Kengne, A P

    2015-03-01

    Obesity is increasing in Africa, but the underlying genetic background largely remains unknown. We assessed existing evidence on genetic determinants of obesity among populations within Africa. MEDLINE and EMBASE were searched and the bibliographies of retrieved articles were examined. Included studies had to report on the association of a genetic marker with obesity indices and the presence/occurrence of obesity/obesity trait. Data were extracted on study design and characteristics, genetic determinants and effect estimates of associations with obesity indices. According to this data, over 300 polymorphisms in 42 genes have been studied in various population groups within Africa mostly through the candidate gene approach. Polymorphisms in genes such as ACE, ADIPOQ, ADRB2, AGRP, AR, CAPN10, CD36, C7orf31, DRD4, FTO, MC3R, MC4R, SGIP1 and LEP were found to be associated with various measures of obesity. Of the 36 polymorphisms previously validated by genome-wide association studies (GWAS) elsewhere, only FTO and MC4R polymorphisms showed significant associations with obesity in black South Africans, Nigerians and Ghanaians. However, these data are insufficient to establish the true nature of genetic susceptibility to obesity in populations within Africa. There has been recent progress in describing the genetic architecture of obesity among populations within Africa. This effort needs to be sustained via GWAS studies. © 2015 World Obesity.

  5. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  6. Genome-Wide Association Studies of the Human Gut Microbiota

    Science.gov (United States)

    Davenport, Emily R.; Cusanovich, Darren A.; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10−7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  7. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    Science.gov (United States)

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. © 2016 Society for Endocrinology.

  8. Genome-Wide Population-Based Association Study of Extremely Overweight Young Adults - The GOYA Study

    DEFF Research Database (Denmark)

    Paternoster, L.; Evans, D. M.; Nohr, E. A.

    2011-01-01

    Background: Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining,similar to 1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched...

  9. Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

    Science.gov (United States)

    Huang, Minjun; Graham, Britney E; Zhang, Ge; Harder, Reed; Kodaman, Nuri; Moore, Jason H; Muglia, Louis; Williams, Scott M

    2016-01-01

    Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with

  10. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  11. 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.

  12. Power Analysis for Genetic Association Test (PAGEANT) provides insights to challenges for rare variant association studies.

    Science.gov (United States)

    Derkach, Andriy; Zhang, Haoyu; Chatterjee, Nilanjan

    2017-11-28

    Genome-wide association studies are now shifting focus from analysis of common to rare variants. As power for association testing for individual rare variants may often be low, various aggregate level association tests have been proposed to detect genetic loci. Typically, power calculations for such tests require specification of large number of parameters, including effect sizes and allele frequencies of individual variants, making them difficult to use in practice. We propose to approximate power to varying degree of accuracy using a smaller number of key parameters, including the total genetic variance explained by multiple variants within a locus. We perform extensive simulation studies to assess the accuracy of the proposed approximations in realistic settings. Using these simplified power calculations, we develop an analytic framework to obtain bounds on genetic architecture of an underlying trait given results from a genome-wide association studies with rare variants. Finally, we provide insights into the required quality of annotation/functional information for identification of likely causal variants to make meaningful improvement in power. A shiny application that allows a variety of Power Analysis of GEnetic AssociatioN Tests (PAGEANT), in R is made publicly available at https://andrewhaoyu.shinyapps.io/PAGEANT/. nilanjan@jhu.edu. Supplementary data are available at Bioinformatics online.

  13. Psychiatric disorders and obesity: A review of association studies

    Directory of Open Access Journals (Sweden)

    T M Rajan

    2017-01-01

    Full Text Available Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evidence on the association between psychiatric illness and obesity with particular attention to the strength and direction of association and also the possible moderators in each postulated link. Materials and Methods: Systematic electronic searches of MEDLINE through PubMed, ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till October 2016. Generated abstracts were screened for eligibility to be included in the review. Study designs that evaluated the strength of relationship between obesity and psychiatric disorders were included in the study. Quality assessment of included studies was done using the Newcastle–Ottawa checklist tool. Results: From a total of 2424 search results, 21 eligible articles were identified and reviewed. These included studies on obesity and depression (n = 15, obesity and anxiety (four and one each on obesity and personality disorders, eating disorder (ED, attention deficit hyperactivity disorder, and alcohol use. Maximal evidence existed for the association between depression and obesity with longitudinal studies demonstrating a bidirectional link between the two conditions. The odds ratios (ORs were similar for developing depression in obesity (OR: 1.21–5.8 and vice versa (OR: 1.18–3.76 with a stronger association observed in women. For anxiety disorders, evidence was mostly cross-sectional, and associations were of modest magnitude (OR: 1.27–1.40. Among other disorders, obesity, and EDs appear to have a close link (OR: 4.5. Alcohol use appears to be a risk factor for obesity and not vice versa but only among women (OR: 3.84. Conclusion: Obesity and depression have a significant and bidirectional association. Evidence is modest for anxiety disorders and inadequate for other psychiatric

  14. Psychiatric disorders and obesity: A review of association studies

    Science.gov (United States)

    Rajan, TM; Menon, V

    2017-01-01

    Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evidence on the association between psychiatric illness and obesity with particular attention to the strength and direction of association and also the possible moderators in each postulated link. Materials and Methods: Systematic electronic searches of MEDLINE through PubMed, ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till October 2016. Generated abstracts were screened for eligibility to be included in the review. Study designs that evaluated the strength of relationship between obesity and psychiatric disorders were included in the study. Quality assessment of included studies was done using the Newcastle–Ottawa checklist tool. Results: From a total of 2424 search results, 21 eligible articles were identified and reviewed. These included studies on obesity and depression (n = 15), obesity and anxiety (four) and one each on obesity and personality disorders, eating disorder (ED), attention deficit hyperactivity disorder, and alcohol use. Maximal evidence existed for the association between depression and obesity with longitudinal studies demonstrating a bidirectional link between the two conditions. The odds ratios (ORs) were similar for developing depression in obesity (OR: 1.21–5.8) and vice versa (OR: 1.18–3.76) with a stronger association observed in women. For anxiety disorders, evidence was mostly cross-sectional, and associations were of modest magnitude (OR: 1.27–1.40). Among other disorders, obesity, and EDs appear to have a close link (OR: 4.5). Alcohol use appears to be a risk factor for obesity and not vice versa but only among women (OR: 3.84). Conclusion: Obesity and depression have a significant and bidirectional association. Evidence is modest for anxiety disorders and inadequate for other psychiatric conditions

  15. Genetic association studies in osteoarthritis: is it fairytale?

    Science.gov (United States)

    Warner, Sophie C; Valdes, Ana M

    2017-01-01

    Osteoarthritis is a common complex disorder with a strong genetic component. Other identified risk factors such as increasing age and overweight do not fully explain the risk of osteoarthritis. Here, we highlight the main findings from genetic association studies on osteoarthritis to date. Currently, genetic association studies have identified 21 independent susceptibility loci for osteoarthritis. Studies have focused on hip, knee and hand osteoarthritis, as well as posttotal joint replacement and minimum joint space width, a proxy for cartilage thickness. Four distinct loci have recently been identified in a genome-wide association scan on minimum joint space width. The role of mitochondrial DNA variants has been the focus of a recent meta-analysis. Findings have previously been mixed, however, this study suggests a plausible involvement of mitochondrial DNA in the progression of radiographic knee osteoarthritis. Identifying genetic locations of interest provides a framework upon which to base future studies, for example replication analysis and functional work. Genetic association studies have shaped and will continue to shape research in this field. Improving the understanding of osteoarthritis could improve the diagnosis and treatment of the disease and improve quality of life for many individuals.

  16. Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases.

    Science.gov (United States)

    Lee, Wen-Chung

    2016-06-09

    The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use.

  17. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    DEFF Research Database (Denmark)

    Dijkstra, A. E.; Smolonska, J.; van den Berge, M.

    2014-01-01

    of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed...... of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions: Our findings, that SNP rs6577641...

  18. Knee-ligament injuries associated with leg fractures. Prospective study.

    Science.gov (United States)

    Matić, A; Kasić, M; Hudolin, I

    1992-09-01

    It has been proved in 25-35% of the cases that knee-ligament injuries are associated with fracture of the femoral diaphysis. No such association has been confirmed between leg fractures and knee ligaments. In order to find out if this is a coincidence, a prospective study was conducted on 229 patients who had undergone operations for leg fractures at various locations and of variable intensity. It was established in 41 cases (17.34%) that the leg fracture was associated with knee-ligament injuries, resulting in joint instability. A significantly higher percentage of associated ligament lesions was found in open fractures as opposed to closed leg fractures. The examination was carried out with the patient under general or block anesthesia. On the basis of what was established it is recommended that the knee be examined clinically in all leg osteosynthesis cases.

  19. Genome-Wide Association Study of Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Naomi Ogawa

    2010-01-01

    Full Text Available Coronary artery disease (CAD is a multifactorial disease with environmental and genetic determinants. The genetic determinants of CAD have previously been explored by the candidate gene approach. Recently, the data from the International HapMap Project and the development of dense genotyping chips have enabled us to perform genome-wide association studies (GWAS on a large number of subjects without bias towards any particular candidate genes. In 2007, three chip-based GWAS simultaneously revealed the significant association between common variants on chromosome 9p21 and CAD. This association was replicated among other ethnic groups and also in a meta-analysis. Further investigations have detected several other candidate loci associated with CAD. The chip-based GWAS approach has identified novel and unbiased genetic determinants of CAD and these insights provide the important direction to better understand the pathogenesis of CAD and to develop new and improved preventive measures and treatments for CAD.

  20. Association between urbanisation and type 2 diabetes: an ecological study.

    Science.gov (United States)

    Gassasse, Zakariah; Smith, Dianna; Finer, Sarah; Gallo, Valentina

    2017-01-01

    Previous studies have explored the effect of urbanisation on the prevalence of type 2 diabetes (T2D) at regional/national level. The aim of this study is to investigate the association between urbanisation and T2D at country level, worldwide, and to explore the role of intermediate variables (physical inactivity, sugar consumption and obesity). The potential effect modification of gross domestic product (GDP) was also assessed. Data for 207 countries were collected from accessible datasets. Direct acyclic graphs were used to describe the association between urbanisation, T2D and their intermediate variables (physical inactivity, sugar consumption and obesity). Urbanisation was measured as urban percentage (UP) and as agglomeration index (AI). Crude and multivariate linear regression analyses were conducted to explore selected associations. The interaction between urbanisation and T2D across levels of GDP per capita was investigated. The association between urbanisation and T2D diverged by exposure: AI was positively associated, while UP negatively associated with T2D prevalence. Physical inactivity and obesity were statistically significantly associated with increased prevalence of T2D. In middle-income countries (MIC) UP, AI and GDP were significantly associated with T2D prevalence, while in high-income countries (HIC), physical inactivity and obesity were the main determinant of T2D prevalence. The type of urban growth, not urbanisation per se, predicted T2D prevalence at country level. In MIC, population density and GDP were the main determinant of diabetes, while in HIC. these were physical inactivity and obesity. Globalisation is playing an important role in the rise of T2D worldwide.

  1. Gene-Centric Genomewide Association Study via Entropy

    Science.gov (United States)

    Cui, Yuehua; Kang, Guolian; Sun, Kelian; Qian, Minping; Romero, Roberto; Fu, Wenjiang

    2008-01-01

    Genes are the functional units in most organisms. Compared to genetic variants located outside genes, genic variants are more likely to affect disease risk. The development of the human HapMap project provides an unprecedented opportunity for genetic association studies at the genomewide level for elucidating disease etiology. Currently, most association studies at the single-nucleotide polymorphism (SNP) or the haplotype level rely on the linkage information between SNP markers and disease variants, with which association findings are difficult to replicate. Moreover, variants in genes might not be sufficiently covered by currently available methods. In this article, we present a gene-centric approach via entropy statistics for a genomewide association study to identify disease genes. The new entropy-based approach considers genic variants within one gene simultaneously and is developed on the basis of a joint genotype distribution among genetic variants for an association test. A grouping algorithm based on a penalized entropy measure is proposed to reduce the dimension of the test statistic. Type I error rates and power of the entropy test are evaluated through extensive simulation studies. The results indicate that the entropy test has stable power under different disease models with a reasonable sample size. Compared to single SNP-based analysis, the gene-centric approach has greater power, especially when there is more than one disease variant in a gene. As the genomewide genic SNPs become available, our entropy-based gene-centric approach would provide a robust and computationally efficient way for gene-based genomewide association study. PMID:18458106

  2. Genome-wide Association Study of Susceptibility to Particulate Matter-Associated QT Prolongation.

    Science.gov (United States)

    Gondalia, Rahul; Avery, Christy L; Napier, Melanie D; Méndez-Giráldez, Raúl; Stewart, James D; Sitlani, Colleen M; Li, Yun; Wilhelmsen, Kirk C; Duan, Qing; Roach, Jeffrey; North, Kari E; Reiner, Alexander P; Zhang, Zhu-Ming; Tinker, Lesley F; Yanosky, Jeff D; Liao, Duanping; Whitsel, Eric A

    2017-06-08

    Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). Using repeated electrocardiograms (1986–2004), longitudinal data on PMQT-PM10 association (p=2.11×10−8). At PM10 concentrations >90th percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However, QT changed minimally across rs1619661 genotypes at lower PM10 concentrations. The rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from CXCL12, which encodes a chemokine, stromal cell-derived factor 1, that is expressed in cardiomyocytes and decreases calcium influx across the L-type Ca2+ channel. The findings suggest that biologically plausible genetic factors may alter susceptibility to PM10-associated QT prolongation in populations protected by the U.S. Environmental Protection Agency’s National Ambient Air Quality Standards. Independent replication and functional characterization are necessary to validate our findings. https://doi.org/10.1289/EHP347

  3. 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.

  4. Susceptibility to chronic mucus hypersecretion, a genome wide association study.

    Directory of Open Access Journals (Sweden)

    Akkelies E Dijkstra

    Full Text Available Chronic mucus hypersecretion (CMH is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA study of CMH in Caucasian populations.GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years. Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP.A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6, OR = 1.17, located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1 on chromosome 3. The risk allele (G was associated with higher mRNA expression of SATB1 (4.3×10(-9 in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

  5. HIV is associated with airway obstruction: a matched controlled study.

    Science.gov (United States)

    Makinson, Alain; Hayot, Maurice; Eymard-Duvernay, Sabrina; Ribet, Céline; Raffi, François; Pialoux, Gilles; Zucman, David; Poizot-Martin, Isabelle; Bonnet, Fabrice; Abgrall, Sophie; Tattevin, Pierre; Cheret, Antoine; Ferry, Tristan; Mauboussin, Jean-Marc; Marchand, Lucie; Rouzaud, Claire; Reynes, Jacques; Zins, Marie; Le Moing, Vincent

    2018-01-14

    To explore whether airway obstruction is associated with HIV in a cohort of HIV-infected and uninfected smokers. People living with HIV (PLWHIV) participated in the ANRS EP48 HIV CHEST study, an early lung cancer diagnosis study with low-dose chest tomography. HIV-uninfected study participants were from the CONSTANCES cohort. Inclusion criteria were an age greater than 40 years, a smoking history of at least 20 pack-years, and for PLWHIV, a CD4 T-lymphocyte nadir less than 350/μl and last CD4 cell count more than 100 cells/μl. Two randomly selected HIV-uninfected study participants were matched by age and sex with one PLWHIV. Prebronchodilatator forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was the primary outcome, and association of FEV1/FVC ratio less than 0.70 and FEV1 less than 80% of the theoretical value, as a proxy of chronic obstructive pulmonary disease, the secondary outcome. In total, 351 PLWHIV and 702 HIV-uninfected study participants were included. Median age was 50 years, and 17% of study participants were women. Plasma HIV RNA was less than 50 copies/ml in 89% of PLWHIV, with a median CD4 cell count of 573 cells/μl. HIV (β -2.19), age (per 10 years increase; β -2.81), tobacco use (per 5 pack-years increase; β -0.34), and hepatitis C virus serology (β-2.50) were negatively associated with FEV1/FVC. HIV [odds ratio (OR: 1.72)], age (per 10 years increase; OR 1.77), and tobacco use (per 5 pack-years increase; OR 1.11) were significantly associated with the secondary outcome. Our study found a significant association of airway obstruction with HIV status in smokers aged more than 40 years with previous immunodeficiency.

  6. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    Gottlieb, D.J.; Hek, K.; Chen, T.H.; Watson, N.F.; Eiriksdottir, G.; Byrne, E.M.; Cornelis, M.; Warby, S.C.; Bandinelli, S.; Cherkas, L.; Evans, D.S.; Grabe, H.J.; Lahti, J.; Li, M.; Lehtimaki, T.; Lumley, T.; Marciante, K.D.; Pérusse, L.; Psaty, B.M.; Robbins, J.; Tranah, G.J.; Vink, J.M.; Wilk, J.B.; Stafford, J.M.; Bellis, C.; Biffar, R.; Bouchard, C.; Cade, B.; Curhan, G.C.; Eriksson, J.G.; Ewert, R.; Ferrucci, L.; Fulop, T.; Gehrman, P.R.; Goodloe, R.; Harris, T.B.; Heath, A.C.; Hernandez, D.G.; Hofman, A.; Hottenga, J.J.; Hunter, D.J.; Jensen, M.K.; Johnson, A.D.; Kahonen, M.; Kao, L.; Kraft, P.; Larkin, E.K.; Lauderdale, D.S.; Luik, A.I.; Medici, M.; Montgomery, G.W.; Palotie, A.; Patel, S.R.; Pistis, G.; Porcu, E.; Quaye, L.; Raitakari, O.; Redline, S.; Rimm, E.B.; Rotter, J.I.; Smith, A.V.; Spector, T.D.; Teumer, A.; Uitterlinden, A.G.; Vohl, M.C.; Widen, E.; Willemsen, G.; Young, T.; Zhang, X.; Liu, Y.; Blangero, J.; Boomsma, D.I.; Gudnason, V.; Hu, F.; Mangino, M.; Martin, N.G.; O'Connor, G.T.; Stone, K.L.; Tanaka, T.; Viikari, J.; Gharib, S.A.; Punjabi, N.M.; Raikkonen, K.; Völzke, H.; Mignot, E.; Tiemeier, H.

    2015-01-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based

  7. 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, ...

  8. 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

  9. Toppar: An interactive browser for viewing association study results.

    Science.gov (United States)

    Juliusdottir, Thorhildur; Banasik, Karina; Robertson, Neil R; Mott, Richard; McCarthy, Mark I

    2018-01-08

    Data integration and visualization help geneticists make sense of large amounts of data. To help facilitate interpretation of genetic association data we developed Toppar, a customizable visualization tool that stores results from association studies and enables browsing over multiple results, by combining features from existing tools and linking to appropriate external databases. Detailed information on Toppar's features and functionality are on our website http://mccarthy.well.ox.ac.uk/toppar/docs along with instructions on how to download, install and run Toppar. Our online version of Toppar is accessible from the website and can be test-driven using Firefox, Safari or Chrome on sub-sets of publicly available genome-wide association study (GWAS) anthropometric waist and body mass index (BMI) data (Locke, et al., 2015; Shungin, et al., 2015) from the Genetic Investigation of ANthropometric Traits (GIANT) consortium. totajuliusd@gmail.com.

  10. Genome-wide association studies and resting heart rate

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2016-01-01

    Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10 years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms...... and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands...... of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal...

  11. Multi-generational genome wide association studies identify chromosomal regions associated with ascites phenotype.

    Science.gov (United States)

    Tarrant, K J; Dey, S; Kinney, R; Anthony, N B; Rhoads, D D

    2017-06-01

    Ascites is a multi-faceted disease commonly observed in fast growing broilers, which is initiated when the body is insufficiently oxygenated. A series of events follow, including an increase in pulmonary artery pressure, right ventricle hypertrophy, and accumulation of fluid in the abdominal cavity and pericardium. Advances in management practices along with improved selection programs have decreased ascites incidence in modern broilers. However, ascites syndrome remains an economically important disease throughout the world, causing estimated losses of $100 million per year. In this study, a 60 K Illumina SNP BeadChip was used to perform a series of genome wide association studies (GWAS) on the 16th and 18th generation of our relaxed (REL) line descended from a commercial elite broiler line beginning in 1995. Regions significantly associated with ascites incidence were identified on chromosome 2 around 70 megabase pairs (Mbp) and on chromosome Z around 60 Mbp. Five candidate single nucleotide polymorphisms (SNP) were evaluated as indicators for these 2 regions in order to identify association with ascites and right ventricle to total ventricle weight (RVTV) ratios. Chromosome 2 SNP showed an association with RVTV ratios in males phenotyped as ascites resistant and ascites susceptible (P = 0.02 and P = 0.03, respectively). The chromosome Z region also indicates an association with resistant female RVTV values (P = 0.02). Regions of significance identified on chromosomes 2 and Z described in this study will be used as proposed candidate regions for further investigation into the genetics of ascites. This information will lead to a better understanding of the underlying genetics and gene networks contributing to ascites, and thus advances in ascites reduction through commercial breeding schemes. © 2017 Poultry Science Association Inc.

  12. Genome-wide association studies in asthma: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    March ME

    2015-01-01

    Full Text Available Michael E March,1 Patrick MA Sleiman,1,2 Hakon Hakonarson1,2 1Center for Applied Genomics, Children's Hospital of Philadelphia Research Institute, 2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine. Keywords: asthma, genetics, GWAS, pharmacogenetics, biomarkers

  13. Association of diabetes mellitus and dementia : The Rotterdam study

    NARCIS (Netherlands)

    Ott, A; Stolk, RP; Hofman, A; vanHarskamp, F; Grobbee, DE; Breteler, MMB

    1996-01-01

    Dementia and non-insulin-dependent diabetes mellitus (NIDDM) are highly prevalent disorders in the elderly. Diabetes has repeatedly been reported to affect cognition, but its relation with dementia is uncertain. We therefore studied the association between diabetes and dementia in the Rotterdam

  14. 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

  15. Genomewide association study of body weight traits in Baluchi sheep

    Indian Academy of Sciences (India)

    2Faculty of Agronomy Sciences, Department of Animal Sciences, College of Agriculture and Natural Resources,. University of Tehran, Karaj 31587111674111, Iran. [Gholizadeh M., Rahimi-Mianji G. and Nejati-Javaremi A. 2015 Genomewide association study of body weight traits in Baluchi sheep. J. Genet. 94, 143–146].

  16. Factors associated with early adiposity rebound. ALSPAC Study Team.

    Science.gov (United States)

    Dorosty, A R; Emmett, P M; Cowin, S d; Reilly, J J

    2000-05-01

    The age at which body mass index (BMI) increases after its nadir in childhood, adiposity rebound (AR), is a critical period for the development of obesity. Children with early AR are at substantially increased risk of adult obesity. Few studies have examined the factors that influence the timing of the AR. The aims of this study were to test for influences on the timing of the AR, and to test the hypothesis that early AR is promoted by high-protein intake. Longitudinal cohort study of 889 children representative of the United Kingdom, followed from birth to 5 years. We tested for differences in dietary intake, parental BMI, socioeconomic status, and childhood BMI between 3 groups of children characterized by the following: very early AR (at or before 43 months), early AR (from 49 but before 61 months), and later AR (after 61 months). There was no evidence of associations between dietary protein intake, or any other dietary variable, and timing of the AR. Children with very early AR and early AR had parents with significantly higher BMI, and were significantly more likely to have at least 1 obese parent. This study does not support the hypothesis that early AR is promoted by high-protein intake. None of the dietary variables tested were significantly associated with timing of the AR, and timing of AR was not associated with socioeconomic status. Parental obesity was associated with an earlier AR.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  18. A Retrospective Study on Magnitude and Factors Associated with ...

    African Journals Online (AJOL)

    Background: Anemia in the postnatal period is a common problem, which has been subject of research recently. Though, it is a common problem, it is a less researched topic in India. Hence, this study was undertaken. Aim: The aim was to know the clinic.social factors associated with anemia in the postpartum period.

  19. Histological and morphometric studies on the age-associated ...

    African Journals Online (AJOL)

    Histological and morphometric studies on the age-associated changes in the colon of the mouse. MA Motabagani. Abstract. No Abstract. Journal of Experimental and Clinical Anatomy Vol. 5(1) 2006: 48-58. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  20. Study of Ventilator Associated Pneumonia in Neonatal Intensive ...

    African Journals Online (AJOL)

    Study of Ventilator Associated Pneumonia in Neonatal Intensive Care Unit: characteristics, risk factors and outcome. ... Most common bacterial isolated from endotracheal aspirate of VAP patients was Klebsiella spp (32.8%), E.coli (23.2%) and Acinetobacter (17.8%) being the other two common organisms. Very low birth ...

  1. Dental trauma in association with maxillofacial fractures: an epidemiological study

    NARCIS (Netherlands)

    Ruslin, M.; Wolff, J.; Boffano, P.; Brand, H.S.; Forouzanfar, T.

    2015-01-01

    Aim The aim of this study was to retrospectively investigate the incidence and associated factors of dental trauma in patients with maxillofacial fractures at the VU Medical Center in Amsterdam. Material and methods Data from 707 patients who were treated surgically for maxillofacial fractures were

  2. Dental trauma in association with maxillofacial fractures: an epidemiological study

    NARCIS (Netherlands)

    Ruslin, M.; Wolff, J.; Boffano, P.; Brand, H.S.; Forouzanfar, T.

    2015-01-01

    Aim: The aim of this study was to retrospectively investigate the incidence and associated factors of dental trauma in patients with maxillofacial fractures at the VU Medical Center in Amsterdam. Material and methods: Data from 707 patients who were treated surgically for maxillofacial fractures

  3. Molecular evaluation of genetic diversity and association studies in ...

    Indian Academy of Sciences (India)

    Molecular evaluation of genetic diversity and association studies in rice. (Oryza sativa L.) C. Vanniarajan, K. K. Vinod and Andy Pereira. J. Genet. 91, 9–19. Table 1. Chromosome-wise distribution of SSR alleles and their number (k), polymorphic information content (PIC) and allele discrimination index (Dm). Chromosome.

  4. Genome-Wide Association Study of Serum Selenium Concentrations

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    2013-05-01

    Full Text Available Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening and the Women’s Health Initiative (WHI. We tested association between 2,474,333 single nucleotide polymorphisms (SNPs and serum selenium concentrations using linear regression models. In the first stage (PLCO 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003 in the second stage (WHI. Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11 and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI. Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

  5. Genome association study of human chromosome 13 and ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 92; Issue 1. Genome association study of human chromosome 13 and susceptibility to coronary artery disease in a Chinese population. Peng Jie Chen Xing Li Tingting Xie Yi Zhang Jianning Jiang Tingting Liu Tianjiao Chen Gang Guo Yuan. Research Note Volume 92 Issue 1 ...

  6. Robust Association Tests for the Replication of Genome-Wide Association Studies.

    Science.gov (United States)

    Joo, Jungnam; Park, Ju-Hyun; Lee, Bora; Park, Boram; Kim, Sohee; Yoon, Kyong-Ah; Lee, Jin Soo; Geller, Nancy L

    2015-01-01

    In genome-wide association study (GWAS), robust genetic association tests such as maximum of three CATTs (MAX3), each corresponding to recessive, additive, and dominant genetic models, the minimum p value of Pearson's Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2), genetic model selection (GMS), and genetic model exclusion (GME) methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by p values of the discovery and replication studies.

  7. Robust Association Tests for the Replication of Genome-Wide Association Studies

    Directory of Open Access Journals (Sweden)

    Jungnam Joo

    2015-01-01

    Full Text Available In genome-wide association study (GWAS, robust genetic association tests such as maximum of three CATTs (MAX3, each corresponding to recessive, additive, and dominant genetic models, the minimum p value of Pearson’s Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2, genetic model selection (GMS, and genetic model exclusion (GME methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed by p values of the discovery and replication studies.

  8. Genome-wide association study of antisocial personality disorder.

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-09-06

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.

  9. Sample Size and Statistical Power Calculation in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Eun Pyo Hong

    2012-06-01

    Full Text Available A sample size with sufficient statistical power is critical to the success of genetic association studies to detect causal genes of human complex diseases. Genome-wide association studies require much larger sample sizes to achieve an adequate statistical power. We estimated the statistical power with increasing numbers of markers analyzed and compared the sample sizes that were required in case-control studies and case-parent studies. We computed the effective sample size and statistical power using Genetic Power Calculator. An analysis using a larger number of markers requires a larger sample size. Testing a single-nucleotide polymorphism (SNP marker requires 248 cases, while testing 500,000 SNPs and 1 million markers requires 1,206 cases and 1,255 cases, respectively, under the assumption of an odds ratio of 2, 5% disease prevalence, 5% minor allele frequency, complete linkage disequilibrium (LD, 1:1 case/control ratio, and a 5% error rate in an allelic test. Under a dominant model, a smaller sample size is required to achieve 80% power than other genetic models. We found that a much lower sample size was required with a strong effect size, common SNP, and increased LD. In addition, studying a common disease in a case-control study of a 1:4 case-control ratio is one way to achieve higher statistical power. We also found that case-parent studies require more samples than case-control studies. Although we have not covered all plausible cases in study design, the estimates of sample size and statistical power computed under various assumptions in this study may be useful to determine the sample size in designing a population-based genetic association study.

  10. Genome-wide association studies in nephrology: using known associations for data checks.

    Science.gov (United States)

    Wuttke, Matthias; Schaefer, Franz; Wong, Craig S; Köttgen, Anna

    2015-02-01

    Prior to conducting genome-wide association studies (GWAS) of renal traits and diseases, systematic checks to ensure data integrity and analytical work flow should be conducted. Using positive controls (ie, known associations between a single-nucleotide polymorphism [SNP] and a corresponding trait) allows for identifying errors that are not apparent solely from global evaluation of summary statistics. Strong genetic control associations of chronic kidney disease (CKD), as derived from GWAS, are lacking in the non-African ancestry CKD population; thus, in this perspective, we provide examples of and considerations for using positive controls among patients with CKD. Using data from individuals with CKD who participated in the CRIC (Chronic Renal Insufficiency Cohort) Study or PediGFR (Pediatric Investigation for Genetic Factors Linked to Renal Progression) Consortium, we evaluated 2 kinds of positive control traits: traits unrelated to kidney function (bilirubin level and body height) and those related to kidney function (cystatin C and urate levels). For the former, the proportion of variance in the control trait that is explained by the control SNP is the main determinant of the strength of the observable association, irrespective of adjustment for kidney function. For the latter, adjustment for kidney function can be effective in uncovering known associations among patients with CKD. For instance, in 1,092 participants in the PediGFR Consortium, the P value for the association of cystatin C concentrations and rs911119 in the CST3 gene decreased from 2.7×10(-3) to 2.4×10(-8) upon adjustment for serum creatinine-based estimated glomerular filtration rate. In this perspective, we give recommendations for the appropriate selection of control traits and SNPs that can be used for data checks prior to conducting GWAS among patients with CKD. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ildus I Ahmetov

    2014-10-01

    Full Text Available 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 (VO 2 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 <10 -5 -10 -8 between 218 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 VO 2 max both in males and females. Next, case-control studies resulted in remaining three SNPs ( NFIA-AS2 rs1572312, TSHR rs7144481, RBFOX1 rs7191721 associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of VO 2 max (males: P =0.0051; females: P =0.0005. Furthermore, the frequency of the rs1572312 C allele was significantly higher in elite endurance athletes (95.5% in comparison with non-elite endurance athletes (89.8%, P =0.0257, Russian (88.8%, P =0.007 and European (90.6%, P =0.0197 controls and power athletes (86.2%, P =0.0005. The rs1572312 SNP is located on the nuclear factor I A antisense RNA 2 ( NFIA-AS2 gene which is supposed to regulate the expression of the NFIA gene (encodes transcription factor involved in activation of erythropoiesis and repression of the granulopoiesis. Our data show that the NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 polymorphisms are associated with aerobic performance and elite endurance athlete status.

  12. Association between tobacco use in pregnancy and placenta-associated syndromes: a population-based study.

    Science.gov (United States)

    Aliyu, Muktar H; Lynch, O'Neil; Wilson, Ronee E; Alio, Amina P; Kristensen, Sibylle; Marty, Phillip J; Whiteman, Valerie E; Salihu, Hamisu M

    2011-04-01

    Cigarette smoking is an established risk factor for adverse perinatal outcomes. The purpose of this study is to examine the association between maternal smoking in pregnancy and the occurrence of placental-associated syndromes (PAS). We analyzed data from a population-based retrospective cohort of singleton deliveries that occurred in the state of Missouri from 1989 through 2005 (N = 1,224,133). The main outcome was PAS, a composite outcome defined as the occurrence of placental abruption, placenta previa, preeclampsia, small for gestational age, preterm or stillbirth. We used logistic regression models to generate adjusted odd ratios and their 95 percent confidence intervals. Non-smoking gravidas served as the referent category. The overall prevalence of prenatal smoking was 19.6%. Cigarette smoking in pregnancy was associated with the composite outcome of placental syndromes (odds ratio, 95% confidence interval = 1.59, 1.57-1.60). This association showed a dose-response relationship, with the risk of PAS increasing with increased quantity of cigarettes smoked. Similar results were observed between smoking in pregnancy and independent risks for abruption, previa, SGA, stillbirth, and preterm delivery. Maternal smoking in pregnancy is a risk factor for the development of placenta-associated syndrome. Smoking cessation interventions in pregnancy should continue to be encouraged in all maternity care settings.

  13. Association study between methylenetetrahydrofolate reductase gene polymorphisms and Graves' disease.

    Science.gov (United States)

    Mao, Renfang; Fan, Yihui; Zuo, Lulu; Geng, Dongfeng; Meng, Fantao; Zhu, Jing; Li, Qiang; Qiao, Hong; Jin, Yan; Bai, Jing; Fu, Songbin

    2010-10-01

    5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides, which are essential for DNA synthesis and methylation. It is highly polymorphic, and its variant genotypes result in lower enzymatic activity and higher plasma homocysteine. Previous studies have provided evidence that a high prevalence of MTHFR gene polymorphisms is frequently detected in patients with autoimmune disease, suggesting a novel genetic association with autoimmune disorders. However, the genetic association between MTHFR and Graves' disease (GD), one of the most common autoimmune diseases, has not been studied. Here, we designed a clinic-based case-control study including 199 GD cases and 235 healthy controls to examine the associations between three common MTHFR polymorphisms (i.e., C677T, A1298C, and G1793A) and GD. Surprisingly, logistic regression analysis shows MTHFR 677CT + TT genotypes are associated with an approximately 42% reduction in the risk of GD in women (adjusted OR = 0.58, 95% CI = 0.3-0.9), compared to the CC genotype, indicating a significant protective effect of 677CT + TT genotypes. Our result provides epidemiological evidence that MTHFR mutation (C677T) protects women from GD. The protective effect, possibly obtained by influencing DNA methylation, should be confirmed in a large number of cohorts. Copyright © 2010 John Wiley & Sons, Ltd.

  14. 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

  15. EHR-based phenome wide association study in pancreatic cancer.

    Science.gov (United States)

    Adamusiak, Tomasz; Shimoyama, Mary

    2014-01-01

    Pancreatic cancer is one of the most common causes of cancer-related deaths in the United States, it is difficult to detect early and typically has a very poor prognosis. We present a novel method of large-scale clinical hypothesis generation based on phenome wide association study performed using Electronic Health Records (EHR) in a pancreatic cancer cohort. The study population consisted of 1,154 patients diagnosed with malignant neoplasm of pancreas seen at The Froedtert & The Medical College of Wisconsin academic medical center between the years 2004 and 2013. We evaluated death of a patient as the primary clinical outcome and tested its association with the phenome, which consisted of over 2.5 million structured clinical observations extracted out of the EHR including labs, medications, phenotypes, diseases and procedures. The individual observations were encoded in the EHR using 6,617 unique ICD-9, CPT-4, LOINC, and RxNorm codes. We remapped this initial code set into UMLS concepts and then hierarchically expanded to support generalization into the final set of 10,164 clinical concepts, which formed the final phenome. We then tested all possible pairwise associations between any of the original 10,164 concepts and death as the primary outcome. After correcting for multiple testing and folding back (generalizing) child concepts were appropriate, we found 231 concepts to be significantly associated with death in the study population. With the abundance of structured EHR data, phenome wide association studies combined with knowledge engineering can be a viable method of rapid hypothesis generation.

  16. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Qiong Yang

    2012-01-01

    Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

  17. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects.

    Science.gov (United States)

    Ramachandran, Dhanya; Zeng, Zhen; Locke, Adam E; Mulle, Jennifer G; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford L; Capone, George T; Reeves, Roger H; Maslen, Cheryl L; Cutler, David J; Feingold, Eleanor; Sherman, Stephanie L; Zwick, Michael E

    2015-07-20

    The goal of this study was to identify the contribution of common genetic variants to Down syndrome-associated atrioventricular septal defect, a severe heart abnormality. Compared with the euploid population, infants with Down syndrome, or trisomy 21, have a 2000-fold increased risk of presenting with atrioventricular septal defects. The cause of this increased risk remains elusive. Here we present data from the largest heart study conducted to date on a trisomic background by using a carefully characterized collection of individuals from extreme ends of the phenotypic spectrum. We performed a genome-wide association study using logistic regression analysis on 452 individuals with Down syndrome, consisting of 210 cases with complete atrioventricular septal defects and 242 controls with structurally normal hearts. No individual variant achieved genome-wide significance. We identified four disomic regions (1p36.3, 5p15.31, 8q22.3, and 17q22) and two trisomic regions on chromosome 21 (around PDXK and KCNJ6 genes) that merit further investigation in large replication studies. Our data show that a few common genetic variants of large effect size (odds ratio >2.0) do not account for the elevated risk of Down syndrome-associated atrioventricular septal defects. Instead, multiple variants of low-to-moderate effect sizes may contribute to this elevated risk, highlighting the complex genetic architecture of atrioventricular septal defects even in the highly susceptible Down syndrome population. Copyright © 2015 Ramachandran et al.

  18. Genetic association study of synphilin-1 in idiopathic Parkinson's disease

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    Farrer Matthew J

    2008-03-01

    Full Text Available Abstract Background Post-mortem Lewy body and Lewy neuritic inclusions are a defining feature of Parkinson's disease (PD and dementia with Lewy bodies (DLB. With the discovery of missense and multiplication mutations in the alpha-synuclein gene (SNCA in familial parkinsonism, Lewy inclusions were found to stain intensely with antibodies raised against the protein. Yeast-two-hybrid studies identified synphilin-1 as an interacting partner of alpha-synuclein, and both proteins show co-immunolocalization in a subset of Lewy body inclusions. In the present study, we have investigated whether common variability in synphilin-1, including coding substitutions are genetically associated with disease pathogenesis. Methods We screened the synphilin-1 gene for 11 single nucleotide polymorphisms (SNPs in 300 affected subjects with idiopathic Parkinson's disease and 412 healthy controls. Six of these were rare variants including five previously identified amino acid substitutions that were chosen in a direct approach for association of rare disease causing mutations. An additional five highly heterozygous SNPs were chosen for an indirect association approach including haplotype analysis, based on the assumption that any disease causing mutations might be in linkage disequilibrium with the SNPs selected. We also genotyped a microsatellite marker (D5S2950 within intron 6 of the gene and five additional microsatellites clustered downstream of the 5p23.1-23.3 synphilin-1 locus. Genome-wide linkage analysis, in a number of independent studies, has previously highlighted suggestive linkage to PD in this region of chromosome 5. Results Screening of previously known amino acid substitutions in the synphilin-1 gene, identified the C1861>T (R621C substitution in four patients (chromosomes n = 600 and 10 control subjects (chromosomes n = 824, whereas the G2125>C (E706Q substitution was detected in one patient and four control subject, suggesting both these substitutions

  19. Liposomes- and ethosomes-associated distamycins: a comparative study.

    Science.gov (United States)

    Cortesi, Rita; Romagnoli, Romeo; Drechsler, Markus; Menegatti, Enea; Zaid, Abdel N; Ravani, Laura; Esposito, Elisabetta

    2010-12-01

    The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration.

  20. Genome-wide association study of sporadic brain arteriovenous malformations.

    Science.gov (United States)

    Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G; Sidney, Stephen; McCulloch, Charles E; Al-Shahi Salman, Rustam; Berg, Jonathan N; Koeleman, Bobby P C; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto; Puca, Alfredo; Lawton, Michael T; Young, William L; Pawlikowska, Ludmila; Klijn, Catharina J M; Kim, Helen

    2016-09-01

    The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with pJAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. 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/

  1. Association study of 182 candidate genes in anorexia nervosa.

    Science.gov (United States)

    Pinheiro, Andrea Poyastro; Bulik, Cynthia M; Thornton, Laura M; Sullivan, Patrick F; Root, Tammy L; Bloss, Cinnamon S; Berrettini, Wade H; Schork, Nicholas J; Kaye, Walter H; Bergen, Andrew W; Magistretti, Pierre; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M; Goldman, David; Halmi, Katherine A; Johnson, Craig; Kaplan, Allan S; Keel, Pamela K; Klump, Kelly L; La Via, Maria; Mitchell, James E; Strober, Michael; Rotondo, Alessandro; Treasure, Janet; Woodside, D Blake

    2010-07-01

    We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case-control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN. (c) 2010 Wiley-Liss, Inc.

  2. 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......, 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....

  3. Aortic aneurysm association with SLE - a case-control study.

    Science.gov (United States)

    Guy, A; Tiosano, S; Comaneshter, D; Tekes-Manova, D; Shovman, O; Cohen, A D; Amital, H

    2016-08-01

    Aortic aneurysm is a life threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE).The purpose of this study was to investigate the association between SLE and occurrence of aortic aneurysms. Patients with SLE were compared with age- and sex-matched controls regarding the proportion of aortic aneurysm in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The proportion of aortic aneurysm in patients with SLE was increased compared with the proportion in controls (0.6% and 0.1%, respectively, p SLE was associated with the coexistence of aortic aneurysms (odds ratio 2.06, 95% confidence interval 1.21-3.51). Patients with SLE have a higher proportion of aortic aneurysms as compared with matched controls. Therefore, physicians treating patients with SLE should be aware of this life threatening association. © The Author(s) 2016.

  4. Association studies in common endocrine diseases (review article

    Directory of Open Access Journals (Sweden)

    Akrami SM

    2007-05-01

    Full Text Available Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

  5. Genome-wide association study of pathological gambling.

    Science.gov (United States)

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

    2016-08-01

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

  6. Translating genome wide association study results to associations among common diseases: in silico study with an electronic medical record.

    Science.gov (United States)

    Anand, Vibha; Rosenman, Marc B; Downs, Stephen M

    2013-09-01

    To develop a map of disease associations exclusively using two publicly available genetic sources: the catalog of single nucleotide polymorphisms (SNPs) from the HapMap, and the catalog of Genome Wide Association Studies (GWAS) from the NHGRI, and to evaluate it with a large, long-standing electronic medical record (EMR). A computational model, In Silico Bayesian Integration of GWAS (IsBIG), was developed to learn associations among diseases using a Bayesian network (BN) framework, using only genetic data. The IsBIG model (I-Model) was re-trained using data from our EMR (M-Model). Separately, another clinical model (C-Model) was learned from this training dataset. The I-Model was compared with both the M-Model and the C-Model for power to discriminate a disease given other diseases using a test dataset from our EMR. Area under receiver operator characteristics curve was used as a performance measure. Direct associations between diseases in the I-Model were also searched in the PubMed database and in classes of the Human Disease Network (HDN). On the basis of genetic information alone, the I-Model linked a third of diseases from our EMR. When compared to the M-Model, the I-Model predicted diseases given other diseases with 94% specificity, 33% sensitivity, and 80% positive predictive value. The I-Model contained 117 direct associations between diseases. Of those associations, 20 (17%) were absent from the searches of the PubMed database; one of these was present in the C-Model. Of the direct associations in the I-Model, 7 (35%) were absent from disease classes of HDN. Using only publicly available genetic sources we have mapped associations in GWAS to a human disease map using an in silico approach. Furthermore, we have validated this disease map using phenotypic data from our EMR. Models predicting disease associations on the basis of known genetic associations alone are specific but not sensitive. Genetic data, as it currently exists, can only explain a fraction

  7. Association of Torsion With Testicular Cancer: A Retrospective Study.

    Science.gov (United States)

    Uguz, Sami; Yilmaz, Sercan; Guragac, Ali; Topuz, Bahadır; Aydur, Emin

    2016-02-01

    Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported with the association of torsion in surgical specimens, and the published data remain scant on the association of torsion with testicular tumors. By retrospective medical record review, we identified 32 patients who had been diagnosed with testicular torsion, 20 of whom had undergone orchiectomy. Of these 20 patients, 2 were diagnosed with a malignancy. Our study, the largest case series to date, has shown an association between testicular torsion and testicular cancer of 6.4%. Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported in association with torsion in surgical specimens. However, the published data remain scant on the association between torsion and the presence of testicular tumors. The present retrospective study explored the association between torsion and testicular cancer in patients with testicular torsion undergoing orchiectomy during scrotal exploration. A medical record review was performed of patients who had had a diagnosis of testicular torsion from January 2003 to February 2015. The clinicopathologic characteristics of the patients were recorded. A total of 32 patients were identified. Their mean age was 21.1 years (range, 7-39 years). All the patients had unilateral testicular torsion, which affected the left side in 17 and the right side in 15. Manual detorsion was successful in 6 patients, and 26 patients underwent emergency surgery with testicular detorsion (6 fixation surgery and 20 orchiectomy). The type of incision was scrotal in 6, inguinal in 10, and unspecified in 4. Pathologic examination of the orchiectomy specimens showed malignancy in 2 cases (seminoma and malign mixed germ cell tumor). To the best of our knowledge, the present single-center case series is the largest case series to date of

  8. Disease-Concordant Twins Empower Genetic Association Studies

    DEFF Research Database (Denmark)

    Tan, Qihua; Li, Weilong; Vandin, Fabio

    2017-01-01

    concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases...... of an ordinary case-control design, with variations depending on genetic mode. Importantly, the enriched power for dizygotic twins also applies to disease-concordant sibling pairs, which largely extends the application of the concordant twin design. Overall, our simulation revealed a high value of disease......-concordant twins in genetic association studies and encourages the use of genetically related individuals for highly efficiently identifying both common and rare genetic variants underlying human complex diseases without increasing laboratory cost....

  9. Bayesian neural networks for detecting epistasis in genetic association studies.

    Science.gov (United States)

    Beam, Andrew L; Motsinger-Reif, Alison; Doyle, Jon

    2014-11-21

    Discovering causal genetic variants from large genetic association studies poses many difficult challenges. Assessing which genetic markers are involved in determining trait status is a computationally demanding task, especially in the presence of gene-gene interactions. A non-parametric Bayesian approach in the form of a Bayesian neural network is proposed for use in analyzing genetic association studies. Demonstrations on synthetic and real data reveal they are able to efficiently and accurately determine which variants are involved in determining case-control status. By using graphics processing units (GPUs) the time needed to build these models is decreased by several orders of magnitude. In comparison with commonly used approaches for detecting interactions, Bayesian neural networks perform very well across a broad spectrum of possible genetic relationships. The proposed framework is shown to be a powerful method for detecting causal SNPs while being computationally efficient enough to handle large datasets.

  10. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  11. 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

    2017-02-01

    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. A validated algorithm identified RA subjects from the de-identified version of the Vanderbilt University Medical Center EHR. Serotypes were determined by rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) values. We tested EHR-derived phenotypes using PheWAS comparing seropositive RA and seronegative RA, yielding disease associations. PheWAS was also performed in 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. A total of 2,199 RA individuals with either RF or ACPA testing were identified. Of these, 1,382 patients (63%) were classified as seropositive. Seronegative RA was associated with myalgia and myositis (odds ratio [OR] 2.1, P = 3.7 × 10-10 ) and back pain. A manual review of the health record showed that among subjects coded for Myalgia and Myositis, ∼80% had fibromyalgia. 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 ). This PheWAS of RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity and chronic airway obstruction and between seropositivity and tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease. © 2016, American College of Rheumatology.

  12. [Factors associated with contacting HIV/AIDS associations in Ecuador: results of a community study].

    Science.gov (United States)

    Bernier, Adeline; Acosta, María Elena; Castro, Daniela Rojas; Bonifaz, Cesar; Jaramillo, Santiago; Henry, Emilie; Otis, Joanne; Préau, Marie

    2015-09-01

    To describe the profile of people living with HIV/AIDS (PLHA) who contact HIV/AIDS associations in Ecuador and to identify the factors related to that contact. In 2011, a cross-sectional community study was conducted in two hospitals in Guayaquil. Based on a 125-question survey administered to 300 adult PLHA, a weighted multivariate regression analysis was performed to identify the factors related to contact with an association Of the 300 participants, 34 (11.3%) were in contact with an association. Being over the age of 35, scoring high on the self-efficacy scale, having suffered serious social consequences after disclosing their HIV status, being able to talk to friends about living with HIV, expressing the need to talk about living with HIV with a health professional, and scoring low on the index of the HIV status disclosure control effort were related to that contact. The characteristics of the PLHA in contact with an association were: being over the age of 35, having suffered serious social consequences following disclosure of seropositivity, and feeling that their psychosocial needs were not being met by the health system in terms of the services provided. These people more easily managed their HIV status in their social milieu and displayed a greater ability to talk to friends about their seropositivity. This information is useful for community actors to maintain and support mobilization on HIV in Ecuador.

  13. Genome-Wide Association Study Identifies Candidate Loci Associated with Platelet Count in Koreans

    Directory of Open Access Journals (Sweden)

    Ji Hee Oh

    2014-12-01

    Full Text Available Platelets are derived from the fragments that are formed from the cytoplasm of bone marrow megakaryocytes-small irregularly shaped anuclear cells. Platelets respond to vascular damage, contracts blood vessels, and attaches to the damaged region, thereby stopping bleeding, together with the action of blood coagulation factors. Platelet activation is known to affect genes associated with vascular risk factors, as well as with arteriosclerosis and myocardial infarction. Here, we performed a genome-wide association study with 352,228 single-nucleotide polymorphisms typed in 8,842 subjects of the Korea Association Resource (KARE project and replicated the results in 7,861 subjects from an independent population. We identified genetic associations between platelet count and common variants nearby chromosome 4p16.1 (p = 1.46 × 10-10, in the KIAA0232 gene, 6p21 (p = 1.36 × 10-7, in the BAK1 gene, and 12q24.12 (p = 1.11 × 10-15, in the SH2B3 gene. Our results illustrate the value of large-scale discovery and a focus for several novel research avenues.

  14. Transethnic Meta-Analysis of Genomewide Association Studies

    OpenAIRE

    Morris, Andrew P.

    2011-01-01

    The detection of loci contributing effects to complex human traits, and their subsequent fine-mapping for the location of causal variants, remains a considerable challenge for the genetics research community. Meta-analyses of genomewide association studies, primarily ascertained from European-descent populations, have made considerable advances in our understanding of complex trait genetics, although much of their heritability is still unexplained. With the increasing availability of genomewi...

  15. Facial dermatosis associated with Demodex: a case-control study*

    OpenAIRE

    Zhao, Ya-e; Peng, Yan; Wang, Xiang-lan; Wu, Li-ping; Wang, Mei; Yan, Hu-ling; Xiao, Sheng-Xiang

    2011-01-01

    Demodex has been considered to be related with multiple skin disorders, but controversy persists. In this case-control study, a survey was conducted with 860 dermatosis patients aged 12 to 84 years in Xi’an, China to identify the association between facial dermatosis and Demodex. Amongst the patients, 539 suffered from facial dermatosis and 321 suffered from non-facial dermatosis. Demodex mites were sampled and examined using the skin pressurization method. Multivariate regression analysis wa...

  16. Study clarifies associations between hypogonadism and health in aging men.

    Science.gov (United States)

    Amory, John K

    2012-11-01

    Tajar and colleagues present the associations between moderate and severe hypogonadism, symptoms of androgen deficiency and the prevelence of end-organ evidence of androgen deficency in 2966 older men in the European Male Aging Study. They find lower muscle mass, reduced bone mineral density, anemia, insulin resistence, metabolic syndrome and cardiovascular disease, with greater risks of these signs of androgen deficiency at lower serum testosterone concentrations.

  17. Dental trauma in association with maxillofacial fractures: an epidemiological study

    OpenAIRE

    Ruslin, Muhammad

    2015-01-01

    The aim of this study was to retrospectively investigate the incidence and associated factors of dental trauma in patients with maxillofacial fractures at the VU Medical Center in Amsterdam. Material and methods: Data from 707 patients who were treated surgically for maxillofacial fractures were evaluated. The data were collected retrospectively from patient files and other available databases. The data collected included date of fracture, age, gender, type of fracture, and ...

  18. Lipid nanotechnologies for structural studies of membrane-associated proteins.

    Science.gov (United States)

    Stoilova-McPhie, Svetla; Grushin, Kirill; Dalm, Daniela; Miller, Jaimy

    2014-11-01

    We present a methodology of lipid nanotubes (LNT) and nanodisks technologies optimized in our laboratory for structural studies of membrane-associated proteins at close to physiological conditions. The application of these lipid nanotechnologies for structure determination by cryo-electron microscopy (cryo-EM) is fundamental for understanding and modulating their function. The LNTs in our studies are single bilayer galactosylceramide based nanotubes of ∼20 nm inner diameter and a few microns in length, that self-assemble in aqueous solutions. The lipid nanodisks (NDs) are self-assembled discoid lipid bilayers of ∼10 nm diameter, which are stabilized in aqueous solutions by a belt of amphipathic helical scaffold proteins. By combining LNT and ND technologies, we can examine structurally how the membrane curvature and lipid composition modulates the function of the membrane-associated proteins. As proof of principle, we have engineered these lipid nanotechnologies to mimic the activated platelet's phosphtaidylserine rich membrane and have successfully assembled functional membrane-bound coagulation factor VIII in vitro for structure determination by cryo-EM. The macromolecular organization of the proteins bound to ND and LNT are further defined by fitting the known atomic structures within the calculated three-dimensional maps. The combination of LNT and ND technologies offers a means to control the design and assembly of a wide range of functional membrane-associated proteins and complexes for structural studies by cryo-EM. The presented results confirm the suitability of the developed methodology for studying the functional structure of membrane-associated proteins, such as the coagulation factors, at a close to physiological environment. © 2014 Wiley Periodicals, Inc.

  19. Blunt abdominal aortic injury: a Western Trauma Association multicenter study.

    Science.gov (United States)

    Shalhub, Sherene; Starnes, Benjamin W; Brenner, Megan L; Biffl, Walter L; Azizzadeh, Ali; Inaba, Kenji; Skiada, Dimitra; Zarzaur, Ben; Nawaf, Cayce; Eriksson, Evert A; Fakhry, Samir M; Paul, Jasmeet S; Kaups, Krista L; Ciesla, David J; Todd, S Rob; Seamon, Mark J; Capano-Wehrle, Lisa M; Jurkovich, Gregory J; Kozar, Rosemary A

    2014-12-01

    Blunt abdominal aortic injury (BAAI) is a rare injury. The objective of the current study was to examine the presentation and management of BAAI at a multi-institutional level. The Western Trauma Association Multi-Center Trials conducted a study of BAAI from 1996 to 2011. Data collected included demographics, injury mechanism, associated injuries, interventions, and complications. Of 392,315 blunt trauma patients, 113 (0.03%) presented with BAAI at 12 major trauma centers (67% male; median age, 38 years; range, 6-88; median Injury Severity Score [ISS], 34; range, 16-75). The leading cause of injury was motor vehicle collisions (60%). Hypotension was documented in 47% of the cases. The most commonly associated injuries were spine fractures (44%) and pneumothorax/hemothorax (42%). Solid organ, small bowel, and large bowel injuries occurred in 38%, 35%, and 28% respectively. BAAI presented as free aortic rupture (32%), pseudoaneurysm (16%), and injuries without aortic external contour abnormality on computed tomography such as large intimal flaps (34%) or intimal tears (18%). Open and endovascular repairs were undertaken as first-choice therapy in 43% and 15% of cases, respectively. Choice of management varied by type of BAAI: 89% of intimal tears were managed nonoperatively, and 96% of aortic ruptures were treated with open repair. Overall mortality was 39%, the majority (68%) occurring in the first 24 hours because of hemorrhage or cardiac arrest. The highest mortality was associated with Zone II aortic ruptures (92%). Follow-up was documented in 38% of live discharges. This is the largest BAAI series reported to date. BAAI presents as a spectrum of injury ranging from minimal aortic injury to aortic rupture. Nonoperative management is successful in uncomplicated cases without external aortic contour abnormality on computed tomography. Highest mortality occurred in free aortic ruptures, suggesting that alternative measures of early noncompressible torso hemorrhage

  20. Association of DNA Methylation Differences With Schizophrenia in an Epigenome-Wide Association Study.

    Science.gov (United States)

    Montano, Carolina; Taub, Margaret A; Jaffe, Andrew; Briem, Eirikur; Feinberg, Jason I; Trygvadottir, Rakel; Idrizi, Adrian; Runarsson, Arni; Berndsen, Birna; Gur, Ruben C; Moore, Tyler M; Perry, Rodney T; Fugman, Doug; Sabunciyan, Sarven; Yolken, Robert H; Hyde, Thomas M; Kleinman, Joel E; Sobell, Janet L; Pato, Carlos N; Pato, Michele T; Go, Rodney C; Nimgaonkar, Vishwajit; Weinberger, Daniel R; Braff, David; Gur, Raquel E; Fallin, Margaret Daniele; Feinberg, Andrew P

    2016-05-01

    DNA methylation may play an important role in schizophrenia (SZ), either directly as a mechanism of pathogenesis or as a biomarker of risk. To scan genome-wide DNA methylation data to identify differentially methylated CpGs between SZ cases and controls. Epigenome-wide association study begun in 2008 using DNA methylation levels of 456 513 CpG loci measured on the Infinium HumanMethylation450 array (Illumina) in a consortium of case-control studies for initial discovery and in an independent replication set. Primary analyses used general linear regression, adjusting for age, sex, race/ethnicity, smoking, batch, and cell type heterogeneity. The discovery set contained 689 SZ cases and 645 controls (n = 1334), from 3 multisite consortia: the Consortium on the Genetics of Endophenotypes in Schizophrenia, the Project among African-Americans To Explore Risks for Schizophrenia, and the Multiplex Multigenerational Family Study of Schizophrenia. The replication set contained 247 SZ cases and 250 controls (n = 497) from the Genomic Psychiatry Cohort. Identification of differentially methylated positions across the genome in SZ cases compared with controls. Of the 689 case participants in the discovery set, 477 (69%) were men and 258 (37%) were non-African American; of the 645 controls, 273 (42%) were men and 419 (65%) were non-African American. In our replication set, cases/controls were 76% male and 100% non-African American. We identified SZ-associated methylation differences at 923 CpGs in the discovery set (false discovery rate, <0.2). Of these, 625 showed changes in the same direction including 172 with P < .05 in the replication set. Some replicated differentially methylated positions are located in a top-ranked SZ region from genome-wide association study analyses. This analysis identified 172 replicated new associations with SZ after careful correction for cell type heterogeneity and other potential confounders. The overlap with previous genome

  1. Genome-Wide Association Study of Antiphospholipid Antibodies

    Directory of Open Access Journals (Sweden)

    M. Ilyas Kamboh

    2013-01-01

    Full Text Available Background. The persistent presence of antiphospholipid antibodies (APA may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL, lupus anticoagulant (LAC, and anti-β2 glycoprotein I antibodies (anti-β2GPI. Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs. Association of SNPs with the antibody status (positive/negative was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with Passociations of HLA genes and APOH with APA but these were not the top loci. Conclusions. We have identified a number of suggestive novel loci for APA that will stimulate follow-up studies in independent and larger samples to replicate our findings.

  2. A Pooled Genome-Wide Association Study of Asperger Syndrome.

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    Varun Warrier

    Full Text Available Asperger Syndrome (AS is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC, which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448 were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448 lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  3. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Science.gov (United States)

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  4. Significance of genome-wide association studies in molecular anthropology.

    Science.gov (United States)

    Gupta, Vipin; Khadgawat, Rajesh; Sachdeva, Mohinder Pal

    2009-12-01

    The successful advent of a genome-wide approach in association studies raises the hopes of human geneticists for solving a genetic maze of complex traits especially the disorders. This approach, which is replete with the application of cutting-edge technology and supported by big science projects (like Human Genome Project; and even more importantly the International HapMap Project) and various important databases (SNP database, CNV database, etc.), has had unprecedented success in rapidly uncovering many of the genetic determinants of complex disorders. The magnitude of this approach in the genetics of classical anthropological variables like height, skin color, eye color, and other genome diversity projects has certainly expanded the horizons of molecular anthropology. Therefore, in this article we have proposed a genome-wide association approach in molecular anthropological studies by providing lessons from the exemplary study of the Wellcome Trust Case Control Consortium. We have also highlighted the importance and uniqueness of Indian population groups in facilitating the design and finding optimum solutions for other genome-wide association-related challenges.

  5. Pathway analysis comparison using Crohn's disease genome wide association studies.

    Science.gov (United States)

    Ballard, David; Abraham, Clara; Cho, Judy; Zhao, Hongyu

    2010-06-28

    The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest. We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test) based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype. Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways. Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.

  6. Pathway analysis comparison using Crohn's disease genome wide association studies

    Directory of Open Access Journals (Sweden)

    Cho Judy

    2010-06-01

    Full Text Available Abstract Background The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest. Methods We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype. Results Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways. Conclusions Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.

  7. Adult Learning Open University Determinants (ALOUD) study: Psychological factors associated with study success

    NARCIS (Netherlands)

    Neroni, Joyce; De Groot, Renate; Kirschner, Paul A.

    2013-01-01

    Neroni, J., De Groot, R. H. M., & Kirschner, P. A. (2012, 7 November). Adult Learning Open University Determinants (ALOUD) study: Psychological factors associated with study success. Poster presentation at the International ICO Fall School, Girona, Spain.

  8. Adult Learning Open University Determinants study (ALOUD): Biological lifestyle factors associated with study success

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2012-01-01

    Gijselaers, H. J. M., De Groot, R. H. M., & Kirschner, P. A. (2012, 7 November). Adult Learning Open University Determinants study (ALOUD): Biological lifestyle factors associated with study success. Poster presentation at the International ICO Fall School, Girona, Spain.

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

    Directory of Open Access Journals (Sweden)

    Estelle Dumas-Mallet

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

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

  12. Multiethnic genetic association studies improve power for locus discovery.

    Directory of Open Access Journals (Sweden)

    Sara L Pulit

    2010-09-01

    Full Text Available To date, genome-wide association studies have focused almost exclusively on populations of European ancestry. These studies continue with the advent of next-generation sequencing, designed to systematically catalog and test low-frequency variation for a role in disease. A complementary approach would be to focus further efforts on cohorts of multiple ethnicities. This leverages the idea that population genetic drift may have elevated some variants to higher allele frequency in different populations, boosting statistical power to detect an association. Based on empirical allele frequency distributions from eleven populations represented in HapMap Phase 3 and the 1000 Genomes Project, we simulate a range of genetic models to quantify the power of association studies in multiple ethnicities relative to studies that exclusively focus on samples of European ancestry. In each of these simulations, a first phase of GWAS in exclusively European samples is followed by a second GWAS phase in any of the other populations (including a multiethnic design. We find that nontrivial power gains can be achieved by conducting future whole-genome studies in worldwide populations, where, in particular, African populations contribute the largest relative power gains for low-frequency alleles (<5% of moderate effect that suffer from low power in samples of European descent. Our results emphasize the importance of broadening genetic studies to worldwide populations to ensure efficient discovery of genetic loci contributing to phenotypic trait variability, especially for those traits for which large numbers of samples of European ancestry have already been collected and tested.

  13. INFECTIOUS KERATITIS-ASSOCIATED ENDOPHTHALMITIS: A 14-Year Study.

    Science.gov (United States)

    Malihi, Mehrdad; Li, Xintong; Patel, Shriji; Eck, Thomas; Chu, David S; Zarbin, Marco A; Bhagat, Neelakshi

    2017-04-01

    To describe the demographics, characteristics, management, and outcomes of eyes with endophthalmitis related to infectious keratitis. Retrospective chart review of all patients treated for infectious keratitis-associated infectious endophthalmitis between 2001 and 2014 at University Hospital, Rutgers New Jersey Medical School. Thirty-eight cases with infectious keratitis-associated infectious endophthalmitis were identified (21 men [55%], mean age: 66.2 ± 20.7 years), with average time from the beginning of ulcer symptoms to endophthalmitis of 11.0 days. Associated systemic conditions (diabetes, HIV, immunosuppressive therapy, cirrhosis, or dementia) were present in 57.9%; 60.5% had previous intraocular surgery. Etiology showed gram-positive bacteria in 14 cases (36.9%), gram-negative bacteria in 7 (18.4%), fungi in 4 (10.5%), and no growth/unknown in 12 (31.6%). Nineteen cases (50%) presented with no light perception and were primarily enucleated. The remaining 19 eyes each received intravitreal antibiotics (mean: 1.5 injections); 8 (42.0%) underwent pars plans vitrectomy with vitreous biopsy, whereas 5 (26.3%) received emergency corneal transplantation. Final visual acuity was no light perception in 6 eyes (3 secondarily enucleated), light perception in 2, hand motion in 7, counting fingers in 2, and ≥20/50 in 2. Our study of 38 eyes with infectious keratitis-associated infectious endophthalmitis revealed generally poor visual outcomes and a high rate of systemic conditions and previous intraocular surgery.

  14. Mixture model-based association analysis with case-control data in genome wide association studies.

    Science.gov (United States)

    Ali, Fadhaa; Zhang, Jian

    2017-07-26

    Multilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.

  15. Genome-wide association study of antisocial personality disorder

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-01-01

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53–3.14), P=1.9 × 10-5). Two polymorphisms at 6p21.2 LINC00951–LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37–1.85), P=1.6 × 10−9) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder. PMID:27598967

  16. Design considerations for genetic linkage and association studies.

    Science.gov (United States)

    Nsengimana, Jérémie; Bishop, D Timothy

    2012-01-01

    This chapter describes the main issues that genetic epidemiologists usually consider in the design of linkage and association studies. For linkage, we briefly consider the situation of rare, highly penetrant alleles showing a disease pattern consistent with Mendelian inheritance investigated through parametric methods in large pedigrees or with autozygosity mapping in inbred families, and we then turn our focus to the most common design, affected sibling pairs, of more relevance for common, complex diseases. Theoretical and more practical power and sample size calculations are provided as a function of the strength of the genetic effect being investigated. We also discuss the impact of other determinants of statistical power such as disease heterogeneity, pedigree, and genotyping errors, as well as the effect of the type and density of genetic markers. Linkage studies should be as large as possible to have sufficient power in relation to the expected genetic effect size. Segregation analysis, a formal statistical technique to describe the underlying genetic susceptibility, may assist in the estimation of the relevant parameters to apply, for instance. However, segregation analyses estimate the total genetic component rather than a single-locus effect. Locus heterogeneity should be considered when power is estimated and at the analysis stage, i.e. assuming smaller locus effect than the total the genetic component from segregation studies. Disease heterogeneity should be minimised by considering subtypes if they are well defined or by otherwise collecting known sources of heterogeneity and adjusting for them as covariates; the power will depend upon the relationship between the disease subtype and the underlying genotypes. Ultimately, identifying susceptibility alleles of modest effects (e.g. RR≤1.5) requires a number of families that seem unfeasible in a single study. Meta-analysis and data pooling between different research groups can provide a sizeable study

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

    Science.gov (United States)

    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

    2016-03-01

    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 meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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

    Science.gov (United States)

    Cichon, Sven; Craddock, Nick; Daly, Mark; Faraone, Stephen V; Gejman, Pablo V; Kelsoe, John; Lehner, Thomas; Levinson, Douglas F; Moran, Audra; Sklar, Pamela; Sullivan, Patrick F

    2009-05-01

    The authors conducted a review of the history and empirical basis of genomewide association studies (GWAS), the rationale for GWAS of psychiatric disorders, results to date, limitations, and plans for GWAS meta-analyses. A literature review was carried out, power and other issues discussed, and planned studies assessed. Most of the genomic DNA sequence differences between any two people are common (frequency >5%) single nucleotide polymorphisms (SNPs). Because of localized patterns of correlation (linkage disequilibrium), 500,000 to 1,000,000 of these SNPs can test the hypothesis that one or more common variants explain part of the genetic risk for a disease. GWAS technologies can also detect some of the copy number variants (deletions and duplications) in the genome. Systematic study of rare variants will require large-scale resequencing analyses. GWAS methods have detected a remarkable number of robust genetic associations for dozens of common diseases and traits, leading to new pathophysiological hypotheses, although only small proportions of genetic variance have been explained thus far and therapeutic applications will require substantial further effort. Study design issues, power, and limitations are discussed. For psychiatric disorders, there are initial significant findings for common SNPs and for rare copy number variants, and many other studies are in progress. GWAS of large samples have detected associations of common SNPs and of rare copy number variants with psychiatric disorders. More findings are likely, since larger GWAS samples detect larger numbers of common susceptibility variants, with smaller effects. The Psychiatric GWAS Consortium is conducting GWAS meta-analyses for schizophrenia, bipolar disorder, major depressive disorder, autism, and attention deficit hyperactivity disorder. Based on results for other diseases, larger samples will be required. The contribution of GWAS will depend on the true genetic architecture of each disorder.

  19. An efficient empirical Bayes method for genomewide association studies.

    Science.gov (United States)

    Wang, Q; Wei, J; Pan, Y; Xu, S

    2016-08-01

    Linear mixed model (LMM) is one of the most popular methods for genomewide association studies (GWAS). Numerous forms of LMM have been developed; however, there are two major issues in GWAS that have not been fully addressed before. The two issues are (i) the genomic background noise and (ii) low statistical power after Bonferroni correction. We proposed an empirical Bayes (EB) method by assigning each marker effect a normal prior distribution, resulting in shrinkage estimates of marker effects. We found that such a shrinkage approach can selectively shrink marker effects and reduce the noise level to zero for majority of non-associated markers. In the meantime, the EB method allows us to use an 'effective number of tests' to perform Bonferroni correction for multiple tests. Simulation studies for both human and pig data showed that EB method can significantly increase statistical power compared with the widely used exact GWAS methods, such as GEMMA and FaST-LMM-Select. Real data analyses in human breast cancer identified improved detection signals for markers previously known to be associated with breast cancer. We therefore believe that EB method is a valuable tool for identifying the genetic basis of complex traits. © 2015 Blackwell Verlag GmbH.

  20. Genome-Wide Association Studies of Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Mayumi Tamari

    2013-01-01

    Full Text Available Allergic diseases are complex diseases caused by a combination of genetic and environmental factors. To determine the genetic components of these diseases and to discover the genes and cellular pathways underlying them, a large number of genetic studies have been conducted. Progress in genetics enables us to conduct genome-wide association studies (GWASs, which is a comprehensive and unbiased approach to identify susceptibility loci for multifactorial diseases. Recent GWASs have convincingly detected a large number of loci associated with allergic diseases. Candidate genes in the susceptibility loci suggest roles for epithelial barrier functions, innate-adaptive immunity, IL-1 family signaling, regulatory T cells and the vitamin D pathway in the pathogenesis of allergic diseases. Interestingly, the IL1RL1, HLA, IL13 and C11orf30 regions are overlapping susceptibility loci among atopic dermatitis and asthma or allergic rhinitis. Although a more complete collection of associated genes and pathways is needed, biologic insights revealed by GWASs improve our understanding of the pathophysiology of human allergic diseases and contribute to the development of better treatment and preventive strategies.

  1. Genetic Association Study of KCNQ5 Polymorphisms with High Myopia

    Directory of Open Access Journals (Sweden)

    Xuan Liao

    2017-01-01

    Full Text Available Identification of genetic variations related to high myopia may advance our knowledge of the etiopathogenesis of refractive error. This study investigated the role of potassium channel gene (KCNQ5 polymorphisms in high myopia. We performed a case-control study of 1563 unrelated Han Chinese subjects (809 cases of high myopia and 754 emmetropic controls. Five tag single-nucleotide polymorphisms (SNPs of KCNQ5 were genotyped, and association testing with high myopia was conducted using logistic regression analysis adjusted for sex and age to give Pasym values, and multiple comparisons were corrected by permutation test to give Pemp values. All five noncoding SNPs were associated with high myopia. The SNP rs7744813, previously shown to be associated with refractive error and myopia in two GWAS, showed an odds ratio of 0.75 (95% CI 0.63–0.90; Pemp = 0.0058 for the minor allele. The top SNP rs9342979 showed an odds ratio of 0.75 (95% CI 0.64–0.89; Pemp = 0.0045 for the minor allele. Both SNPs are located within enhancer histone marks and DNase-hypersensitive sites. Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia.

  2. Chronic Periodontitis Genome-wide Association Study in the Hispanic Community Health Study / Study of Latinos.

    Science.gov (United States)

    Sanders, A E; Sofer, T; Wong, Q; Kerr, K F; Agler, C; Shaffer, J R; Beck, J D; Offenbacher, S; Salazar, C R; North, K E; Marazita, M L; Laurie, C C; Singer, R H; Cai, J; Finlayson, T L; Divaris, K

    2017-01-01

    Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large community-based sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P study. There was no replication among the European Americans; however, the TSNAX-DISC1 locus replicated in the African-American sample (rs149133391, minor allele frequency = 0.02, P = 9.1 × 10(-3)), while the 1q22 locus was directionally concordant and nominally significant (rs13373934, P = 4.0 × 10(-2)). This discovery GWAS of interproximal clinical attachment level-a measure of lifetime periodontal tissue destruction-was conducted in a large, community-based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.

  3. Pilot Study of Corneal Sensitivity and Its Association in Keratoconus.

    Science.gov (United States)

    Mandathara, Preeji S; Stapleton, Fiona J; Kokkinakis, Jim; Willcox, Mark D P

    2017-02-01

    To evaluate corneal sensitivity and its association with other clinical parameters in keratoconus. Twenty-four subjects with keratoconus aged between 18 and 65 years were recruited in this cross-sectional study. Ocular symptoms, corneal topography, tear variables such as tear osmolarity, volume and lower tear meniscus height, ocular surface staining, central sensitivity threshold (CST), and corneal subepithelial nerve mapping were obtained. Association between central CST and other clinical variables was examined using the Spearman correlation coefficient. Partial correlation was performed to control for effects of confounding factors. Data from the most severe eye of each subject were included in analyses. Based on the maximum simulated keratometry (Kmax) reading, subjects were graded as having mild (N = 11; K max ≤ 52 D) or severe (N = 13; K max > 52 D) keratoconus. Central corneal sensitivity was lower (ie, increased CST) in the severe keratoconus group compared with that in the mild keratoconus group (median, interquartile range: 1.09; 0.60-19.66 vs. 0.51; 0.39-1.51 g/mm, P = 0.035). In bivariate correlations, reduced corneal sensitivity in keratoconus was associated with age (ρ = 0.42, P = 0.040), disease duration (ρ = 0.49, P = 0.015) and severity (ρ = 0.44; P = 0.032), lower central nerve fiber density (ρ = -0.68, P = 0.014), contact lens wear (ρ = 0.44; P = 0.025), and contact lens tolerance (ρ = 0.46; P = 0.033). After adjusting for contact lens wear, reduced corneal sensitivity was negatively associated with ocular symptoms (ρ = -0.426, P = 0.048) and pain sensitivity (ρ = -0.423, P = 0.045) and positively associated with corneal staining (ρ = 0.52, P = 0.011). Altered corneal sensitivity in keratoconus affected ocular symptoms and ocular surface health, which may have significant impact on the success of management options for keratoconus.

  4. Multiple comparison procedures for neuroimaging genomewide association studies.

    Science.gov (United States)

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

    2015-01-01

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

  5. Feasibility study for banking loan using association rule mining classifier

    Directory of Open Access Journals (Sweden)

    Agus Sasmito Aribowo

    2015-03-01

    Full Text Available The problem of bad loans in the koperasi can be reduced if the koperasi can detect whether member can complete the mortgage debt or decline. The method used for identify characteristic patterns of prospective lenders in this study, called Association Rule Mining Classifier. Pattern of credit member will be converted into knowledge and used to classify other creditors. Classification process would separate creditors into two groups: good credit and bad credit groups. Research using prototyping for implementing the design into an application using programming language and development tool. The process of association rule mining using Weighted Itemset Tidset (WIT–tree methods. The results shown that the method can predict the prospective customer credit. Training data set using 120 customers who already know their credit history. Data test used 61 customers who apply for credit. The results concluded that 42 customers will be paying off their loans and 19 clients are decline

  6. Facial dermatosis associated with Demodex: a case-control study*

    Science.gov (United States)

    Zhao, Ya-e; Peng, Yan; Wang, Xiang-lan; Wu, Li-ping; Wang, Mei; Yan, Hu-ling; Xiao, Sheng-xiang

    2011-01-01

    Demodex has been considered to be related with multiple skin disorders, but controversy persists. In this case-control study, a survey was conducted with 860 dermatosis patients aged 12 to 84 years in Xi’an, China to identify the association between facial dermatosis and Demodex. Amongst the patients, 539 suffered from facial dermatosis and 321 suffered from non-facial dermatosis. Demodex mites were sampled and examined using the skin pressurization method. Multivariate regression analysis was applied to analyze the association between facial dermatosis and Demodex infestation, and to identify the risk factors of Demodex infestation. The results showed that total detection rate of Demodex was 43.0%. Patients aged above 30 years had higher odds of Demodex infestation than those under 30 years. Compared to patients with neutral skin, patients with mixed, oily, or dry skin were more likely to be infested with Demodex (odds ratios (ORs) were 2.5, 2.4, and 1.6, respectively). Moreover, Demodex infestation was found to be statistically associated with rosacea (OR=8.1), steroid-induced dermatitis (OR=2.7), seborrheic dermatitis (OR=2.2), and primary irritation dermatitis (OR=2.1). In particular, ORs calculated from the severe infestation (≥5 mites/cm2) rate were significantly higher than those of the total rate. Therefore, we concluded that Demodex is associated with rosacea, steroid-induced dermatitis, seborrheic dermatitis, and primary irritation dermatitis. The rate of severe infestation is found to be more correlated with various dermatosis than the total infestation rate. The risk factors of Demodex infestation, age, and skin types were identified. Our study also suggested that good hygiene practice might reduce the chances of demodicosis and Demodex infestation. PMID:22135150

  7. Facial dermatosis associated with Demodex: a case-control study.

    Science.gov (United States)

    Zhao, Ya-e; Peng, Yan; Wang, Xiang-lan; Wu, Li-ping; Wang, Mei; Yan, Hu-ling; Xiao, Sheng-xiang

    2011-12-01

    Demodex has been considered to be related with multiple skin disorders, but controversy persists. In this case-control study, a survey was conducted with 860 dermatosis patients aged 12 to 84 years in Xi'an, China to identify the association between facial dermatosis and Demodex. Amongst the patients, 539 suffered from facial dermatosis and 321 suffered from non-facial dermatosis. Demodex mites were sampled and examined using the skin pressurization method. Multivariate regression analysis was applied to analyze the association between facial dermatosis and Demodex infestation, and to identify the risk factors of Demodex infestation. The results showed that total detection rate of Demodex was 43.0%. Patients aged above 30 years had higher odds of Demodex infestation than those under 30 years. Compared to patients with neutral skin, patients with mixed, oily, or dry skin were more likely to be infested with Demodex (odds ratios (ORs) were 2.5, 2.4, and 1.6, respectively). Moreover, Demodex infestation was found to be statistically associated with rosacea (OR=8.1), steroid-induced dermatitis (OR=2.7), seborrheic dermatitis (OR=2.2), and primary irritation dermatitis (OR=2.1). In particular, ORs calculated from the severe infestation (≥5 mites/cm(2)) rate were significantly higher than those of the total rate. Therefore, we concluded that Demodex is associated with rosacea, steroid-induced dermatitis, seborrheic dermatitis, and primary irritation dermatitis. The rate of severe infestation is found to be more correlated with various dermatosis than the total infestation rate. The risk factors of Demodex infestation, age, and skin types were identified. Our study also suggested that good hygiene practice might reduce the chances of demodicosis and Demodex infestation.

  8. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; van Duijn, Cornelia M; Ugocsai, Peter

    2012-01-01

    , and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57...... phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204)) and 10 loci for sphingolipids...

  9. 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.

  10. Progress of genome wide association study in domestic animals.

    Science.gov (United States)

    Zhang, Hui; Wang, Zhipeng; Wang, Shouzhi; Li, Hui

    2012-08-22

    Domestic animals are invaluable resources for study of the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) responsible for economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured because of the low density of markers used in QTL mapping studies. The genome wide association study (GWAS), which utilizes high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Encouraging achievements in dissection of the genetic mechanisms of complex diseases in humans have resulted from the use of GWAS. At present, GWAS has been applied to the field of domestic animal breeding and genetics, and some advances have been made. Many genes or markers that affect economic traits of interest in domestic animals have been identified. In this review, advances in the use of GWAS in domestic animals are described.

  11. Considerations for Pharmacoepidemiological Studies of Drug-Cancer Associations

    DEFF Research Database (Denmark)

    Pottegård, Anton; Friis, Søren; Stürmer, Til

    2018-01-01

    and future perspectives. Aspects of data sources include assessment of complete history of drug use and data on dose and duration of drug use, allowing estimates of cumulative exposure. Outcome data from formal cancer registries are preferable, but cancer data from other sources, for example, patient......In this MiniReview, we provide general considerations for the planning and conduct of pharmacoepidemiological studies of associations between drug use and cancer development. We address data sources, study design, assessment of drug exposure, ascertainment of cancer outcomes, confounder adjustment...... period of cancer development. We present methods to examine early and late effects of drug use on cancer development and discuss the need for employing 'lag-time' in order to avoid reverse causation. We emphasize that a new-user study design should always be considered. We also underline the need...

  12. Association between kyphosis and subacromial impingement syndrome: LOHAS study.

    Science.gov (United States)

    Otoshi, Kenichi; Takegami, Misa; Sekiguchi, Miho; Onishi, Yoshihiro; Yamazaki, Shin; Otani, Koji; Shishido, Hiroaki; Kikuchi, Shinichi; Konno, Shinichi

    2014-12-01

    Kyphosis is a cause of scapular dyskinesis, which can induce various shoulder disorders, including subacromial impingement syndrome (SIS). This study aimed to clarify the impact of kyphosis on SIS with use of cross-sectional data from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS). The study enrolled 2144 participants who were older than 40 years and participated in health checkups in 2010. Kyphosis was assessed by the wall-occiput test (WOT) for thoracic kyphosis and the rib-pelvic distance test (RPDT) for lumbar kyphosis. The associations between kyphosis, SIS, and reduction in shoulder elevation (RSE) were investigated. Age- and gender-adjusted logistic regression analysis demonstrated significant association between SIS and WOT (odds ratio, 1.65; 95% confidence interval, 1.02, 2.64; P shoulder elevation induced by the restriction of the thoracic spine extension and scapular dyskinesis. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  13. Detecting rare variants in case-parents association studies.

    Directory of Open Access Journals (Sweden)

    Kuang-Fu Cheng

    Full Text Available Despite the success of genome-wide association studies (GWASs in detecting common variants (minor allele frequency ≥0.05 many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT, multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

  14. [Statin associated myopathy in clinical practice. Results of DAMA study].

    Science.gov (United States)

    Millán, Jesús; Pedro-Botet, Juan; Climent, Elisenda; Millán, Joaquín; Rius, Joan

    Muscle symptoms, with or without elevation of creatin kinase are one of the main adverse effects of statin therapy, a fact that sometimes limits their use. The aim of this study was to evaluate the clinical characteristics of patients treated with statins who have complained muscle symptoms and to identify possible predictive factors. A cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. 3,845 patients were recruited from a one-day record from 2,001 physicians. Myalgia was present in 78.2% of patients included in the study, myositis in 19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d in women) and abdominal obesity were the clinical situations associated with statin myopathy. Myalgia followed by myositis are the most frequent statin-related side effects. It should be recommended control environmental factors such as intense exercise and alcohol intake as well as abdominal obesity and renal function of the patient treated with statins. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Capillary Rarefaction Associates with Albuminuria: The Maastricht Study.

    Science.gov (United States)

    Martens, Remy J H; Henry, Ronald M A; Houben, Alfons J H M; van der Kallen, Carla J H; Kroon, Abraham A; Schalkwijk, Casper G; Schram, Miranda T; Sep, Simone J S; Schaper, Nicolaas C; Dagnelie, Pieter C; Muris, Dennis M J; Gronenschild, Ed H B M; van der Sande, Frank M; Leunissen, Karel M L; Kooman, Jeroen P; Stehouwer, Coen D A

    2016-12-01

    Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria. Copyright © 2016 by the American Society of Nephrology.

  16. [Risk factors associated with preeclampsia: case-control study].

    Science.gov (United States)

    Morgan-Ortiz, Fred; Calderón-Lara, Sergio Alberto; Martínez-Félix, Jesús Israel; González-Beltrán, Aurelio; Quevedo-Castro, Everardo

    2010-03-01

    Preeclampsia is one of the most frequent and serious complication of pregnancy characterized by systemic perfusion reduction generated by vasospasm and activation of coagulation systems. To evaluate the association between preeclampsia sociodemographics and obstetrics antecedents. An unmatched case-control study was carried out in which all the clinical registries of patients with preeclampsia (cases: n = 196) assisted in the period 2003-2007 in the Hospital Civil of Culiacan, Sinaloa State of Mexico were analyzed. As controls the clinical registries of patients assisted during the same period were selected at random but that they didn't show up preeclampsia (n = 470). The association of preeclampsia with socioeconomic level, tobacco use, alcohol use, gynecologic and obstetric antecedents (sexual partners, pregnancies, deliveries and abortions number, prenatal control, contraceptive method) and previous pregnancy with preeclampsia were analyzed. There were not association between tobacco use (OR: 3.05; 95% CI: 0.81-11.48), beginning of sexual activity (p = 0.1509), number of sexual partners (OR: 1.23; 95% CI: 0.83-1.83; p = 0.3009) and sexual cohabitation less than 12 months (OR: 0.90; 95% CI: 0.63-1.27). The alcoholism (OR: 5.77; 95% CI: 1.48-22.53), socioeconomic level (p alcoholism, low socioeconomic level and pregnancy previous with preeclampsia.

  17. Association between diabetes and tuberculosis: case-control study

    Directory of Open Access Journals (Sweden)

    Susan Martins Pereira

    Full Text Available ABSTRACT OBJECTIVE To test the association between diabetes and tuberculosis. METHODS It is a case-control study, matched by age and sex. We included 323 new cases of tuberculosis with positive results for bacilloscopy. The controls were 323 respiratory symptomatic patients with negative bacilloscopy, from the same health services, such as: ambulatory cases from three referral hospitals and six basic health units responsible for the notifications of new cases of tuberculosis in Salvador, Bahia. Data collection occurred between 2008 and 2010. The instruments used were structured interview, including clinical data, capillary blood glucose (during fasting or postprandial, and the CAGE questionnaire for screening of abusive consumption of alcohol. Descriptive, exploratory, and multivariate analysis was performed using conditional logistic regression. RESULTS The average age of the cases was 38.5 (SD = 14.2 years and of the controls, 38.5 (SD = 14.3 years. Among cases and controls, most subjects (61% were male. In univariate analysis we found association between the occurrence of diabetes and tuberculosis (OR = 2.37; 95%CI 1.04–5.42, which remained statistically significant after adjustment for potential confounders (OR = 3.12; 95%CI 1.12–7.94. CONCLUSIONS The association between diabetes and tuberculosis can hinder the control of tuberculosis, contributing to the maintainance of the disease burden. The situation demands increasing early detection of diabetes among people with tuberculosis, in an attempt to improve disease control strategies.

  18. Association between trochlear morphology and chondromalacia patella: an MRI study.

    Science.gov (United States)

    Duran, Semra; Cavusoglu, Mehtap; Kocadal, Onur; Sakman, Bulent

    This study aimed to compare trochlear morphology seen in magnetic resonance imaging between patients with chondromalacia patella and age-matched control patients without cartilage lesion. Trochlear morphology was evaluated using the lateral trochlear inclination, medial trochlear inclination, sulcus angle and trochlear angle on the axial magnetic resonance images. Consequently, an association between abnormal trochlear morphology and chondromalacia patella was identified in women. In particular, women with flattened lateral trochlea are at an increased risk of patellar cartilage structural damage. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

    Science.gov (United States)

    Yuan, Jingwei; Sun, Congjiao; Dou, Taocun; Yi, Guoqiang; Qu, LuJiang; Qu, Liang; Wang, Kehua; Yang, Ning

    2015-01-01

    Egg number (EN), egg laying rate (LR) and age at first egg (AFE) are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS) was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens.

  20. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

    Directory of Open Access Journals (Sweden)

    Jingwei Yuan

    Full Text Available Egg number (EN, egg laying rate (LR and age at first egg (AFE are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens.

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

    Science.gov (United States)

    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; Leach, I. Mateo; 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.

    2016-01-01

    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 meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10–7) and 13% for RAB38/CTSC (P = 5.8 × 10−7). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PMID:26631737

  2. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study.

    Science.gov (United States)

    Moss, Davina J Hensman; Pardiñas, Antonio F; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J

    2017-09-01

    Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003-13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10(-10)) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10(-8)DHFR p=8·37 × 10(-7) MTRNR2L2 p=2·15 × 10(-9)) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10(-4)DHFR p=8·45 × 10(-4)MTRNR2L2 p=1·20 × 10(-3)). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome

  3. [Immigration and factors associated with breastfeeding. CALINA study].

    Science.gov (United States)

    Oves Suárez, B; Escartín Madurga, L; Samper Villagrasa, M P; Cuadrón Andrés, L; Alvarez Sauras, M L; Lasarte Velillas, J J; Moreno Aznar, L A; Rodríguez Martínez, G

    2014-07-01

    To identify socio-cultural, obstetric and perinatal characteristics associated with complete breastfeeding (CBF) during the first 4 months of age, depending on maternal origin. Socio-cultural, obstetric and perinatal aspects associated with breastfeeding depending on maternal origin were evaluated in a longitudinal study in a representative infant population from Aragon (n = 1452). The prevalence of CBF was higher in immigrant mothers than in those from Spain. CBF was maintained in 37.2% of mothers from Spain at 4 months, compared with 43% of immigrants (P=.039) (RR Spanish/immigrants=0.76; 95% CI: 0.58-0.99); at 6 months this occurred in 13.9% vs. 23.8%, respectively (Pimmigrants=0.52; 95% CI: 0.37-0.72). The factors associated with CBF at 4 months are different between both groups. Mothers born in Spain are older (P=.002), have higher academic level (P=.001), greater parity (P=.003), and a higher probability of vaginal delivery (P=.005); and their children have the highest anthropometric values at birth. However, in immigrant mothers, the maintenance of CBF was associated with a higher maternal body mass index and with working at home. In both groups, CBF remains more frequently in those mothers who do not smoke (P=.001). The prevalence of CBF during the first months of life is higher in immigrant mothers than in those from Spain, and socio-cultural, obstetric and perinatal factors are different, depending on maternal origin. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Dental trauma in association with maxillofacial fractures: an epidemiological study.

    Science.gov (United States)

    Ruslin, Muhammad; Wolff, Jan; Boffano, Paolo; Brand, Henk S; Forouzanfar, Tymour

    2015-08-01

    The aim of this study was to retrospectively investigate the incidence and associated factors of dental trauma in patients with maxillofacial fractures at the VU Medical Center in Amsterdam. Data from 707 patients who were treated surgically for maxillofacial fractures were evaluated. The data were collected retrospectively from patient files and other available databases. The data collected included date of fracture, age, gender, type of fracture, and injured teeth. Of the total 707 patients, 164 patients (23.2%) presented dental injuries associated with facial fractures. Mandibular condylar fractures, mandibular parasymphyseal fractures, Le Fort fractures, and mandibular body fractures were found to be significantly more associated with dental injury. Zygomatic arch or zygomatic complex fractures were significantly less associated with dental injury. Women had a significant higher risk of facial fractures with dental injuries than men. The maxilla demonstrated the highest incidence of injured teeth. The most affected teeth were the maxillary incisors (33.1%), followed by mandible incisors (13.6%), mandible molars (12.8%), and maxillary premolars (12.6%). Our findings show a higher risk of dental injury among patients with a mandibular condylar fracture and mandibular parasymphyseal fracture but a lower risk of dental injury among patients with a zygomatic arch or zygomatic complex fracture. On average, patients had more than three injured teeth, with most of the injured teeth being in the upper jaw. The maxillary incisors, followed by the mandible incisors, were the most injured teeth. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Association between androgenetic alopecia and hyperlipidemia: a comparative study

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    Ramin Taheri

    2013-12-01

    Full Text Available Background: Androgenetic alopecia (AGA is the most common type of progressive balding that appears with early loss of hair, chiefly from the vertex. There has been significant relationship between AGA with coronary artery disease and related risk factors, such as hypertension in some studies. The aim of this study is to investigate the association between androgenetic alopecia with hyperlipidemia.Methods: This cross-sectional study was performed on 112 patients with vertex type AGA (in male grade 3 or higher Hamilton- Norwood scale, and in female grade 2 or higher Ludwig scale (study group and 115 persons age and sex matched, with normal hair status (Normal group. None of participants had diabetes mellitus, hypothyroidism, liver disease, kidney disease and none of them had history of smoking and using drugs with effect on serum lipids. They were 20-35 years old and their body mass index were 20-30. Blood samples were obtained following 12 hours fasting status and serum levels of triglyceride (TG, cholesterol, high-density lipoprotein (HDL and low-density lipoprotein (LDL were determined using standard laboratory methods. Total cholesterol greater than 240 or TG greater than 200 or LDL greater than 160 or HDL less than 40 in men or HDL less than 50 in women were considered hyperlipidemia.Results: In androgenetic alopecia group 46.4% and 47% of normal group were female. Mean (±SE of total cholesterol (172.4±3.1, 148.8±3.1, P 0.05.Conclusion: The findings showed that there is no relationship between AGA and hyperlipidemia. Regarding to high levels of total cholesterol, LDL and triglyceride in AGA patients, it seems that, AGA increases risk of coronary heart disease. To determine a definite association between AGA and hyperlipidemia more studies are recommended.

  6. A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Simon Baron-Cohen

    Full Text Available Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419 versus low (n = 183 mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10(-5, 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10(-6. In this analysis, one of the SNPs (rs789859 showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115 were nominally significant (lowest p-value 3.278 × 10(-4. Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64. The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study.

  7. A genome wide association study of mathematical ability reveals an association at chromosome 3q29, a locus associated with autism and learning difficulties: a preliminary study.

    Science.gov (United States)

    Baron-Cohen, Simon; Murphy, Laura; Chakrabarti, Bhismadev; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Warrier, Varun

    2014-01-01

    Mathematical ability is heritable, but few studies have directly investigated its molecular genetic basis. Here we aimed to identify specific genetic contributions to variation in mathematical ability. We carried out a genome wide association scan using pooled DNA in two groups of U.K. samples, based on end of secondary/high school national academic exam achievement: high (n = 419) versus low (n = 183) mathematical ability while controlling for their verbal ability. Significant differences in allele frequencies between these groups were searched for in 906,600 SNPs using the Affymetrix GeneChip Human Mapping version 6.0 array. After meeting a threshold of p<1.5×10(-5), 12 SNPs from the pooled association analysis were individually genotyped in 542 of the participants and analyzed to validate the initial associations (lowest p-value 1.14 ×10(-6)). In this analysis, one of the SNPs (rs789859) showed significant association after Bonferroni correction, and four (rs10873824, rs4144887, rs12130910 rs2809115) were nominally significant (lowest p-value 3.278 × 10(-4)). Three of the SNPs of interest are located within, or near to, known genes (FAM43A, SFT2D1, C14orf64). The SNP that showed the strongest association, rs789859, is located in a region on chromosome 3q29 that has been previously linked to learning difficulties and autism. rs789859 lies 1.3 kbp downstream of LSG1, and 700 bp upstream of FAM43A, mapping within the potential promoter/regulatory region of the latter. To our knowledge, this is only the second study to investigate the association of genetic variants with mathematical ability, and it highlights a number of interesting markers for future study.

  8. Factors Associated With Pharmacy Student Interest in International Study

    Science.gov (United States)

    Owen, Chelsea; Breheny, Patrick; Ingram, Richard; Pfeifle, William; Cain, Jeff

    2013-01-01

    Objectives. To examine the interest of pharmacy students in international study, the demographic factors and involvement characteristics associated with that interest, and the perceived advantages and barriers of engaging in international opportunities during pharmacy school. Methods. A self-administered electronic survey instrument was distributed to first-, second-, and third-year pharmacy students at the University of Kentucky College of Pharmacy. Results. There were 192 total respondents, for a response rate of 50.9%. Seventy-two percent reported interest in international study. Previous international study experience (p=0.001), previous international travel experience (p=0.002), year in pharmacy school (p=0.03), level of academic involvement (pstudy interest. Positive influences to international study included desire to travel and availability of scholarships. Perceived barriers included an inability to pay expenses and lack of foreign language knowledge. Conclusions. The needs and interests of pharmacy students should be considered in the development and expansion of internationalization programs in order to effectively optimize global partnerships and available international experiences. Colleges and schools of pharmacy should engage students early in the curriculum when interest in study-abroad opportunities is highest and seek to alleviate concerns about expenses as a primary influence on study-abroad decisions through provision of financial assistance. PMID:23610472

  9. GPFrontend and GPGraphics: graphical analysis tools for genetic association studies

    Directory of Open Access Journals (Sweden)

    Schanze Denny

    2010-09-01

    Full Text Available Abstract Background Most software packages for whole genome association studies are non-graphical, purely text based programs originally designed to run with UNIX-like operating systems. Graphical output is often not intended or supposed to be performed with other command line tools, e.g. gnuplot. Results Using the Microsoft .NET 2.0 platform and Visual Studio 2005, we have created a graphical software package to analyze data from microarray whole genome association studies, both for a DNA-pooling based approach as well as regular single sample data. Part of this package was made to integrate with GenePool 0.8.2, a previously existing software suite for GNU/Linux systems, which we have modified to run in a Microsoft Windows environment. Further modifications cause it to generate some additional data. This enables GenePool to interact with the .NET parts created by us. The programs we developed are GPFrontend, a graphical user interface and frontend to use GenePool and create metadata files for it, and GPGraphics, a program to further analyze and graphically evaluate output of different WGA analysis programs, among them also GenePool. Conclusions Our programs enable regular MS Windows users without much experience in bioinformatics to easily visualize whole genome data from a variety of sources.

  10. Association between protein intake and blood pressure: the INTERMAP Study.

    Science.gov (United States)

    Elliott, Paul; Stamler, Jeremiah; Dyer, Alan R; Appel, Lawrence; Dennis, Barbara; Kesteloot, Hugo; Ueshima, Hirotsugu; Okayama, Akira; Chan, Queenie; Garside, Daniel B; Zhou, Beifan

    2006-01-09

    Findings from epidemiological studies suggest an inverse relationship between individuals' protein intake and their blood pressure. Cross-sectional epidemiological study of 4680 persons, aged 40 to 59 years, from 4 countries. Systolic and diastolic blood pressure was measured 8 times at 4 visits. Dietary intake based on 24-hour dietary recalls was recorded 4 times. Information on dietary supplements was noted. Two 24-hour urine samples were obtained per person. There was a significant inverse relationship between vegetable protein intake and blood pressure. After adjusting for confounders, blood pressure differences associated with higher vegetable protein intake of 2.8% kilocalories were -2.14 mm Hg systolic and -1.35 mm Hg diastolic (Pweight, these differences were -1.11 mm Hg systolic (Pprotein intake, significant positive blood pressure differences did not persist after adjusting for height and weight. For total protein intake (which had a significant interaction with sex), there was no significant association with blood pressure in women, nor in men after adjusting for dietary confounders. There were significant differences in the amino acid content of the diets of persons with high vegetable and low animal protein intake vs the diets of persons with low vegetable and high animal protein intake. Vegetable protein intake was inversely related to blood pressure. This finding is consistent with recommendations that a diet high in vegetable products be part of healthy lifestyle for prevention of high blood pressure and related diseases.

  11. An evolutionary framework for association testing in resequencing studies.

    Directory of Open Access Journals (Sweden)

    C Ryan King

    2010-11-01

    Full Text Available Sequencing technologies are becoming cheap enough to apply to large numbers of study participants and promise to provide new insights into human phenotypes by bringing to light rare and previously unknown genetic variants. We develop a new framework for the analysis of sequence data that incorporates all of the major features of previously proposed approaches, including those focused on allele counts and allele burden, but is both more general and more powerful. We harness population genetic theory to provide prior information on effect sizes and to create a pooling strategy for information from rare variants. Our method, EMMPAT (Evolutionary Mixed Model for Pooled Association Testing, generates a single test per gene (substantially reducing multiple testing concerns, facilitates graphical summaries, and improves the interpretation of results by allowing calculation of attributable variance. Simulations show that, relative to previously used approaches, our method increases the power to detect genes that affect phenotype when natural selection has kept alleles with large effect sizes rare. We demonstrate our approach on a population-based re-sequencing study of association between serum triglycerides and variation in ANGPTL4.

  12. AWS certified solutions architect official study guide associate exam

    CERN Document Server

    Baron, Joe; Bixler, Tim; Gaut, Biff; Kelly, Kevin E; Senior, Sean; Stamper, John

    2017-01-01

    This is your opportunity to take the next step in your career by expanding and validating your skills on the AWS cloud. AWS has been the frontrunner in cloud computing products and services, and the AWS Certified Solutions Architect Official Study Guide for the Associate exam will get you fully prepared through expert content, and real-world knowledge, key exam essentials, chapter review questions, access to Sybex's interactive online learning environment, and much more. This official study guide, written by AWS experts, covers exam concepts, and provides key review on exam topics, including: * Mapping Multi-Tier Architectures to AWS Services, such as web/app servers, firewalls, caches and load balancers * Understanding managed RDBMS through AWS RDS (MySQL, Oracle, SQL Server, Postgres, Aurora) * Understanding Loose Coupling and Stateless Systems * Comparing Different Consistency Models in AWS Services * Understanding how AWS CloudFront can make your application more cost efficient, faster and secure * Implem...

  13. Family Stigma Associated With Epilepsy: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Reza nabi amjad

    2017-03-01

    Full Text Available Introduction: Harmful nature of epilepsy can affect the patient and their parent. Stigma, arising from it, affects the patient and their family. To relieve it understanding the experiences of the parent are useful. This study was aimed at understanding the experiences of parent of child with epilepsy in Iran. Methods: In this interpretative phenomenological study, 10 parents who took care of their child with epilepsy were participated. Data were collected through in-depth semi-structured interviews. After transcription, data were analyzed using Van Manen’s method. Results: Family stigma emerged as a main theme in data analysis with three subthemes including becoming verbally abusive, a dull and heavy shadowed look, and associates interference. Conclusion: Family stigma is a major challenge for parents of child with epilepsy need to special attention by health system. Nurses, as a big part of the system, can play an important role to manage this problem.

  14. [Myelopathy associated with HTLV-1: clinical electrophysiologic study].

    Science.gov (United States)

    Matsumoto, S C; Nakasato, O; Kataoka, A; Inayoshi, S; Okajima, T

    1993-11-01

    Clinical and electrophysiological studies have been performed in 9 cases of HTLV-I associated myelopathy (7 female, 2 male). Spastic paraparesis and neurogenic bladder were present in 8; sensory disturbances were detected only in 4. The conduction velocities of the posterior tibial and sural nerves were reduced in 2 cases. Median nerve SSEP revealed a delay of N11, N13, N14, N20 peak latencies and an increase of N9-N20, N13-N14 and N13-N20 interpeak latencies. The electrophysiological studies are the most accurate indicators of the diffuse involvement not only of central motor and sensory pathways but also of the peripheral nervous system.

  15. Validation of genome-wide association studies (GWAS) results.

    Science.gov (United States)

    Henshall, John M

    2013-01-01

    Validation of the results of genome-wide association studies or genomic selection studies is an essential component of the experimental program. Validation allows users to quantify the benefit of applying gene tests or genomic prediction, relative to the costs of implementing the program. Further, if implemented, an appropriate weight in a selection index can only be derived if estimates of the accuracy of genomic predictions are available. In this chapter the reasons for validation are explored, and a range of commonly encountered scenarios described. General principles are stated, and options for performing validation discussed. Designs for validation are heavily dependent on the availability of phenotyped animals, and also on the pedigree structures that characterize the breeding program. Consequently, there is no single plan that is always applicable, and a custom plan often must be developed.

  16. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    DEFF Research Database (Denmark)

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur

    2014-01-01

    Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.......Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects....

  17. Association between day of delivery and obstetric outcomes: observational study.

    Science.gov (United States)

    Palmer, William L; Bottle, A; Aylin, P

    2015-11-24

    What is the association between day of delivery and measures of quality and safety of maternity services, particularly comparing weekend with weekday performance? This observational study examined outcomes for maternal and neonatal records (1,332,835 deliveries and 1,349,599 births between 1 April 2010 and 31 March 2012) within the nationwide administrative dataset for English National Health Service hospitals by day of the week. Groups were defined by day of admission (for maternal indicators) or delivery (for neonatal indicators) rather than by day of complication. Logistic regression was used to adjust for case mix factors including gestational age, birth weight, and maternal age. Staffing factors were also investigated using multilevel models to evaluate the association between outcomes and level of consultant presence. The primary outcomes were perinatal mortality and-for both neonate and mother-infections, emergency readmissions, and injuries. Performance across four of the seven measures was significantly worse for women admitted, and babies born, at weekends. In particular, the perinatal mortality rate was 7.3 per 1000 babies delivered at weekends, 0.9 per 1000 higher than for weekdays (adjusted odds ratio 1.07, 95% confidence interval 1.02 to 1.13). No consistent association between outcomes and staffing was identified, although trusts that complied with recommended levels of consultant presence had a perineal tear rate of 3.0% compared with 3.3% for non-compliant services (adjusted odds ratio 1.21, 1.00 to 1.45). Limitations of the analysis include the method of categorising performance temporally, which was mitigated by using a midweek reference day (Tuesday). Further research is needed to investigate possible bias from unmeasured confounders and explore the nature of the causal relationship. This study provides an evaluation of the "weekend effect" in obstetric care, covering a range of outcomes. The results would suggest approximately 770 perinatal

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

    Science.gov (United States)

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

    2010-01-01

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

  19. Comorbidities Associated with Obstructive Sleep Apnea: a Retrospective Study

    Science.gov (United States)

    Pinto, José Antonio; Ribeiro, Davi Knoll; Cavallini, Andre Freitas da Silva; Duarte, Caue; Freitas, Gabriel Santos

    2016-01-01

    Introduction Obstructive sleep apnea (OSA) is characterized by partial or complete recurrent upper airway obstruction during sleep. OSA brings many adverse consequences, such as hypertension, obesity, diabetes mellitus, cardiac and encephalic alterations, behavioral, among others, resulting in a significant source of public health care by generating a high financial and social impact. The importance of this assessment proves to be useful, because the incidence of patients with comorbidities associated with AOS has been increasing consistently and presents significant influence in natural disease history. Objective The objective of this study is to assess major comorbidities associated with obstructive sleep apnea (OSA) and prevalence in a group of patients diagnosed clinically and polysomnographically with OSA. Methods This is a retrospective study of 100 charts from patients previously diagnosed with OSA in our service between October 2010 and January 2013. Results We evaluated 100 patients with OSA (84 men and 16 women) with a mean age of 50.05 years (range 19–75 years). The prevalence of comorbidities were hypertension (39%), obesity (34%), depression (19%), gastroesophageal reflux disease (GERD) (18%), diabetes mellitus (15%), hypercholesterolemia (10%), asthma (4%), and no comorbidities (33%). Comorbidities occurred in 56.2% patients diagnosed with mild OSA, 67.6% with moderate OSA, and 70% of patients with severe OSA. Conclusion According to the current literature data and the values obtained in our paper, we can correlate through expressive values obesity with OSA and their apnea hypopnea index (AHI) values. However, despite significant prevalence of OSA with other comorbidities, our study could not render expressive significance values able to justify their correlations. PMID:27096019

  20. Associations of childhood eczema severity: A US population based study

    Science.gov (United States)

    Silverberg, Jonathan I.; Simpson, Eric L.

    2014-01-01

    Little is known about predictors of eczema severity in the US population. We sought to determine the distribution and associations of childhood eczema severity in the US. We analyzed data from the 2007 National Survey of Children's Health, a prospective questionnaire-based study of a nationally representative sample of 91,642 children (0-17yr). The prevalence of childhood eczema was 12.97% (95% confidence interval [95% CI]=12.42–13.53); 67.0% (95% CI: 64.8–69.2) had mild, 26.0% (95% CI: 23.9–28.1) moderate and 7.0% (95% CI: 5.8–8.3) severe disease. There was significant statewide-variation of the distribution of eczema severity (Rao-Scott chi square, P=0.004), with highest rates of severe disease in Northeastern and Midwestern states. In univariate models, eczema severity was increased with older age, African-American and Hispanic race/ethnicity, lower household income, oldest child in the family, home with a single mother, lower paternal/maternal education level, maternal general health, maternal/paternal emotional health, dilapidated housing and garbage on the streets. In multivariate survey logistic regression models using stepwise and backward selection, moderate–severe eczema was associated with older age, lower household income and fair or poor maternal health, but inversely associated with birthplace outside the US. These data indicate that environmental and/or lifestyle factors play an important role in eczema severity. PMID:24819283

  1. A prospective study of associations among helping, health, and longevity.

    Science.gov (United States)

    Hilbrand, Sonja; Coall, David A; Meyer, Andrea H; Gerstorf, Denis; Hertwig, Ralph

    2017-08-01

    How does helping behavior contribute to the health and the longevity of older helpers? From an evolutionary perspective, the ultimate cause may be rooted in ancestral parenting and grandparenting. These activities may have generalized to a neural and hormonal caregiving system that also enabled prosocial behavior beyond the family. From a psychological perspective, helping others may be associated with healthy aging, which, in turn, contributes to longevity as a proximate cause. Yet little is known about the extent to which mediating factors such as the health benefits of helping behaviors translate into enhanced longevity, particularly in regard to grandparenting. To fill this gap, we conducted mediation analyses (structural equation models) to examine whether grandparenting and supporting others in the social network contributed directly or indirectly (through better health 5-6 years later) to the longevity of older helpers. We drew on longitudinal data from the Berlin Aging Study (N = 516), in which older adults in Berlin, Germany, were interviewed at baseline (1990-1993, mean age at entry = 85 years) and continuously followed up until 2009. Results suggest that the associations of both grandparenting and supporting others with enhanced longevity are mediated by better prospective health (indirect effect). The effect of helping was not fully mediated, however-helping was also directly associated with increased longevity independently of the health indicators measured. The results were robust against effects of the helper's preexisting health status and sociodemographic characteristics of participants, their children, and grandchildren. We conclude that better prospective health contributes to the link between helping and longevity, but does not fully account for it. Other potential contributing mechanisms remain to be identified. As populations age across the globe, identifying mechanisms that foster health in old age can help to highlight potential targets

  2. Association studies in late onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Goate, A.M.; Lendon, C.; Talbot, C. [Washington Univ. School of Medicine, St. Louis, MO (United States)] [and others

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  3. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  4. Association study of AMH and AMHRII polymorphisms with unexplained infertility.

    Science.gov (United States)

    Rigon, Chiara; Andrisani, Alessandra; Forzan, Monica; D'Antona, Donato; Bruson, Alice; Cosmi, Erich; Ambrosini, Guido; Tiboni, Gian Mario; Clementi, Maurizio

    2010-09-01

    To investigate the association of AMH and AMHRII polymorphisms with reproductive abilities in a sample of women with idiopathic infertility. Case-control study. University Department of Obstetrics and Gynecology, and University Unit of Clinical Genetics. 76 women with idiopathic sterility and 100 fertile women as controls. Genotyping was performed by high-resolution melt analysis. Genotype distribution and allele frequency of AMH and AMHRII polymorphisms. Reconstruction of haplotype alleles to evaluate the linkage disequilibrium between single nucleotide polymorphisms. Allele frequencies of -482 A>G, IVS 5-6 C>T, IVS 10+77 A>G, 146T>G polymorphisms are statistically significantly different in infertile patients compared with controls. Genetic variants of AMH and AMHRII genes seem to be associated with infertility, suggesting a role in the pathophysiology of normo-estrogenic and normo-ovulatory infertility. A clearer understanding of their function in ovarian physiology may help clinicians to find a role for antimüllerian hormone measurement in the field of reproductive medicine. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. 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)).

  6. Semantically enabling a genome-wide association study database

    Directory of Open Access Journals (Sweden)

    Beck Tim

    2012-12-01

    Full Text Available Abstract Background The amount of data generated from genome-wide association studies (GWAS has grown rapidly, but considerations for GWAS phenotype data reuse and interchange have not kept pace. This impacts on the work of GWAS Central – a free and open access resource for the advanced querying and comparison of summary-level genetic association data. The benefits of employing ontologies for standardising and structuring data are widely accepted. The complex spectrum of observed human phenotypes (and traits, and the requirement for cross-species phenotype comparisons, calls for reflection on the most appropriate solution for the organisation of human phenotype data. The Semantic Web provides standards for the possibility of further integration of GWAS data and the ability to contribute to the web of Linked Data. Results A pragmatic consideration when applying phenotype ontologies to GWAS data is the ability to retrieve all data, at the most granular level possible, from querying a single ontology graph. We found the Medical Subject Headings (MeSH terminology suitable for describing all traits (diseases and medical signs and symptoms at various levels of granularity and the Human Phenotype Ontology (HPO most suitable for describing phenotypic abnormalities (medical signs and symptoms at the most granular level. Diseases within MeSH are mapped to HPO to infer the phenotypic abnormalities associated with diseases. Building on the rich semantic phenotype annotation layer, we are able to make cross-species phenotype comparisons and publish a core subset of GWAS data as RDF nanopublications. Conclusions We present a methodology for applying phenotype annotations to a comprehensive genome-wide association dataset and for ensuring compatibility with the Semantic Web. The annotations are used to assist with cross-species genotype and phenotype comparisons. However, further processing and deconstructions of terms may be required to facilitate automatic

  7. Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells With DNA Methylation Changes in Epithelial Cancer.

    Science.gov (United States)

    Teschendorff, Andrew E; Yang, Zhen; Wong, Andrew; Pipinikas, Christodoulos P; Jiao, Yinming; Jones, Allison; Anjum, Shahzia; Hardy, Rebecca; Salvesen, Helga B; Thirlwell, Christina; Janes, Samuel M; Kuh, Diana; Widschwendter, Martin

    2015-07-01

    The utility of buccal cells as an epithelial source tissue for epigenome-wide association studies (EWASs) remains to be demonstrated. Given the direct exposure of buccal cells to potent carcinogens such as smoke, epigenetic changes in these cells may provide insights into the development of smoke-related cancers. To perform an EWAS in buccal and blood cells to assess the relative effect of smoking on the DNA methylation (DNAme) patterns in these cell types and to test whether these DNAme changes are also seen in epithelial cancer. In 2013, we measured DNAme at more than 480,000 CpG sites in buccal samples provided in 1999 by 790 women (all aged 53 years in 1999) from the United Kingdom Medical Research Council National Survey of Health and Development. This included matched blood samples from 152 women. We constructed a DNAme-based smoking index and tested its sensitivity and specificity to discriminate normal from cancer tissue in more than 5000 samples. CpG sites whose DNAme level correlates with smoking pack-years, and construction of an associated sample-specific smoking index, which measures the mean deviation of DNAme at smoking-associated CpG sites from a normal reference. In a discovery set of 400 women, we identified 1501 smoking-associated CpG sites at a genome-wide significance level of P smoking index constructed from the DNAme changes in buccal cells was able to discriminate normal tissue from cancer tissue with a mean receiver operating characteristic area under the curve of 0.99 (range, 0.99-1.00) for lung cancers and of 0.91 (range, 0.71-1.00) for 13 other organs. The corresponding area under the curve of a smoking signature derived from blood cells was lower than that derived from buccal cells in 14 of 15 cancer types (Wilcoxon signed rank test, P = .001). These data point toward buccal cells as being a more appropriate source of tissue than blood to conduct EWASs for smoking-related epithelial cancers.

  8. The advent of genome-wide association studies for bacteria.

    Science.gov (United States)

    Chen, Peter E; Shapiro, B Jesse

    2015-06-01

    Significant advances in sequencing technologies and genome-wide association studies (GWAS) have revealed substantial insight into the genetic architecture of human phenotypes. In recent years, the application of this approach in bacteria has begun to reveal the genetic basis of bacterial host preference, antibiotic resistance, and virulence. Here, we consider relevant differences between bacterial and human genome dynamics, apply GWAS to a global sample of Mycobacterium tuberculosis genomes to highlight the impacts of linkage disequilibrium, population stratification, and natural selection, and finally compare the traditional GWAS against phyC, a contrasting method of mapping genotype to phenotype based upon evolutionary convergence. We discuss strengths and weaknesses of both methods, and make suggestions for factors to be considered in future bacterial GWAS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Community-Associated Methicillin-Resistant Staphylococcus aureus Case Studies

    Science.gov (United States)

    Sowash, Madeleine G.; Uhlemann, Anne-Catrin

    2014-01-01

    Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highlight a wide range of the clinical presentations and challenges of CA-MRSA. Based on these cases we further explore the globally polygenetic background of CA-MRSA with a special emphasis on generally less characterized populations. PMID:24085688

  10. A genome-wide association study of pulmonary function measures in the Framingham Heart Study.

    Directory of Open Access Journals (Sweden)

    Jemma B Wilk

    2009-03-01

    Full Text Available The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1/FVC is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs associated with the FEV(1/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV(1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09. One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV(1/FVC (p-value = 2.0e-04. The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G associated with higher FEV(1/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV(1 and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV(1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.

  11. Robust tests for matched case-control genetic association studies

    Directory of Open Access Journals (Sweden)

    Fung Wing

    2010-10-01

    Full Text Available Abstract Background The Cochran-Armitage trend test (CATT is powerful in detecting association between a susceptible marker and a disease. This test, however, may suffer from a substantial loss of power when the underlying genetic model is unknown and incorrectly specified. Thus, it is useful to derive tests obtaining the plausible power against all common genetic models. For this purpose, the genetic model selection (GMS and genetic model exclusion (GME methods were proposed recently. Simulation results showed that GMS and GME can obtain the plausible power against three common genetic models while the overall type I error is well controlled. Results Although GMS and GME are powerful statistically, they could be seriously affected by known confounding factors such as gender, age and race. Therefore, in this paper, via comparing the difference of Hardy-Weinberg disequilibrium coefficients between the cases and the controls within each sub-population, we propose the stratified genetic model selection (SGMS and exclusion (SGME methods which could eliminate the effect of confounding factors by adopting a matching framework. Our goal in this paper is to investigate the robustness of the proposed statistics and compare them with other commonly used efficiency robust tests such as MAX3 and χ2 with 2 degrees of freedom (df test in matched case-control association designs through simulation studies. Conclusion Simulation results showed that if the mean genetic effect of the heterozygous genotype is between those of the two homozygous genotypes, then the proposed tests and MAX3 are preferred. Otherwise, χ2 with 2 df test may be used. To illustrate the robust procedures, the proposed tests are applied to a real matched pair case-control etiologic study of sarcoidosis.

  12. Sequence imputation of HPV16 genomes for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Benjamin Smith

    Full Text Available Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity.A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica.HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution.Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable resource for future studies of HPV16

  13. A strategy analysis for genetic association studies with known inbreeding

    Directory of Open Access Journals (Sweden)

    del Giacco Stefano

    2011-07-01

    Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is

  14. Amiodarone-Associated Optic Neuropathy: A Nationwide Study.

    Science.gov (United States)

    Cheng, Hui-Chen; Yeh, Huan-Jui; Huang, Nicole; Chou, Yiing-Jenq; Yen, May-Yung; Wang, An-Guor

    2015-12-01

    To investigate whether amiodarone use is associated with an increased risk of optic neuropathy. Retrospective population-based cohort study. Patients newly treated with amiodarone between 2005 and 2009 were identified from the Taiwan National Health Insurance Research Database. For each case patient, the study also included 4 age- and gender-matched control subjects who did not receive amiodarone treatment. Cox multivariate regression analysis was used to assess the association between amiodarone and the occurrence of optic neuropathy. Hazard ratios (HRs) and 95% confidence intervals (CIs). The analysis included 6175 amiodarone-treated patients and 24 700 controls. The mean age was 66.7 years and 55.3% of subjects were male. The mean follow-up was 688 days. During the observational period, optic neuropathy developed in 17 amiodarone-treated patients (0.3%) and 30 control patients (0.1%; P = 0.006). Multivariate Cox regression analysis showed that amiodarone-treated patients had a 2-fold increased risk of optic neuropathy (HR, 2.09; 95% CI, 1.13-3.85; P = 0.02). After stratification by gender, amiodarone use remained a significant factor for optic neuropathy development among male subjects (HR, 3.05; 95% CI, 1.42-6.55; P = 0.004), but not among female subjects (HR, 1.15; 95% CI, 0.38-3.47; P = 0.81). Among amiodarone-treated patients, male gender was associated with a nearly 3-fold increased risk of optic neuropathy development compared with female gender (HR, 2.91; 95% CI, 0.94-9.01; P = 0.06). We also detected a trend of increased cumulative incidence of optic neuropathy with longer treatment duration (>41 vs. ≤41 days; HR, 3.46; 95% CI, 0.99-12.07; P = 0.05). However, higher daily dose did not increase the risk of optic neuropathy (HR, 0.96; 95% CI, 0.91-1.00; P = 0.07). These results demonstrated a higher risk of optic neuropathy in patients treated with amiodarone, especially in males and possibly in patients with longer duration of treatment. Copyright

  15. Athletes and eating disorders: the National Collegiate Athletic Association study.

    Science.gov (United States)

    Johnson, C; Powers, P S; Dick, R

    1999-09-01

    To present findings from a collaborative study with the National College Athletic Association regarding the prevalence of disordered eating among student athletes. 1,445 student athletes from 11 Division 1 schools were surveyed using a 133-item questionnaire. Results indicated that 1.1% of the females met DSM-IV criteria for bulimia nervosa versus 0% for males. None of the student athletes met DSM-IV criteria for anorexia nervosa. 9.2% of the females were identified as having clinically significant problems with bulimia versus .01% of the males. 2.85% of the females were identified as having a clinically significant problem with anorexia nervosa versus 0% for males. 10.85% of the females reported binge eating on a weekly or greater basis versus 13.02% of the males 5.52% of the females reported purging behavior (vomiting, laxatives, diuretics) on a weekly or greater basis versus 2.04% for the males. Results from the current investigation are more conservative than previous studies of student athletes, but comparable to another large study of elite Norwegian athletes. Reasons for these differences are discussed. Clearly female athletes report more difficulty with disordered eating than male athletes. Some specific risk factors for female athletes are discussed.

  16. Genome-wide association study of polymorphisms predisposing to bronchiolitis

    NARCIS (Netherlands)

    Pasanen, Anu; Karjalainen, Minna K.; Bont, Louis|info:eu-repo/dai/nl/304813370; Piippo-Savolainen, Eija; Ruotsalainen, Marja; Goksör, Emma; Kumawat, Kuldeep; Hodemaekers, Hennie M; Nuolivirta, Kirsi; Jartti, Tuomas; Wennergren, Göran; Hallman, Mikko; Rämet, Mika; Korppi, Matti

    2017-01-01

    Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a

  17. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

    NARCIS (Netherlands)

    Natarajan, Pradeep; Bis, Joshua C; Bielak, Lawrence F; Cox, Amanda J; Dörr, Marcus; Feitosa, Mary F; Franceschini, Nora; Guo, Xiuqing; Hwang, Shih-Jen; Isaacs, Aaron; Jhun, Min A; Kavousi, Maryam; Li-Gao, Ruifang; Lyytikäinen, Leo-Pekka; Marioni, Riccardo E; Schminke, Ulf; Stitziel, Nathan O; Tada, Hayato; van Setten, Jessica|info:eu-repo/dai/nl/345493990; Smith, Albert V; Vojinovic, Dina; Yanek, Lisa R; Yao, Jie; Yerges-Armstrong, Laura M; Amin, Najaf; Baber, Usman; Borecki, Ingrid B; Carr, J Jeffrey; Chen, Yii-Der Ida; Cupples, L Adrienne; de Jong, Pim A|info:eu-repo/dai/nl/287955672; de Koning, Harry; de Vos, Bob D|info:eu-repo/dai/nl/413986004; Demirkan, Ayse; Fuster, Valentin; Franco, Oscar H; Goodarzi, Mark O; Harris, Tamara B; Heckbert, Susan R; Heiss, Gerardo; Hoffmann, Udo; Hofman, Albert; Išgum, Ivana|info:eu-repo/dai/nl/31484984X; Jukema, J Wouter; Kähönen, Mika; Kardia, Sharon L R; Kral, Brian G; Launer, Lenore J; Massaro, Joseph; Mehran, Roxana; Mitchell, Braxton D; Mosley, Thomas H; de Mutsert, Renée; Newman, Anne B; Nguyen, Khanh-Dung; North, Kari E; O'Connell, Jeffrey R; Oudkerk, Matthijs; Pankow, James S; Peloso, Gina M; Post, Wendy; Province, Michael A; Raffield, Laura M; Raitakari, Olli T; Reilly, Dermot F; Rivadeneira, Fernando; Rosendaal, Frits; Sartori, Samantha; Taylor, Kent D; Teumer, Alexander; Trompet, Stella; Turner, Stephen T; Uitterlinden, André G; Vaidya, Dhananjay; van der Lugt, Aad; Völker, Uwe; Wardlaw, Joanna M; Wassel, Christina L; Weiss, Stefan; Wojczynski, Mary K; Becker, Diane M; Becker, Lewis C; Boerwinkle, Eric; Bowden, Donald W; Deary, Ian J; Dehghan, Abbas; Felix, Stephan B; Gudnason, Vilmundur; Lehtimäki, Terho; Mathias, Rasika; Mook-Kanamori, Dennis O; Psaty, Bruce M; Rader, Daniel J; Rotter, Jerome I; Wilson, James G; van Duijn, Cornelia M; Völzke, Henry; Kathiresan, Sekar; Peyser, Patricia A; O'Donnell, Christopher J

    2016-01-01

    BACKGROUND: -The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease (CHD). We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the

  18. Prevention of healthcare associated infections: a descriptive study.

    Science.gov (United States)

    Accardi, R; Castaldi, S; Marzullo, A; Ronchi, S; Laquintana, D; Lusignani, M

    2017-01-01

    This study aims to verify whether there are, and to which degree, knowledge and adherence to guidelines on the prevention and control of healthcare associated infections by nursing staff. Study design. A descriptive study was conducted on a sample of nurses in the areas of medicine, surgery, and its own specialties of the Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico in Milan from 1st December 2015 to 29th February 2016. The knowledge of the nursing staff have been investigated through the use of questionnaires with anonymous self-reporting method; inspections in the wards using observational grids were carried out in order to verify adherence to best-practice principles. The data collected concern, both for the knowledge and for the practice, the following macro-areas: a) Cleaning, disinfection and sterilization, b) Hand hygiene, c) Standard and isolation precautions, d) Prevention of catheter-related urinary tract infections, e) Prevention of catheter-related bacteremia, f) Prevention of surgical site infections, g) Prevention of respiratory tract infections. Statistical analyzes were performed using Microsoft Office Excel and STATA software. 245 nurses from 16 wards were involved. In each wards 4 inspections were conducted. 128 completed questionnaires were returned, all considered for the analysis of data; the adhesion was 52.2%. The participants achieved an overall score of 15.0 ± 4.1 (mean ± SD) on a maximum achievable score of 23 and >75% of them have reached a sufficient level. Among the most positive results, it must be underlined that nurses have demonstrated a higher level of knowledge for hand hygiene, with >81% correct answers; that the lumens of central venous catheters, when not in use, were kept covered with a protective cap in more than 99% of cases; that, for patients bearers of urinary catheter, the urinary drainage bag was maintained below the level of the bladder, as recommended, in more than 91

  19. Genome-wide Association Study of Personality Traits in the Long Life Family Study

    Directory of Open Access Journals (Sweden)

    Harold T Bae

    2013-05-01

    Full Text Available Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS on personality factors assessed by NEO-FFI in individuals enrolled in the Long Life Family Study (LLFS, a study of 583 families (N up to 4595 with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p<10-8 and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241 failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2X10-7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value < 10-4 and 10-5, were also marginally significantly associated in this study (p-value < 0.05, although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene-gene interactions affecting personality traits and longevity.

  20. Adult Learning Open University Determinants study (ALOUD): physical activity associated with study success

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2013-01-01

    Gijselaers, H. J. M., De Groot, R. H. M., & Kirschner, P. A. (2013, 23 May). Adult Learning Open University Determinants study (ALOUD): physical activity associated with study success. Poster presentation at the annual meeting of the International Society for Behaviour on Nutrition and Physical

  1. Highway Expenditures and Associated Customer Satisfaction: A Case Study

    Directory of Open Access Journals (Sweden)

    Alexander Paz

    2016-01-01

    Full Text Available This study analyzes the satisfaction of the Nevadans with respect to their highway transportation system and the corresponding expenditures of Nevada Department of Transportation (NDOT. A survey questionnaire was designed to capture the opinions of the Nevadans (customers about a number of characteristics of their transportation system. Data from the financial data warehouse of the NDOT was used to evaluate expenditures. Multinomial probit models were estimated to study the correlations between customers’ opinion and the government expenditures in transportation. The results indicate the customer satisfaction is decreasing with respect to traffic safety throughout Northwestern and Southern Nevada highways. In addition, users of Northwestern highways are more likely to be satisfied, compared to their counterparts, with increasing construction spending to reduce the time taken to complete construction projects. In Southern Nevada highways, customers’ satisfaction increases with the expenditures associated with reduction of congestion. These insights are examples of the conclusions that were obtained as a consequence of simultaneously considering customer satisfaction and the corresponding expenditures in transportation.

  2. Genome-wide association study of proneness to anger.

    Science.gov (United States)

    Mick, Eric; McGough, James; Deutsch, Curtis K; Frazier, Jean A; Kennedy, David; Goldberg, Robert J

    2014-01-01

    Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC) study (n = 8,747). Subjects were, on average, 54 (range 45-64) years old at baseline enrollment, 47% (n = 4,117) were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 ± 1.8 and 7.6 ± 2.2. We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected pgc = 2.2E-07, λ = 1.0015) on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn. Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3)-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament.

  3. Genome-wide association study of proneness to anger.

    Directory of Open Access Journals (Sweden)

    Eric Mick

    Full Text Available BACKGROUND: Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. METHODS: With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC study (n = 8,747. RESULTS: Subjects were, on average, 54 (range 45-64 years old at baseline enrollment, 47% (n = 4,117 were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 ± 1.8 and 7.6 ± 2.2. We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected pgc = 2.2E-07, λ = 1.0015 on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn. CONCLUSIONS: Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament.

  4. [Creativity and Character Traits of University Students: Transversal Association Study].

    Science.gov (United States)

    Santamaría, Hernando; Sánchez, Ricardo

    2012-06-01

    This study was carried out to assess the relationship between character traits and creativity in a sample of students from a public university in Bogotá. A random sample of 157 students from the Universidad Nacional de Colombia. The two instruments used for measuring character traits and creativity were the International Personality Disorder Examination (IPDE) and the Abbreviated Torrance Test for Adults (ATTA). Additional information about gender, psychopathological antecedents, current academic period and academic average have been recorded. Robust regression methods have been used to analyze the relationship between creativity and character traits. Creativity and narcissistic traits were associated. In a multivariate model, other variables showing a relationship with creativity were found, i.e., male gender, mental illness family antecedents, number of academic periods completed, and a high academic average. Relationship between creativity and narcissistic traits had not been reported in previous. Longitudinal studies using more accurate scales should be undertaken to determine the validity of these findings. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  5. Genome-wide association study of Tourette Syndrome

    Science.gov (United States)

    Scharf, Jeremiah M.; Yu, Dongmei; Mathews, Carol A.; Neale, Benjamin M.; Stewart, S. Evelyn; Fagerness, Jesen A; Evans, Patrick; Gamazon, Eric; Edlund, Christopher K.; Service, Susan; Tikhomirov, Anna; Osiecki, Lisa; Illmann, Cornelia; Pluzhnikov, Anna; Konkashbaev, Anuar; Davis, Lea K; Han, Buhm; Crane, Jacquelyn; Moorjani, Priya; Crenshaw, Andrew T.; Parkin, Melissa A.; Reus, Victor I.; Lowe, Thomas L.; Rangel-Lugo, Martha; Chouinard, Sylvain; Dion, Yves; Girard, Simon; Cath, Danielle C; Smit, Jan H; King, Robert A.; Fernandez, Thomas; Leckman, James F.; Kidd, Kenneth K.; Kidd, Judith R.; Pakstis, Andrew J.; State, Matthew; Herrera, Luis Diego; Romero, Roxana; Fournier, Eduardo; Sandor, Paul; Barr, Cathy L; Phan, Nam; Gross-Tsur, Varda; Benarroch, Fortu; Pollak, Yehuda; Budman, Cathy L.; Bruun, Ruth D.; Erenberg, Gerald; Naarden, Allan L; Lee, Paul C; Weiss, Nicholas; Kremeyer, Barbara; Berrío, Gabriel Bedoya; Campbell, Desmond; Silgado, Julio C. Cardona; Ochoa, William Cornejo; Restrepo, Sandra C. Mesa; Muller, Heike; Duarte, Ana V. Valencia; Lyon, Gholson J; Leppert, Mark; Morgan, Jubel; Weiss, Robert; Grados, Marco A.; Anderson, Kelley; Davarya, Sarah; Singer, Harvey; Walkup, John; Jankovic, Joseph; Tischfield, Jay A.; Heiman, Gary A.; Gilbert, Donald L.; Hoekstra, Pieter J.; Robertson, Mary M.; Kurlan, Roger; Liu, Chunyu; Gibbs, J. Raphael; Singleton, Andrew; Hardy, John; Strengman, Eric; Ophoff, Roel; Wagner, Michael; Moessner, Rainald; Mirel, Daniel B.; Posthuma, Danielle; Sabatti, Chiara; Eskin, Eleazar; Conti, David V.; Knowles, James A.; Ruiz-Linares, Andres; Rouleau, Guy A.; Purcell, Shaun; Heutink, Peter; Oostra, Ben A.; McMahon, William; Freimer, Nelson; Cox, Nancy J.; Pauls, David L.

    2012-01-01

    Tourette Syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel, and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (p<5 × 10−8); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (p=1.85 × 10−6). A secondary analysis including an additional 211 cases and 285 controls from two closely-related Latin-American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal (p=3.6 × 10−7 for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder. PMID:22889924

  6. Study of outcomes associated with hyponatremia and hypernatremia in children.

    Science.gov (United States)

    Guarner, Jeannette; Hochman, Jay; Kurbatova, Ekaterina; Mullins, Richard

    2011-01-01

    Sodium is usually included in hospitals' critical values lists; however, the values at which sodium is considered to be life threatening (critical) vary among hospitals. Studies of outcomes associated with hyponatremia and hypernatremia in pediatric patients have not been published. We performed a retrospective chart review of sodium values of 155 mmol/L that occurred during a 6-month period. Univariate and multivariate analyses for mortality risk were performed with the different variables. A total of 702 (1.32%) sodium tests fell in the study reference range, with 166 being 155 mmol/L. Although not statistically significant, mortality was higher (38.5%) in patients with sodium values ≤ 120 mmol/L than in those with values ≥ 170 mmol/L (25%) or in patients with other values (hypernatremia. Treatment was instituted within 4 hours in 80% of cases (50% within 1 hour). Multivariate analysis showed increased risk of death for hyponatremic patients if they were premature or had heart abnormalities, while for hypernatremic patients the risk increased when other critical values were present. In conclusion, sodium levels of ≤ 120 mmol/L and ≥ 170 mmol/L have increased mortality in children; however, the risk of death is not statistically different when compared to risk in patients with milder hyponatremia and hypernatremia. Risk factors for death in hyponatremic and hypernatremic patients may primarily reflect the severity of the underlying conditions present in these children, such as prematurity and heart abnormalities, rather than the sodium derangement.

  7. Association study of the NF1 gene and autistic disorder.

    Science.gov (United States)

    Mbarek, O; Marouillat, S; Martineau, J; Barthélémy, C; Müh, J P; Andres, C

    1999-12-15

    Neurofibromatosis type 1 (NF1) is increased about 150-fold in autistic patients. The aim of this study was to test for an association between the NF1 locus and autistic disorder. The allele distributions of three markers of the NF1 gene were studied in 85 autistic patients and 90 controls. No differences in allele distributions were observed. However, we found a new allele (allele 5) of the GXAlu marker in four autistic patients. Allele 5 was absent in a larger control population (213 individuals). The patients with allele 5 had a more severe clinical picture, mainly in the fields of motility and tonus. Our preliminary results suggest that the NF1 region is not a major susceptibility locus for autism. However, the GXAlu marker of the NF1 gene appears as a possible candidate for a susceptibility locus in a small subgroup of severely affected autistic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:729-732, 1999. Copyright 1999 Wiley-Liss, Inc.

  8. [Pregnancy-Associated Breast Cancer: An analytical observational study].

    Science.gov (United States)

    Baulies, Sonia; Cusidó, Maite; Tresserra, Francisco; Rodríguez, Ignacio; Ubeda, Belén; Ara, Carmen; Fábregas, Rafael

    2014-03-04

    Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade iii, as well as a delay in diagnosis with a higher rate of advanced stages. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  9. Genome-wide association study of schizophrenia in Japanese population.

    Directory of Open Access Journals (Sweden)

    Kazuo Yamada

    Full Text Available Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions. The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila-like 2] gene located on 9p21.3 (p = 0.00087. In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026. The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology.

  10. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

    Directory of Open Access Journals (Sweden)

    Toshiko Tanaka

    2009-01-01

    Full Text Available Polyunsaturated fatty acids (PUFA have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3. The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95 x 10(-46. Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78 x 10(-9 and eicosapentanoic acid (EPA; p = 1.07 x 10(-14. Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2. In this region, association was observed with EPA (rs953413; p = 1.1 x 10(-6. The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.

  11. Prevalence of anaemia associated with chronic obstructive pulmonary disease. Study of associated variables.

    Science.gov (United States)

    Comeche Casanova, Lorena; Echave-Sustaeta, Jose María; García Luján, Ricardo; Albarrán Lozano, Irene; Alonso González, Pablo; Llorente Alonso, María Jesús

    2013-09-01

    Anaemia is one of the extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). Its real prevalence, physiopathology and clinical repercussion are unknown. The objectives of our study were: to determine the prevalence of anaemia in patients with stable COPD not attributable to other causes and to establish the relationship of anaemia with clinical, prognostic and inflammatory markers with an important role in COPD. The study included stable COPD patients with no other known causes of anaemia. The following tests were carried out: respiratory function tests; serum determination of erythropoietin and inflammatory markers: high sensitivity C-reactive protein (hs-CRP), fibrinogen, interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor α (TNF-α). Body mass index (BMI), Charlson and BODE indices, the number of exacerbations in the previous year, dyspnoea and quality of life were also calculated. One hundred and thirty patients were included. Anaemia prevalence was 6.2%. Mean haemoglobin value in anaemic patients was 11.9±0.95g/dL. Patients with anaemia had a lower BMI (P=.03), higher Charlson index (P=.002), more elevated erythropoietin levels (P=.016), a tendency to present a lower FEV1% value (P=.08) and significantly lower IL-6 values when compared to non-anaemic patients (P=.003). In our series, the anaemia associated with COPD was less prevalent than that published in the literature to date, and was related to certain clinical and inflammatory markers. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  12. 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]O...

  13. Genome-wide association study of sporadic brain arteriovenous malformations

    National Research Council Canada - National Science Library

    Weinsheimer, S; Bendjilali, N; Nelson, J; Guo, D.E; Zaroff, J.G; Sidney, S; McCulloch, C.E; Salman, R. Al-Shahi; Berg, J.N; Koeleman, B.P.C; Simon, M; Bostroem, A; Fontanella, M; Sturiale, C.L; Pola, R; Puca, A; Lawton, M.T; Young, W.L; Pawlikowska, L; Klijn, C.J.M; Kim, H

    2016-01-01

    ...) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. METHODS...

  14. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies

    DEFF Research Database (Denmark)

    Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L

    2011-01-01

    Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.......Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors....

  15. An ecophysiological study of the Azolla filiculoides- Anabaena azollae association

    Science.gov (United States)

    van Kempen, Monique; Smolders, Fons; Speelman, Eveline; Reichart, Gert Jan; Barke, Judith; Brinkhuis, Henk; Lotter, Andy; Roelofs, Jan

    2010-05-01

    The long term effects of salinity stress on the growth, nutrient content and amino acid composition of the Azolla filiculoides - Anabaena azollae association was studied in a laboratory experiment. It was demonstrated that the symbiosis could tolerate salt stress up to 90 mM NaCl, even after a 100 day period of preconditioning at salt concentrations that were 30 mM NaCl lower. In the 120 mM NaCl treatment the Azolla filiculoides survived, but hardly any new biomass was produced. It was shown that during the experiment, A. filiculoides became increasingly efficient in excluding salt ions from the plant tissue and was thus able to increase its salt tolerance. The amino acid analysis revealed that the naturally occurring high glutamine concentration in the plants was strongly reduced at salt concentrations of 120 mM NaCl and higher. This was the result of the reduced nitrogenase activity at these salt concentrations, as was demonstrated in an acetylene reduction assay. We suggest that the high glutamine concentration in the plants might play a role in the osmoregulatory response against salt stress, enabling growth of the A. filiculoides -Anabaena azollae association up to 90 mM NaCl. In a mesocosm experiment it furthermore was demonstrated that Azolla might manipulate its own microenvironment when grown at elevated salt concentration (up to ~50 mmol•L-1) by promoting salinity stratification, especially when it has formed a dense cover at the water surface. Beside salt stress, we also studied the growth of Azolla filiculoides in response to elevated atmospheric carbon dioxide concentration, in combination with different light intensities and different pH of the nutrient solution. The results demonstrated that as compared to the control (ambient pCO2 concentrations), Azolla filiculoides was able to produce twice as much biomass at carbon dioxide concentrations that were five times as high as the ambient pCO2 concentration. However, it was also shown that this

  16. Study of acoustic correlates associate with emotional speech

    Science.gov (United States)

    Yildirim, Serdar; Lee, Sungbok; Lee, Chul Min; Bulut, Murtaza; Busso, Carlos; Kazemzadeh, Ebrahim; Narayanan, Shrikanth

    2004-10-01

    This study investigates the acoustic characteristics of four different emotions expressed in speech. The aim is to obtain detailed acoustic knowledge on how a speech signal is modulated by changes from neutral to a certain emotional state. Such knowledge is necessary for automatic emotion recognition and classification and emotional speech synthesis. Speech data obtained from two semi-professional actresses are analyzed and compared. Each subject produces 211 sentences with four different emotions; neutral, sad, angry, happy. We analyze changes in temporal and acoustic parameters such as magnitude and variability of segmental duration, fundamental frequency and the first three formant frequencies as a function of emotion. Acoustic differences among the emotions are also explored with mutual information computation, multidimensional scaling and acoustic likelihood comparison with normal speech. Results indicate that speech associated with anger and happiness is characterized by longer duration, shorter interword silence, higher pitch and rms energy with wider ranges. Sadness is distinguished from other emotions by lower rms energy and longer interword silence. Interestingly, the difference in formant pattern between [happiness/anger] and [neutral/sadness] are better reflected in back vowels such as /a/(/father/) than in front vowels. Detailed results on intra- and interspeaker variability will be reported.

  17. Genome-wide association study of working memory brain activation.

    Science.gov (United States)

    Blokland, Gabriëlla A M; Wallace, Angus K; Hansell, Narelle K; Thompson, Paul M; Hickie, Ian B; Montgomery, Grant W; Martin, Nicholas G; McMahon, Katie L; de Zubicaray, Greig I; Wright, Margaret J

    2017-05-01

    In a population-based genome-wide association (GWA) study of n-back working memory task-related brain activation, we extracted the average percent BOLD signal change (2-back minus 0-back) from 46 regions-of-interest (ROIs) in functional MRI scans from 863 healthy twins and siblings. ROIs were obtained by creating spheres around group random effects analysis local maxima, and by thresholding a voxel-based heritability map of working memory brain activation at 50%. Quality control for test-retest reliability and heritability of ROI measures yielded 20 reliable (r>0.7) and heritable (h(2)>20%) ROIs. For GWA analysis, the cohort was divided into a discovery (n=679) and replication (n=97) sample. No variants survived the stringent multiple-testing-corrected genome-wide significance threshold (pmemory. Variants identified here may be relevant to (the susceptibility to) common disorders affecting brain function. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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...

  19. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger

    2009-01-01

    cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1...... ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially......Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive...

  20. A Whole Genome Association Study on Meat Palatability in Hanwoo

    Directory of Open Access Journals (Sweden)

    K.-E. Hyeong

    2014-09-01

    Full Text Available A whole genome association (WGA study was carried out to find quantitative trait loci (QTL for sensory evaluation traits in Hanwoo. Carcass samples of 250 Hanwoo steers were collected from National Agricultural Cooperative Livestock Research Institute, Ansung, Gyeonggi province, Korea, between 2011 and 2012 and genotyped with the Affymetrix Bovine Axiom Array 640K single nucleotide polymorphism (SNP chip. Among the SNPs in the chip, a total of 322,160 SNPs were chosen after quality control tests. After adjusting for the effects of age, slaughter-year-season, and polygenic effects using genome relationship matrix, the corrected phenotypes for the sensory evaluation measurements were regressed on each SNP using a simple linear regression additive based model. A total of 1,631 SNPs were detected for color, aroma, tenderness, juiciness and palatability at 0.1% comparison-wise level. Among the significant SNPs, the best set of 52 SNP markers were chosen using a forward regression procedure at 0.05 level, among which the sets of 8, 14, 11, 10, and 9 SNPs were determined for the respectively sensory evaluation traits. The sets of significant SNPs explained 18% to 31% of phenotypic variance. Three SNPs were pleiotropic, i.e. AX-26703353 and AX-26742891 that were located at 101 and 110 Mb of BTA6, respectively, influencing tenderness, juiciness and palatability, while AX-18624743 at 3 Mb of BTA10 affected tenderness and palatability. Our results suggest that some QTL for sensory measures are segregating in a Hanwoo steer population. Additional WGA studies on fatty acid and nutritional components as well as the sensory panels are in process to characterize genetic architecture of meat quality and palatability in Hanwoo.

  1. Molecular evaluation of genetic diversity and association studies in ...

    Indian Academy of Sciences (India)

    Low linkage disequilibrium of landforms suggests their narrow adaptation in local geographical niche. Many population specific alleles could be identified particularly for japonica cultivars and landraces. Association analysis revealed nine marker–trait associations with three agronomic traits, of which 67% were previously ...

  2. A systematic analysis of the association studies between CASP8 ...

    Indian Academy of Sciences (India)

    Yinliang Zhang

    2017-06-17

    Jun 17, 2017 ... Abstract. Caspase 8 (CASP8) is a regulator of apoptosis, whose genetic variation has been reported to be associated with the risk of various cancers. Especially, the single-nucleotide polymorphism (SNP) rs1045485, which generates the substitution. D302H in CASP8, is likely to be associated with breast ...

  3. A systematic analysis of the association studies between CASP8 ...

    Indian Academy of Sciences (India)

    Caspase 8 (CASP8) is a regulator of apoptosis, whose genetic variation has been reported to be associated with the risk of various cancers. Especially, the single-nucleotide polymorphism (SNP) rs1045485, which generates the substitution D302H in CASP8, is likely to be associated with breast cancer. Several previous ...

  4. Susceptibility to chronic mucus hypersecretion, a genome wide association study

    NARCIS (Netherlands)

    A.E. Dijkstra (Akkelies); J. Smolonska (Joanna); M. van den Berge (Maarten); C. Wijmenga (Ciska); P. Zanen (Pieter); M.A. Luinge (Marjan); I. Platteel (Inge); J.-W.J. Lammers (Jan-Willem); M. Dahlback (Magnus); K. Tosh (Kerrie); P.S. Hiemstra (Pieter); P.J. Sterk (Peter); M.E. Spira (Micha); J. Vestbo (Jorgen); B.G. Nordestgaard (Børge); M. Benn (Marianne); S.F. Nielsen (Sune); M. Dahl (Morten); W.M.M. Verschuren (W. M. Monique); H.S.J. Picavet (Susan); H.A. Smit (Henriëtte); M. Owsijewitsch (Michael); H.U. Kauczor (Hans); H.J. de Koning (Harry); E. Nizankowska-Mogilnicka (Eva); F. Mejza (Filip); P. Nastalek (Pawel); C.C. van Diemen (Cleo); M.H. Cho (Michael); E.K. Silverman (Edwin); R.O. Crapo (Robert); T.H. Beaty (Terri); D.J. Lomas (David John); A.B. Bakke (Arnold B.); A. Gulsvik (Amund); Y. Bossé (Yohan); M. Obeidat; D.W. Loth (Daan); L. Lahousse (Lies); F. Rivadeneira Ramirez (Fernando); A.G. Uitterlinden (André); A. Hofman (Albert); B.H.Ch. Stricker (Bruno); G.G. Brusselle (Guy); C.M. van Duijn (Cornelia); U. Brouwer (Uilke); G.H. Koppelman (Gerard); J.M. Vonk (Judith); M.C. Nawijn (Martijn); H.J.M. Groen (Henk); W. Timens (Wim); H.M. Boezen (Marike); D.S. Postma (Dirkje); B.Z. Alizadeh (Behrooz); R.A. de Boer (Rudolf); M. Bruinenberg (M.); L. Franke (Lude); P. van der Harst (Pim); H.L. Hillege (Hans); M.M. van der Klauw (Melanie); G. Navis (Gerjan); J. Ormel (Johan); J.G.M. Rosmalen (Judith); J.P.J. Slaets (Joris); H. Snieder (Harold); R.P. Stolk (Ronald); B. Wolffenbuttel (Bhr)

    2014-01-01

    textabstractBackground: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a

  5. Susceptibility to chronic mucus hypersecretion, a genome wide association study

    NARCIS (Netherlands)

    Dijkstra, Akkelies E.; Smolonska, Joanna; van den Berge, Maarten; Wijmenga, Cisca; Zanen, Pieter; Luinge, Marjan A.; Platteel, Mathieu; Lammers, Jan-Willem; Dahlback, Magnus; Tosh, Kerrie; Hiemstra, Pieter S.; Sterk, Peter J.; Spira, Avi; Vestbo, Jorgen; Nordestgaard, Borge G.; Benn, Marianne; Nielsen, Sune F.; Dahl, Morten; Verschuren, W. Monique; Picavet, H. Susan J.; Smit, Henriette A.; Owsijewitsch, Michael; Kauczor, Hans U.; de Koning, Harry J.; Nizankowska-Mogilnicka, Eva; Mejza, Filip; Nastalek, Pawel; van Diemen, Cleo C.; Cho, Michael H.; Silverman, Edwin K.; Crapo, James D.; Beaty, Terri H.; Lomas, David A.; Bakke, Per; Gulsvik, Amund; Bosse, Yohan; Obeidat, M. A.; Loth, Daan W.; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Andre; Stricker, Bruno H.; Brusselle, Guy G.; van Duijn, CorneliaM.; Brouwer, Uilke; Koppelman, Gerard H.; Vonk, Judith M.; Nawijn, Martijn C.; Groen, Harry J.M.; Timens, Wim; Boezen, Hendrika; Postma, Dirkje S.

    2014-01-01

    Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of

  6. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis

    NARCIS (Netherlands)

    Natarajan, Pradeep; Bis, Joshua C.; Bielak, Lawrence F.; Cox, Amanda J.; Dorr, Marcus; Feitosa, Mary F.; Franceschini, Nora; Guo, Xiuqing; Hwang, Shih-Jen; Isaacs, Aaron; Jhun, Min A.; Kavousi, Maryam; Li-Gao, Ruifang; Lyytikainen, Leo-Pekka; Marioni, Riccardo E.; Schminke, Ulf; Stitziel, Nathan O.; Tada, Hayato; van Setten, Jessica; Smith, Albert V.; Vojinovic, Dina; Yanek, Lisa R.; Yao, Jie; Yerges-Armstrong, Laura M.; Amin, Najaf; Baber, Usman; Borecki, Ingrid B.; Carr, J. Jeffrey; Chen, Yii-Der Ida; Cupples, L. Adrienne; de Jong, Pim A.; de Koning, Harry; de Vos, Bob D.; Demirkan, Ayse; Fuster, Valentin; Franco, Oscar H.; Goodarzi, Mark O.; Harris, Tamara B.; Heckbert, Susan R.; Heiss, Gerardo; Hoffmann, Udo; Hofman, Albert; Isgum, Ivana; Jukema, J. Wouter; Kahonen, Mika; Kardia, Sharon L. R.; Kral, Brian G.; Launer, Lenore J.; Massaro, Joe; Mehran, Roxana; Mitchell, Braxton D.; Jr, Thomas H. Mosley; de Mutsert, Renee; Newman, Anne B.; Nguyen, Khanh-dung; North, Kari E.; O'Connell, Jeffrey R.; Oudkerk, Matthijs; Pankow, James S.; Peloso, Gina M.; Post, Wendy; Province, Michael A.; Raffield, Laura M.; Raitakari, Olli T.; Reilly, Dermot F.; Rivadeneira, Fernando; Rosendaal, Frits; Sartori, Samantha; Taylor, Kent D.; Teumer, Alexander; Trompet, Stella; Turner, Stephen T.; Uitterlinden, Andre G.; Vaidya, Dhananjay; van der Lugt, Aad; Volker, Uwe; Wardlaw, Joanna M.; Wassel, Christina L.; Weiss, Stefan; Wojczynski, Mary K.; Becker, Diane M.; Becker, Lewis C.; Boerwinkle, Eric; Bowden, Donald W.; Deary, Ian J.; Dehghan, Abbas; Felix, Stephan B.; Gudnason, Vilmundur; Lehtimaki, Terho; Mathias, Rasika; Mook-Kanamori, Dennis O.; Psaty, Bruce M.; Rader, Daniel J.; Rotter, Jerome I.; Wilson, James G.; van Duijn, Cornelia M.; Volzke, Henry; Kathiresan, Sekar; Peyser, Patricia A.; O'Donnell, Christopher J.

    2016-01-01

    Background-The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of

  7. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact...

  8. Association between cancer and contact allergy: a linkage study

    DEFF Research Database (Denmark)

    Engkilde, Kaare; Thyssen, Jacob P; Menné, Torkil

    2011-01-01

    and cancer, few have looked into the association between cancer and contact allergy, a type IV allergy. By linking two clinical databases, the authors investigate the possible association between contact allergy and cancer. Methods Record linkage of two different registers was performed: (1) a tertiary...... hospital register of dermatitis patients patch tested for contact allergy and (2) a nationwide cancer register (the Danish Cancer Register). After linking the two registers, only cancer subtypes with 40 or more patients registered were included in the analysis. The final associations were evaluated...... by logistic regression analysis. Results An inverse association between contact allergy and non-melanoma skin- and breast cancer, respectively, was identified in both sexes, and an inverse trend for brain cancer was found in women with contact allergy. Additionally, a positive association between contact...

  9. Association between diabetes and tuberculosis: case-control study.

    Science.gov (United States)

    Pereira, Susan Martins; Araújo, Gleide Santos de; Santos, Carlos Antônio de Souza Teles; Oliveira, Maeli Gomes de; Barreto, Maurício Lima

    2016-12-22

    To test the association between diabetes and tuberculosis. It is a case-control study, matched by age and sex. We included 323 new cases of tuberculosis with positive results for bacilloscopy. The controls were 323 respiratory symptomatic patients with negative bacilloscopy, from the same health services, such as: ambulatory cases from three referral hospitals and six basic health units responsible for the notifications of new cases of tuberculosis in Salvador, Bahia. Data collection occurred between 2008 and 2010. The instruments used were structured interview, including clinical data, capillary blood glucose (during fasting or postprandial), and the CAGE questionnaire for screening of abusive consumption of alcohol. Descriptive, exploratory, and multivariate analysis was performed using conditional logistic regression. The average age of the cases was 38.5 (SD = 14.2) years and of the controls, 38.5 (SD = 14.3) years. Among cases and controls, most subjects (61%) were male. In univariate analysis we found association between the occurrence of diabetes and tuberculosis (OR = 2.37; 95%CI 1.04-5.42), which remained statistically significant after adjustment for potential confounders (OR = 3.12; 95%CI 1.12-7.94). The association between diabetes and tuberculosis can hinder the control of tuberculosis, contributing to the maintainance of the disease burden. The situation demands increasing early detection of diabetes among people with tuberculosis, in an attempt to improve disease control strategies. Testar a associação entre diabetes e tuberculose. Trata-se de estudo caso-controle, pareado por idade e sexo. Foram incluídos 323 casos novos de tuberculose com resultados positivos à baciloscopia. Os controles foram 323 sintomáticos respiratórios com baciloscopia negativa, oriundos dos mesmos serviços de saúde dos casos: ambulatórios de três hospitais de referência e seis unidades básicas de saúde responsáveis pelas notificações dos casos novos de

  10. A Genomewide Association Study of Early Spontaneous Preterm Delivery

    Science.gov (United States)

    Zhang, Heping; Baldwin, Don A.; Bukowski, Radek K.; Parry, Samuel; Xu, Yaji; Song, Chi; Andrews, William W.; Saade, George R.; Esplin, M. Sean; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John; Varner, Michael; Biggio, Joseph R.

    2015-01-01

    Preterm birth is the leading cause of infant morbidity and mortality. Despite extensive research, the genetic contributions to spontaneous preterm birth (SPTB) are not well understood. Term controls were matched with cases by race/ethnicity, maternal age, and parity prior to recruitment. Genotyping was performed using Affymetrix SNP Array 6.0 assays. Statistical analyses utilized PLINK to compare allele occurrence rates between case and control groups, and incorporated quality control and multiple-testing adjustments. We analyzed DNA samples from mother-infant pairs from early SPTB cases (200/7 to 336/7 weeks, 959 women and 979 neonates) and term delivery controls (390/7 to 416/7 weeks, 960 women and 985 neonates). For validation purposes, we included an independent validation cohort consisting of early SPTB cases (293 mothers and 243 infants) and term controls (200 mothers and 149 infants). Clustering analysis revealed no population stratification. Multiple maternal SNPs were identified with association p-values between 10E-5 and 10E-6. The most significant maternal SNP was rs17053026 on chromosome 3 with an odds ratio (OR) 0.44 with a p-value of 1.0E-06. Two neonatal SNPs reached the genome-wide significance threshold, including rs17527054 on chromosome 6p22 with a p-value of 2.7E-12 and rs3777722 on chromosome 6q27 with a p-value of 1.4E-10. However, we could not replicate these findings after adjusting for multiple comparisons in a validation cohort. This is the first report of a genomewide case-control study to identify single nucleotide polymorphisms (SNPs) that correlate with SPTB. PMID:25599974

  11. Immunohistochemical study of porcine lung lesions associated with Pasteurella multocida

    DEFF Research Database (Denmark)

    Pors, Susanne Elisabeth; Hansen, Mette Sif; Bisgaard, Magne

    2013-01-01

    Infectious bronchopneumonia is a widespread disease in modern commercial pig production and Pasteurella multocida is frequently associated with the lesions. To evaluate porcine lung lesions associated with P. multocida, populations of inflammatory cells were examined by immunohistochemistry...... by immunohistochemistry were T-lymphocytes (CD3(+), CD4(+) and CD8(+) subsets), B-lymphocytes, neutrophils, macrophages, and IgA(+), IgM(+) and IgG(+) cells. The results showed that (1) a significant increase in all inflammatory cells was found in lesions associated with P. multocida, (2) necrotic lesions had a larger....... The results show that P. multocida significantly alters the inflammatory response in the lung and that lesions associated with P. multocida display diverse inflammatory responses according to their distinct morphological pattern....

  12. Clinical and molecular studies in ANCA associated vasculitis

    OpenAIRE

    Wendt, Mårten

    2014-01-01

    ANCA associated vasculitis (AAV) is a heterogeneous group of diseases characterised by sterile pauci-immune systemic small vessel inflammation and closely associated with the presence of anti-neutrophil cytoplasmatic antibodies (ANCA). Although AAV can affect any organ, the kidney, skin, lungs and upper and lower airways are most commonly involved. In some patients there is granuloma formation and in some asthma and eosinophilia, and based on this patients can be further classi...

  13. Factors associated with adolescent cigarette smoking in Greece: Results from a cross sectional study (GYTS Study

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos

    2008-09-01

    Full Text Available Abstract Background Data about the predictors of smoking among adolescents in Greece are sparse. We tried to identify factors associated with current cigarette smoking among in-school adolescents in Greece in the context of GYTS study. Methods A secondary analysis of data from a questionnaire study using the Global Youth Tobacco Survey methodology was conducted to identify factors associated with smoking among adolescents in Greece. Data were collected in 2004–2005. The outcome variable was cigarette smoking within the past 30 days preceding the survey while independent variables included age, gender, parental educational status, parental smoking, perception of harmfulness of smoking, and the amount of pocket money at the adolescent's disposal. Results 6141 adolescents (51.5% males and 48.5% females participated in the study. In multivariate analysis, cigarette smoking was associated with male gender (OR: 1.62; 95% CI: 1, 08–3.08, parental smoking (OR: 2.59; 95% CI: 1.45–5.89, and having pocket money ≥ 16 Euros (OR: 2.64; 95% CI: 1.19–5.98. Conclusion Male gender, parental smoking, and having pocket-money ≥ 16 Euros were independently associated with current smoking among Greek students. These findings could be taken into account in order to formulate a comprehensive anti-smoking strategy in Greece.

  14. Association Between Sleep Timing, Obesity, Diabetes: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Cohort Study.

    Science.gov (United States)

    Knutson, Kristen L; Wu, Donghong; Patel, Sanjay R; Loredo, Jose S; Redline, Susan; Cai, Jianwen; Gallo, Linda C; Mossavar-Rahmani, Yasmin; Ramos, Alberto R; Teng, Yanping; Daviglus, Martha L; Zee, Phyllis C

    2017-04-01

    Recent studies implicate inadequate sleep duration and quality in metabolic disease. Fewer studies have examined the timing of sleep, which may be important because of its potential impact on circadian rhythms of metabolic function. We examined the association between sleep timing and metabolic risk among Hispanic/Latino adults. Cross-sectional data from community-based study of 13429 participants aged 18-74 years. People taking diabetic medications were excluded. Sleep timing was determined from self-reported bedtimes and wake times. Chronotype was defined as the midpoint of sleep on weekends adjusted for sleep duration on weekdays. Other measurements included body mass index (BMI), fasting glucose levels, estimated insulin resistance (HOMA-IR), glucose levels 2 hours post oral glucose ingestion, and hemoglobin A1c. Survey linear regression models tested associations between sleep timing and metabolic measures. Analyses were stratified by diabetes status and age-group when significant interactions were observed. Among participants with diabetes, fasting glucose levels were positively associated with bedtime (approximately +3%/hour later, p sleep (approximately +2%/hour later, p sleep (+1.5%/hr later, p sleep timing was associated with lower BMI, lower fasting glucose, and lower HbA1c, but the opposite association was observed among older participants. Later sleep timing was associated with higher estimated insulin resistance across all groups. Some associations between sleep timing and metabolic measures may be age-dependent.

  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 associated...... tonsillitis (OR=1.19; p=7.82×10(-4)), chronic disease of the tonsils (OR=1.19; p=2.32×10(-6)) and appendectomy (OR=1.18; p=1.13×10(-3)). CONCLUSIONS: We identified and replicated a genetic association at 22q12.2 with tonsillectomy. Further functional investigation is required to illuminate whether...

  16. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    NARCIS (Netherlands)

    E. Evangelou (Evangelos); J.M. Kerkhof (Hanneke); U. Styrkarsdottir (Unnur); E.E. Ntzani (Evangelia); S.D. Bos (Steffan); T. Esko (Tõnu); D.S. Evans (Daniel); S. Metrustry (Sarah); K. Panoutsopoulou (Kalliope); Y.F.M. Ramos (Yolande); G. Thorleifsson (Gudmar); K.K. Tsilidis (Konstantinos); N.K. Arden (Nigel); N. Aslam (Nadim); N. Bellamy (Nicholas); F. Birrell (Fraser); Blanco, F.J. (Francisco J.); A.J. Carr (Andrew Jonathan); K. Chapman (Kay); A.G. Day-Williams (Aaron); P. Deloukas (Panagiotis); M. Doherty (Michael); G. Engström; H.T. Helgadottir (Hafdis); A. Hofman (Albert); T. Ingvarsson (Torvaldur); H. Jonsson (Helgi); A. Keis (Aime); J.C. Keurentjes (J. Christiaan); M. Kloppenburg (Margreet); P.A. Lind (Penelope); A. McCaskie (Andrew); N.G. Martin (Nicholas); L. Milani (Lili); G.W. Montgomery (Grant); R.G.H.H. Nelissen (Rob); M.C. Nevitt (Michael); P. Nilsson (Peter); W.E.R. Ollier (William); N. Parimi (Neeta); A. Rai (Ashok); S.H. Ralston (Stuart); M.R. Reed (Mike); J.A. Riancho (José); F. Rivadeneira Ramirez (Fernando); C. Rodriguez-Fontenla (Cristina); L. Southam (Lorraine); U. Thorsteinsdottir (Unnur); A. Tsezou (Aspasia); G.A. Wallis (Gillian); J.M. Wilkinson (Mark); A. Gonzalez (Antonio); N.E. Lane; L.S. Lohmander (Stefan); J. Loughlin (John); A. Metspalu (Andres); A.G. Uitterlinden (André); I. Jonsdottir (Ingileif); J-A. Zwart (John-Anker); P.E. Slagboom (Eline); E. Zeggini (Eleftheria); I. Meulenbelt (Ingrid); J.P.A. Ioannidis (John); T.D. Spector (Timothy); J.B.J. van Meurs (Joyce); A.M. Valdes (Ana Maria)

    2014-01-01

    textabstractOBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.METHODS: We performed a two-stage meta-analysis

  17. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    NARCIS (Netherlands)

    E. Evangelou (Evangelos); J.M. Kerkhof (Hanneke); U. Styrkarsdottir (Unnur); E.E. Ntzani (Evangelia); S.D. Bos (Steffan); T. Esko (Tõnu); D.S. Evans (Daniel); S. Metrustry (Sarah); K. Panoutsopoulou (Kalliope); Y.F.M. Ramos (Yolande); G. Thorleifsson (Gudmar); K.K. Tsilidis (Konstantinos); N.K. Arden (Nigel); N. Aslam (Nadim); N. Bellamy (Nicholas); F. Birrell (Fraser); F.J. Blanco; A.J. Carr (Andrew Jonathan); K. Chapman (Kay); A.G. Day-Williams (Aaron); P. Deloukas (Panagiotis); M. Doherty (Michael); G. Engström; H.T. Helgadottir (Hafdis); A. Hofman (Albert); T. Ingvarsson (Torvaldur); H. Jonsson (Helgi); A. Keis (Aime); J.C. Keurentjes (J. Christiaan); M. Kloppenburg (Margreet); P.A. Lind (Penelope); A. McCaskie (Andrew); N.G. Martin; A.L. Milani (Alfredo); G.W. Montgomery; R.G.H.H. Nelissen (Rob); M.C. Nevitt (Michael); P. Nilsson (Peter); W.E.R. Ollier (William); N. Parimi (Neeta); A. Rai (Ashok); S.H. Ralston; M.R. Reed (Mike); J.A. Riancho (José); F. Rivadeneira Ramirez (Fernando); C. Rodriguez-Fontenla (Cristina); L. Southam (Lorraine); U. Thorsteinsdottir (Unnur); A. Tsezou (Aspasia); G.A. Wallis (Gillian); J.M. Wilkinson (Mark); A. Gonzalez (Antonio); N.E. Lane; L.S. Lohmander (Stefan); J. Loughlin (John); A. Metspalu (Andres); A.G. Uitterlinden (André); I. Jonsdottir (Ingileif); J-A. Zwart (John-Anker); P.E. Slagboom (Eline); E. Zeggini (Eleftheria); I. Meulenbelt (Ingrid); J.P.A. Ioannidis (John); T.D. Spector (Timothy); J.B.J. van Meurs (Joyce); A.M. Valdes (Ana Maria)

    2014-01-01

    textabstractObjectives: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods: We performed a two-stage meta-analysis

  18. Loci associated with ischaemic stroke and its subtypes (SiGN) : A genome-wide association study

    NARCIS (Netherlands)

    Pulit, SL|info:eu-repo/dai/nl/413970450; Algra, A|info:eu-repo/dai/nl/07483472X; de Bakker, Paul I W|info:eu-repo/dai/nl/342957082

    2016-01-01

    Background: The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and

  19. 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

  20. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

    NARCIS (Netherlands)

    Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; Maloney, Cliona M.; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P. R.; Mehta, Amar; van Iperen, Erik P. A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M. A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; de Boer, Anthonius; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goe, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E. K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshal, Vanessa; Melander, Olle; Mentch, Frank D.; Meyer, Nuala J.; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondah, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszweski, Maciej; Verschuren, W. M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I. W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; Christie, Jason D.; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; Maerz, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Watkins, Hugh; Grant, Struan F. A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Kumari, Meena; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

    2011-01-01

    Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and

  1. 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

  2. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    National Research Council Canada - National Science Library

    ...; Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L; Couch, Fergus J; Nevanlinna, Heli; Milne, Roger L; Gaudet, Mia; Schmidt, Marjanka K; Broeks, Annegien; Cox, Angela; Fasching, Peter A; Hein, Rebecca; Spurdle, Amanda B; Blows, Fiona; ver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J; Van Leeuwen, Flora E; Anulis, Irene L; Glendon, Gord; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Weerasooriya, Nayana; John, Esther M; Beckmann, Matthias W; Hartmann, Arndt; Weihbrecht, Sebastian B; Wachter, David L; Jud, Sebastian M. S; Loehberg, Christian R; Baglietto, Laura; English, Dallas R; Giles, Graham G; McLean, Catriona A; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E; Connley, Daniel; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W. R; Doerk, Thilo; Bremer, Michael; Meyer, Aneas; Karstens, Johann H; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Roiguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M; Tapper, William J; Gerty, Sue M; Sawyer, Elinor J; Tomlinson, Ian P; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios

    2011-01-01

    ...) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  4. A multiple regression method for Genome-wide association study

    Indian Academy of Sciences (India)

    wangzhihua

    ... in various species (Glazner and. Thompson 2015). To improve livestock production and reproduction, genome scanning to detect QTLs associated with economically important traits is an important activity in animal breeding and genetics (Sham and. Purcell 2014). This task often requires two pivotal approaches: linkage ...

  5. Genomewide association study for seeding emergence and tiller ...

    Indian Academy of Sciences (India)

    A total of 31 loci were found to be associated with seeding emergence rate (SER) and tiller number in different growth stages. Loci distributed among 12 chromosomesaccounted for 5.35 to 11.33% of the observed phenotypic variation. With this information, 10 stable SNPs were identified for eventual development of cleaved ...

  6. Inverse association between dairy intake and hypertension: the Rotterdam Study

    NARCIS (Netherlands)

    Engberink, M.F.; Hendriksen, M.A.H.; Schouten, E.G.; Rooij, van F.J.A.; Hofman, A.; Witteman, J.C.; Geleijnse, J.M.

    2009-01-01

    Background: Little is known about the effect of different types of dairy food products on the development of hypertension. Objective: The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products. Design: We examined the

  7. Association studies of dormancy and cooking quality traits in direct ...

    Indian Academy of Sciences (India)

    Association analysis was applied to a panel of accessions of Assam rice (indica) using 98 SSR markers for dormancy-related traits and cooking quality. Analysis of population structure revealed 10 subgroups in the population. The mean r 2 and D ′ value for all intrachromosomal loci pairs was 0.24 and 0.51, respectively.

  8. Small bowel angiodysplasia and novel disease associations: a cohort study.

    LENUS (Irish Health Repository)

    Holleran, Grainne

    2013-04-01

    Gastrointestinal angiodysplasias recurrently bleed, accounting for 3-5% of obscure gastrointestinal bleeding. The advent of small bowel capsule endoscopy (SBCE) has led to an increased recognition of small bowel angiodysplasias (SBAs) but little is known about their etiology. Previous small cohorts and case reports suggest an equal gender incidence and associations with cardiovascular disease, renal impairment, and coagulopathies.

  9. A Retrospective Study of Factors associated with Newcastle Disease ...

    African Journals Online (AJOL)

    Newcastle disease outbreaks were significantly associated with the following factors namely: confinement of birds in all ecological zones except in lower midland 5 where most cases were reported without confinement; mode of disposal of infected birds, carcasses and poultry faecal matter; dry seasons in the dry zones just ...

  10. Immunohistochemical study of porcine lung lesions associated with Pasteurella multocida.

    Science.gov (United States)

    Pors, Susanne E; Hansen, Mette S; Bisgaard, Magne; Jensen, Henrik E; Iburg, Tine M

    2013-08-01

    Infectious bronchopneumonia is a widespread disease in modern commercial pig production and Pasteurella multocida is frequently associated with the lesions. To evaluate porcine lung lesions associated with P. multocida, populations of inflammatory cells were examined by immunohistochemistry in necrotic lung lesions from nine pigs and exudative lung lesions from eleven pigs. Lungs from five pigs served as controls. All cases were selected from naturally infected pigs using co-infection based criteria to make them as comparable as possible. The inflammatory cells demonstrated by immunohistochemistry were T-lymphocytes (CD3(+), CD4(+) and CD8(+) subsets), B-lymphocytes, neutrophils, macrophages, and IgA(+), IgM(+) and IgG(+) cells. The results showed that (1) a significant increase in all inflammatory cells was found in lesions associated with P. multocida, (2) necrotic lesions had a larger number of CD3(+) T-lymphocytes and IgA(+) cells, and (3) cases with exudative lesions had a more CD8(+) T-lymphocytes, B-lymphocytes, macrophages and neutrophils. No differences in the numbers of CD4(+) T-lymphocytes, IgG(+) and IgM(+) positive cells were found between necrotic and exudative cases. The results show that P. multocida significantly alters the inflammatory response in the lung and that lesions associated with P. multocida display diverse inflammatory responses according to their distinct morphological pattern. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Weinberg equilibrium and association study of insertion/deletion ...

    African Journals Online (AJOL)

    Mostafa Saadat

    2014-08-22

    Aug 22, 2014 ... [1]. The authors investigated whether insertion/deletion polymor- phism (dbSNP rs1799752) of the angiotensin converting enzyme (EC 3.4.15.1; ACE; OMIM: 106180) was associated with the risk of Alzheimer's disease in Egyptian patients. The authors reported that their findings support the hypothesis.

  12. Page 1 Spectroscopic Studies of the Associations of Heterocyclic ...

    Indian Academy of Sciences (India)

    appears in the region of 2950 cm.” The small values of e, of this band in solutions of 0-3 to 0-4 molar is due to the presence of smaller percentage of monomers at these concentrations. But with increasing dilution of the amines in chloroform, the intermolecular associations break up progressively and the hydrogen atoms of ...

  13. Gender & Education Association: A Case Study in Feminist Education?

    Science.gov (United States)

    David, Miriam E.

    2015-01-01

    This article focuses on feminist activist academics who were instrumental in creating the UK Gender & Education Association at the turn of the twenty-first century. Drawing on my own intellectual biography (David, M. E. 2003. "Personal and Political: Feminisms, Sociology and Family Lives" Stoke-on-Trent. Trentham Books.) linked to…

  14. Genomewide association study to detect QTL for twinning rate in ...

    Indian Academy of Sciences (India)

    Mohsen Gholizadeh, Ghodrat Rahimi-Mianji, Ardeshir Nejati-Javaremi, Dirk Jan De Koning and Elisabeth Jonas. J. Genet. 93, 489–493. Chromosome. 02468. − log. 10. (p. ) 1. 2. 3. 4 5 6 7. 9. 11 13 15 17 19. 22 25 27. Figure 1. Manhattan plot of the results from the genomewide association analysis for twinning during the ...

  15. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

    OpenAIRE

    Hensman Moss, Davina J; Pardinas, Antonio; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A

    2017-01-01

    Background\\ud \\ud Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.\\ud \\ud Methods\\ud \\ud We generated a progression score on the basis of principal ...

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

    Directory of Open Access Journals (Sweden)

    Binod Neupane

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

  17. Association Between Coronary Artery Disease Genetic Variants and Subclinical Atherosclerosis: An Association Study and Meta-analysis.

    Science.gov (United States)

    Zabalza, Michel; Subirana, Isaac; Lluis-Ganella, Carla; Sayols-Baixeras, Sergi; de Groot, Eric; Arnold, Roman; Cenarro, Ana; Ramos, Rafel; Marrugat, Jaume; Elosua, Roberto

    2015-10-01

    Recent studies have identified several genetic variants associated with coronary artery disease. Some of these genetic variants are not associated with classical cardiovascular risk factors and the mechanism of such associations is unclear. The aim of the study was to determine whether these genetic variants are related to subclinical atherosclerosis measured by carotid intima media thickness, carotid stiffness, and ankle brachial index. A cross-sectional study nested in the follow-up of the REGICOR cohort was undertaken. The study included 2667 individuals. Subclinical atherosclerosis measurements were performed with standardized methods. Nine genetic variants were genotyped to assess associations with subclinical atherosclerosis, individually and in a weighted genetic risk score. A systematic review and meta-analysis of previous studies that analyzed these associations was undertaken. Neither the selected genetic variants nor the genetic risk score were significantly associated with subclinical atherosclerosis. In the meta-analysis, the rs1746048 (CXCL12; n = 10581) risk allele was directly associated with carotid intima-media thickness (β = 0.008; 95% confidence interval, 0.001-0.015), whereas the rs6725887 (WDR12; n = 7801) risk allele was inversely associated with this thickness (β = -0.013; 95% confidence interval, -0.024 to -0.003). The analyzed genetic variants seem to mediate their association with coronary artery disease through different mechanisms. Our results generate the hypothesis that the CXCL12 variant appears to influence coronary artery disease risk through arterial remodeling and thickening, whereas the WDR12 risk variant could be related to higher plaque vulnerability. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  18. An association study between the norepinephrine transporter gene and depression

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette N; Jacobsen, Iben S; Grynderup, Matias B

    2013-01-01

    A2 for solute carrier 6 family member 2). The gene is responsible for the reuptake of norepinephrine and dopamine into presynaptic nerve terminals and the norepinephrine system appears to play an important role in depression. We therefore analyzed genetic variants within SLC6A2 for association......A potential approach for identification of candidate genes for depression is characterization of chromosomal rearrangements. Through analysis of a chromosome translocation in an individual with recurrent depression, we identified a potential candidate gene: the norepinephrine transporter (NET; SLC6...... with depression in 408 affected and 559 control individuals from Denmark. After quality control of the genotypes, 31 of 45 single nucleotide polymorphisms (SNPs) were left for analyses. One SNP showed a nominal association with depression but did not survive correction for multiple testing. The results from our...

  19. Update of recent studies of adenomyosis-associated dysmenorrhea

    Directory of Open Access Journals (Sweden)

    Caixia Jiang

    2016-11-01

    Full Text Available Adenomyosis is characterized by invasion of endometrial glands and stromal cells into the myometrium. It is a common gynecological disorder that usually occurs in women during their reproductive years. The primary clinical manifestations of adenomyosis are menorrhagia and progressive dysmenorrhea. The pathogenesis of adenomyosis-associated dysmenorrhea is complicated. However, it is predicted that oxytocin, inflammatory factors, and prostaglandin F2α are responsible for adenomyosis-associated dysmenorrhea via the induction of uterine smooth muscle contractions. Additionally, the pain conductivity of the pelvic viscera (internal organs involves both the sympathetic (T10–L1 and parasympathetic (S2–4 nervous systems located in the abdominal region. This article provides a review of the pathophysiology of dysmenorrhea in adenomyosis and the nociceptive afferent pathway of the pelvic splanchnic nerves.

  20. Porcine NAMPT gene: search for polymorphism, mapping and association studies.

    Science.gov (United States)

    Cepica, S; Bartenschlager, H; Ovilo, C; Zrůstová, J; Masopust, M; Fernández, A; López, A; Knoll, A; Rohrer, G A; Snelling, W M; Geldermann, H

    2010-12-01

    NAMPT encodes an enzyme catalysing the rate-limiting step in NAD biosynthesis. The extracellular form of the enzyme is known as adipokine visfatin. We detected SNP AM999341:g.669T>C (referred to as 669T>C) in intron 9 and SNP FN392209:g.358A>G (referred to as 358A>G) in the promoter of the gene. RH mapping linked the gene to microsatellite SW944. Linkage analysis placed the gene on the current USDA – USMARC linkage map at position 92 cM on SSC9. Association analyses were performed in a wild boar × Meishan F2 family (W × M), with 45 traits recorded (growth and fattening, fat deposition, muscling, meat quality, stress resistance and other traits), and in a commercial Landrace × Chinese-European (LCE) synthetic population with records for 15 traits (growth, fat deposition, muscling, intramuscular fat, meat colour and backfat fatty acid content). In the W × M, SNP 669T>C was associated with muscling, fat deposition, growth and fattening, meat quality and other traits and in the LCE with muscling, meat quality and backfat fatty acid composition. In the W × M, SNP 358A>G was associated with muscling, fat deposition, growth and other traits. After correction for multiple testing, the NAMPT haplotypes were associated in the W × M with, in descending order, muscling (q = 0.0056), growth (q = 0.0056), fat deposition (q = 0.0109), fat-to-meat ratio (q = 0.0135), cooling losses (q = 0.0568) and longissimus pHU (q = 0.0695). The SNPs are hypothesized to be in linkage disequilibrium with a causative mutation affecting energy metabolism as a whole rather than fat metabolism alone.

  1. Multiple Comparison Procedures for Neuroimaging Genomewide Association Studies

    OpenAIRE

    Hua, Wen-Yu; Nichols, Thomas E.; Ghosh, Debashis; Initiative, the Alzheimer's Disease Neuroimaging

    2014-01-01

    Recent research in neuroimaging has focused on assessing associations between genetic variants that are measured on a genomewide scale and brain imaging phenotypes. A large number of works in the area apply massively univariate analyses on a genomewide basis to find single nucleotide polymorphisms that influence brain structure. In this paper, we propose using various dimensionality reduction methods on both brain structural MRI scans and genomic data, motivated by the Alzheimer's Disease Neu...

  2. Impact of Semantic Relatedness on Associative Memory: An ERP Study

    Directory of Open Access Journals (Sweden)

    Pierre Desaunay

    2017-06-01

    Full Text Available Encoding and retrieval processes in memory for pairs of pictures are thought to be influenced by inter-item similarity and by features of individual items. Using Event-Related Potentials (ERP, we aimed to identify how these processes impact on both the early mid-frontal FN400 and the Late Positive Component (LPC potentials during associative retrieval of pictures. Twenty young adults undertook a sham task, using an incidental encoding of semantically related and unrelated pairs of drawings. At test, we conducted a recognition task in which participants were asked to identify target identical pairs of pictures, which could be semantically related or unrelated, among new and rearranged pairs. We observed semantic (related and unrelated pairs and condition effects (old, rearranged and new pairs on the early mid-frontal potential. First, a lower amplitude was shown for identical and rearranged semantically related pairs, which might reflect a retrieval process driven by semantic cues. Second, among semantically unrelated pairs, we found a larger negativity for identical pairs, compared to rearranged and new ones, suggesting additional retrieval processing that focuses on associative information. We also observed an LPC old/new effect with a mid-parietal and a right occipito-parietal topography for semantically related and unrelated old pairs, demonstrating a recollection phenomenon irrespective of the degree of association. These findings suggest that associative recognition using visual stimuli begins at early stages of retrieval, and differs according to the degree of semantic relatedness among items. However, either strategy may ultimately lead to recollection processes.

  3. Impact of Semantic Relatedness on Associative Memory: An ERP Study

    Science.gov (United States)

    Desaunay, Pierre; Clochon, Patrice; Doidy, Franck; Lambrechts, Anna; Bowler, Dermot M.; Gérardin, Priscille; Baleyte, Jean-Marc; Eustache, Francis; Guillery-Girard, Bérengère

    2017-01-01

    Encoding and retrieval processes in memory for pairs of pictures are thought to be influenced by inter-item similarity and by features of individual items. Using Event-Related Potentials (ERP), we aimed to identify how these processes impact on both the early mid-frontal FN400 and the Late Positive Component (LPC) potentials during associative retrieval of pictures. Twenty young adults undertook a sham task, using an incidental encoding of semantically related and unrelated pairs of drawings. At test, we conducted a recognition task in which participants were asked to identify target identical pairs of pictures, which could be semantically related or unrelated, among new and rearranged pairs. We observed semantic (related and unrelated pairs) and condition effects (old, rearranged and new pairs) on the early mid-frontal potential. First, a lower amplitude was shown for identical and rearranged semantically related pairs, which might reflect a retrieval process driven by semantic cues. Second, among semantically unrelated pairs, we found a larger negativity for identical pairs, compared to rearranged and new ones, suggesting additional retrieval processing that focuses on associative information. We also observed an LPC old/new effect with a mid-parietal and a right occipito-parietal topography for semantically related and unrelated old pairs, demonstrating a recollection phenomenon irrespective of the degree of association. These findings suggest that associative recognition using visual stimuli begins at early stages of retrieval, and differs according to the degree of semantic relatedness among items. However, either strategy may ultimately lead to recollection processes. PMID:28706479

  4. A Longitudinal Study of Association between Adiposity Markers and Intraocular Pressure: The Kangbuk Samsung Health Study.

    Directory of Open Access Journals (Sweden)

    Di Zhao

    Full Text Available Intraocular pressure (IOP reduction or stabilization is the only proven method for glaucoma management. Identifying risk factors for IOP is crucial to understand the pathophysiology of glaucoma.To examine the associations of change in body mass index (BMI, waist circumference, and percent fat mass with change in intraocular pressure (IOP in a large sample of Korean adults.Cohort study of 274,064 young and middle age Korean adults with normal fundoscopic findings who attended annual or biennial health exams from January 1, 2002 to Feb 28, 2010 (577,981 screening visits.BMI, waist circumference, and percent fat mass.At each visit, IOP was measured in both eyes with automated noncontact tonometers.In multivariable-adjusted models, the average increase in IOP (95% confidence intervals over time per interquartile increase in BMI (1.26 kg/m2, waist circumference (6.20 cm, and percent fat mass (3.40% were 0.18 mmHg (0.17 to 0.19, 0.27 mmHg (0.26 to 0.29, and 0.10 mmHg (0.09 to 0.11, respectively (all P < 0.001. The association was stronger in men compared to women (P < 0.001 and it was only slightly attenuated after including diabetes and hypertension as potential mediators in the model.Increases in adiposity were significantly associated with an increase in IOP in a large cohort of Korean adults attending health screening visits, an association that was stronger for central obesity. Further research is needed to understand better the underlying mechanisms of this association, and to establish the role of weight gain in increasing IOP and the risk of glaucoma and its complications.

  5. A refined study of FCRL genes from a genome-wide association study for Graves' disease.

    Directory of Open Access Journals (Sweden)

    Shuang-Xia Zhao

    Full Text Available To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves' disease (GD and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in CD19(+ B cells and CD8(+ T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level (P(combined = 2.27×10(-12 and 7.11×10(-13, respectively. Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs.

  6. A Longitudinal Study of Association between Adiposity Markers and Intraocular Pressure: The Kangbuk Samsung Health Study.

    Science.gov (United States)

    Zhao, Di; Kim, Myung Hun; Pastor-Barriuso, Roberto; Chang, Yoosoo; Ryu, Seungho; Zhang, Yiyi; Rampal, Sanjay; Shin, Hocheol; Kim, Joon Mo; Friedman, David S; Guallar, Eliseo; Cho, Juhee

    2016-01-01

    Intraocular pressure (IOP) reduction or stabilization is the only proven method for glaucoma management. Identifying risk factors for IOP is crucial to understand the pathophysiology of glaucoma. To examine the associations of change in body mass index (BMI), waist circumference, and percent fat mass with change in intraocular pressure (IOP) in a large sample of Korean adults. Cohort study of 274,064 young and middle age Korean adults with normal fundoscopic findings who attended annual or biennial health exams from January 1, 2002 to Feb 28, 2010 (577,981 screening visits). BMI, waist circumference, and percent fat mass. At each visit, IOP was measured in both eyes with automated noncontact tonometers. In multivariable-adjusted models, the average increase in IOP (95% confidence intervals) over time per interquartile increase in BMI (1.26 kg/m2), waist circumference (6.20 cm), and percent fat mass (3.40%) were 0.18 mmHg (0.17 to 0.19), 0.27 mmHg (0.26 to 0.29), and 0.10 mmHg (0.09 to 0.11), respectively (all P < 0.001). The association was stronger in men compared to women (P < 0.001) and it was only slightly attenuated after including diabetes and hypertension as potential mediators in the model. Increases in adiposity were significantly associated with an increase in IOP in a large cohort of Korean adults attending health screening visits, an association that was stronger for central obesity. Further research is needed to understand better the underlying mechanisms of this association, and to establish the role of weight gain in increasing IOP and the risk of glaucoma and its complications.

  7. Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.

    Science.gov (United States)

    Schwartz, T H; Rhiew, R; Isaacson, S R; Orazi, A; Bruce, J N

    2001-11-01

    Intracranial plasmacytomas are rare lesions that can arise from the calvarium, dura, or cranial base and exhibit a benign course unless associated with myeloma. Attention has recently been focused on the role of the cell adhesion molecules CD56 and CD31 in the pathogenesis of myeloma. No such information is available for intracranial plasmacytomas and myeloma-associated lesions. We investigated the relationship between CD56 and CD31 expression, intracranial location, and progression to myeloma for a series of nine intracranial plasmacytomas (three dural, one calvarial, and five cranial base lesions). These parameters were also correlated with proliferation indices, as assessed by MIB-1 immunostaining of the histological sections. A single pathologist (AO) performed immunohistochemical analyses and reviewed all slides. Intracranial plasmacytomas presented more commonly in female patients (89%). The three dural lesions were CD56- and CD31-negative and exhibited MIB-1 staining of less than 10%; no patient developed myeloma or recurrence. Of the five cranial base lesions, three were CD56-positive, none was CD31-positive, and two exhibited MIB-1 labeling of more than 45%, with plasmablastic morphological features. Compared with other intracranial plasmacytomas, five of five patients with cranial base lesions developed bone marrow biopsy-proven myeloma (P myeloma soon after diagnosis. Both of the two highly proliferative plasmablastic lesions recurred, one after gross total resection without radiotherapy and the other after a biopsy and 2000-cGy radiotherapy. Among intracranial plasmacytomas, cranial base location was the strongest predictor of the development of multiple myeloma. Expression of the cell adhesion molecules CD31 and CD56 was not predictive of outcome. Extramedullary dural-based lesions were CD56-negative and were not associated with myeloma. A high proliferation index and plasmablastic morphological features were predictive of a short time to recurrence

  8. Anonymizing patient genomic data for public sharing association studies.

    Science.gov (United States)

    Fernandez-Lozano, Carlos; Lopez-Campos, Guillermo; Seoane, Jose A; Lopez-Alonso, Victoria; Dorado, Julian; Martín-Sanchez, Fernando; Pazos, Alejandro

    2013-01-01

    The development of personalized medicine is tightly linked with the correct exploitation of molecular data, especially those associated with the genome sequence along with these use of genomic data there is an increasing demand to share these data for research purposes. Transition of clinical data to research is based in the anonymization of these data so the patient cannot be identified, the use of genomic data poses a great challenge because its nature of identifying data. In this work we have analyzed current methods for genome anonymization and propose a one way encryption method that may enable the process of genomic data sharing accessing only to certain regions of genomes for research purposes.

  9. A study on the mixed jaw lesions associated with teeth

    Energy Technology Data Exchange (ETDEWEB)

    Nah, Kyung Soo [Dept. of Dental Radiology, College of Dentistry, Pusan National University, Pusan (Korea, Republic of)

    2000-03-15

    1. Retrospectively evaluate the accuracy of tentative diagnosis or impression from the clinico-radiographic materials of jaw lesions which showed mixed lesions associated with teeth. 2. To observe the diagnostic importance of the calcified part of the lesions which appear as radiopaque areas. 14 cases of jaw lesions which showed mixed lesions associated with teeth were reviewed. These lesions were mostly diagnosed as adenomatoid odontogenic tumors (6 cases) or calcifying odontogenic cysts with (4 cases) or without odontomas (4 cases). The calcified elements of the lesions which demonstrated various sizes and patterns of radiopaque shadows resembled odontoid tissues in some cases but could not be defined in some other cases radiographically. The final histopathologic diagnosis confirmed adenomatoid odontogenic tumors in 4 of the 6 cases. The remaining 2 cases turned out to be odontoma and ameloblastic fibroodontoma. The 4 cases of calcifying odontogenic cysts with odontomas were correct in 3 cases but remaining 1 case was just odontoma. The 4 cases of calcifying odontogenic cysts were proved to be odontogenic keratocyst, calcified peripheral fibroma, unicystic ameloblastoma and squamous cell carcinoma. The diagnostic accuracy of the adenomatoid odontogenic tumors and calcifying odontogenic cysts were high when the lesions show typical appearance. The calcifications which show radiopaque areas could be odontomas or dystrophic calficifations or remnants of bone fragments from resorption.

  10. Immunohistochemical study of hepatic fibropoiesis associated with canine visceral leishmaniasis.

    Science.gov (United States)

    Madeira, Igor M V M; Pereira, Debora M O; Sousa, Aline A; Vilela, Cesar A; Amorim, Izabela F G; Caliari, Marcelo V; Souza, Carolina C; Tafuri, Wagner L

    2016-04-01

    Hepatic fibropoiesis has been confirmed in canine visceral leishmaniasis. In fibrotic disease, hepatic stellate cells (HSC) play an important role in fibropoiesis, undergoing activation by TGF-β to acquire characteristics of myofibroblasts. These cells show extensive capacity for proliferation, motility, contractility, collagen synthesis and extracellular matrix component synthesis. The aim of this work was to identify markers of HSC activation in 10 symptomatic and 10 asymptomatic dogs naturally infected with Leishmania (Leishmania) infantum. Eight uninfected dogs were used as controls. Alpha-actin (α-SMA), vimentin and cytokeratin were investigated by immunohistochemistry as HSC markers. The cytokine TGF-β in tissue was also evaluated by immunohistochemistry. All infected dogs showed higher numbers of reticular fibres than controls. Fibropoiesis found in infected dogs was always associated with the presence of parasites and chronic granulomatous hepatitis. Positive correlation was found among fibropoiesis, parasite tissue load and expression of α-SMA. There was no correlation between fibropoiesis, vimentin and cytokeratin markers. The expression of cytokine TGF-β was higher in infected dogs than in controls, but not significantly different between symptomatic and asymptomatic dogs. These results confirm previous work describing the intense hepatic fibropoiesis in dogs naturally infected with Leishmania infantum, but now associated them with overexpression of TGF-β, where α-SMA may be a superior marker for activated HSC cells in CVL. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  11. Study of methanogen communities associated with different rumen protozoal populations.

    Science.gov (United States)

    Belanche, Alejandro; de la Fuente, Gabriel; Newbold, Charles J

    2014-12-01

    Protozoa-associated methanogens (PAM) are considered one of the most active communities in the rumen methanogenesis. This experiment investigated whether methanogens are sequestrated within rumen protozoa, and structural differences between rumen free-living methanogens and PAM. Rumen protozoa were harvested from totally faunated sheep, and six protozoal fractions (plus free-living microorganisms) were generated by sequential filtration. Holotrich-monofaunated sheep were also used to investigate the holotrich-associated methanogens. Protozoal size determined the number of PAM as big protozoa had 1.7-3.3 times more methanogen DNA than smaller protozoa, but also more endosymbiotic bacteria (2.2- to 3.5-fold times). Thus, similar abundance of methanogens with respect to total bacteria were observed across all protozoal fractions and free-living microorganisms, suggesting that methanogens are not accumulated within rumen protozoa in a greater proportion to that observed in the rumen as a whole. All rumen methanogen communities had similar diversity (22.2 ± 3.4 TRFs). Free-living methanogens composed a conserved community (67% similarity within treatment) in the rumen with similar diversity but different structures than PAM (P methane mitigation strategies. © 2014 The Authors. FEMS Microbiology Ecology published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

  12. Study of outgoing longwave radiation anomalies associated with Haiti earthquake

    Directory of Open Access Journals (Sweden)

    P. Xiong

    2010-10-01

    Full Text Available The paper presents an analysis by using the methods of Eddy field calculation mean and wavelet maxima to detect seismic anomalies within the outgoing longwave radiation (OLR data based on time and space. The distinguishing feature of the method of Eddy field calculation mean is that we can calculate "the total sum of the difference value" of "the measured value" between adjacent points, which could highlight the singularity within data. The identified singularities are further validated by wavelet maxima, which using wavelet transformations as data mining tools by computing the maxima that can be used to identify obvious anomalies within OLR data. The two methods has been applied to carry out a comparative analysis of OLR data associated with the earthquake recently occurred in Haiti on 12 January 2010. Combining with the tectonic explanation of spatial and temporal continuity of the abnormal phenomena, the analyzed results have indicated a number of singularities associated with the possible seismic anomalies of the earthquake and from the comparative experiments and analyses by using the two methods, which follow the same time and space, we conclude that the singularities observed from 19 to 24 December 2009 could be the earthquake precursor of Haiti earthquake.

  13. Malnutrition is associated with poor rehabilitation outcome in elderly inpatients with hospital-associated deconditioning a prospective cohort study.

    Science.gov (United States)

    Wakabayashi, Hidetaka; Sashika, Hironobu

    2014-03-01

    To investigate the association between nutritional status and rehabilitation outcome in elderly inpatients with hospital-associated deconditioning. A prospective cohort study. One hundred sixty-nine consecutive elderly inpatients diagnosed with hospital-associated deconditioning. Nutritional status at referral was assessed by the Mini Nutritional Assessment Short Form at the University Medical Center. Body mass index, haemoglobin, albumin, total lymphocyte count, C-reactive protein, cause of malnutrition, and feeding route were also investigated. Primary outcome was Barthel Index score at discharge. A total of 148 patients (87.6%) were malnourished, and 21 were at risk for malnutrition. There were no patients with normal nutritional status. Malnourished patients had a lower Barthel Index score at discharge than those at risk for malnutrition. Chronic disease-related malnutrition, oral intake, and parenteral nutrition were associated with the Barthel Index score at discharge. There were significant correlations between the Barthel Index score at discharge and nutritional score, albumin, and total lymphocyte count. In multiple regression analysis, Mini Nutritional Assessment Short Form, albumin, and chronic disease-related malnutrition were significantly associated with the Barthel Index score at discharge. Most elderly inpatients with hospital-associated deconditioning are malnourished. Nutritional status, albumin, and chronic disease-related malnutrition are associated with poor rehabilitation outcome in hospital-associated deconditioning.

  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...... = 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)....

  15. Trajectories of Neighborhood Poverty and Associations With Subclinical Atherosclerosis and Associated Risk Factors: The Multi-Ethnic Study of Atherosclerosis

    OpenAIRE

    Murray, Emily T.; Diez Roux, Ana V.; Carnethon, Mercedes; Lutsey, Pamela L; Ni, Hanyu; O'Meara, Ellen S.

    2010-01-01

    The authors used data from the Multi-Ethnic Study of Atherosclerosis and latent trajectory class modeling to determine patterns of neighborhood poverty over 20 years (1980–2000 residential history questionnaires were geocoded and linked to US Census data). Using these patterns, the authors examined 1) whether trajectories of neighborhood poverty were associated with differences in the amount of subclinical atherosclerosis (common carotid intimal-media thickness) and 2) associated risk factors...

  16. Settlement Studies and Associated Problems in West Africa ...

    African Journals Online (AJOL)

    The paper examines settlement studies in the West African sub-tropics. It discusses the various traditions of settlement studies in West Africa with particular reference to Nigeria .The traditions are: socio-cultural and ecological traditions. The position of the paper is that though these traditions have been introduced and used ...

  17. Avidity Studies in Anisakis simplex-Associated Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Carmen Cuéllar

    2013-01-01

    Full Text Available Gastroallergic anisakiasis (GAA and Anisakis-sensitization-associated chronic urticaria (CU+ differ with respect to specific IgE levels. We hypothesised different immunoglobulin avidities in both entities as well as their dependence on TI and fish consumption. 16 patients with GAA and 17 patients with CU+ were included, and immunoglobulin levels were analysed by CAP (Phadia. IgE and IgG avidity indexes (AvIgE and AvIgG, resp. were also determined. IgG avidity was higher in GAA than in CU+ (P=0.035, whereas there was a tendency to lower IgE avidity in GAA (P=0.095. When analysing all patients, AvIgG was positively correlated with specific IgE, IgG, and IgG4 as well as total IgE (Rho between 0.66 and 0.71; P<0.002, but AvIgE was negatively correlated with specific IgE (Rho −0.57; P<0.001, specific IgG4 (Rho −0.38; P<0.05, and total IgE (Rho 0.66; P<0.001. In GAA, weekly fish consumption was positively associated with AvIgE (Rho 0.51; P=0.05. A multivariate regression showed that time interval was the main explaining factor for AvIgE in GAA. We could show a differential behaviour of immunoglobulin isotype avidities in both entities and their dependence on fish-eating habits as well as on the time elapsed to the last parasitic episode.

  18. Genome-wide Association Study of Obsessive-Compulsive Disorder

    Science.gov (United States)

    Stewart, S Evelyn; Yu, Dongmei; Scharf, Jeremiah M; Neale, Benjamin M; Fagerness, Jesen A; Mathews, Carol A; Arnold, Paul D; Evans, Patrick D; Gamazon, Eric R; Osiecki, Lisa; McGrath, Lauren; Haddad, Stephen; Crane, Jacquelyn; Hezel, Dianne; Illman, Cornelia; Mayerfeld, Catherine; Konkashbaev, Anuar; Liu, Chunyu; Pluzhnikov, Anna; Tikhomirov, Anna; Edlund, Christopher K; Rauch, Scott L; Moessner, Rainald; Falkai, Peter; Maier, Wolfgang; Ruhrmann, Stephan; Grabe, Hans-Jörgen; Lennertz, Leonard; Wagner, Michael; Bellodi, Laura; Cavallini, Maria Cristina; Richter, Margaret A; Cook, Edwin H; Kennedy, James L; Rosenberg, David; Stein, Dan J; Hemmings, Sian MJ; Lochner, Christine; Azzam, Amin; Chavira, Denise A; Fournier, Eduardo; Garrido, Helena; Sheppard, Brooke; Umaña, Paul; Murphy, Dennis L; Wendland, Jens R; Veenstra-VanderWeele, Jeremy; Denys, Damiaan; Blom, Rianne; Deforce, Dieter; Van Nieuwerburgh, Filip; Westenberg, Herman GM; Walitza, Susanne; Egberts, Karin; Renner, Tobias; Miguel, Euripedes Constantino; Cappi, Carolina; Hounie, Ana G; Conceição do Rosário, Maria; Sampaio, Aline S; Vallada, Homero; Nicolini, Humberto; Lanzagorta, Nuria; Camarena, Beatriz; Delorme, Richard; Leboyer, Marion; Pato, Carlos N; Pato, Michele T; Voyiaziakis, Emanuel; Heutink, Peter; Cath, Danielle C; Posthuma, Danielle; Smit, Jan H; Samuels, Jack; Bienvenu, O Joseph; Cullen, Bernadette; Fyer, Abby J; Grados, Marco A; Greenberg, Benjamin D; McCracken, James T; Riddle, Mark A; Wang, Ying; Coric, Vladimir; Leckman, James F; Bloch, Michael; Pittenger, Christopher; Eapen, Valsamma; Black, Donald W; Ophoff, Roel A; Strengman, Eric; Cusi, Daniele; Turiel, Maurizio; Frau, Francesca; Macciardi, Fabio; Gibbs, J Raphael; Cookson, Mark R; Singleton, Andrew; Hardy, John; Crenshaw, Andrew T; Parkin, Melissa A; Mirel, Daniel B; Conti, David V; Purcell, Shaun; Nestadt, Gerald; Hanna, Gregory L; Jenike, Michael A; Knowles, James A; Cox, Nancy; Pauls, David L

    2014-01-01

    Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1,465 cases, 5,557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9,657 X-chromosome SNPs. Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two p-values were located within DLGAP1 (p=2.49×10-6 and p=3.44×10-6), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a p-value=3.84 × 10-8. However, when trios were meta-analyzed with the combined case-control samples, the p-value for this variant was 3.62×10-5, losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation-QTLs (p<0.001) and frontal lobe eQTLs (p=0.001) was observed within the top-ranked SNPs (p<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD. PMID:22889921

  19. Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.

    Science.gov (United States)

    Cordell, Heather J; Töpf, Ana; Mamasoula, Chrysovalanto; Postma, Alex V; Bentham, Jamie; Zelenika, Diana; Heath, Simon; Blue, Gillian; Cosgrove, Catherine; Granados Riveron, Javier; Darlay, Rebecca; Soemedi, Rachel; Wilson, Ian J; Ayers, Kristin L; Rahman, Thahira J; Hall, Darroch; Mulder, Barbara J M; Zwinderman, Aelko H; van Engelen, Klaartje; Brook, J David; Setchfield, Kerry; Bu'Lock, Frances A; Thornborough, Chris; O'Sullivan, John; Stuart, A Graham; Parsons, Jonathan; Bhattacharya, Shoumo; Winlaw, David; Mital, Seema; Gewillig, Marc; Breckpot, Jeroen; Devriendt, Koen; Moorman, Antoon F M; Rauch, Anita; Lathrop, G Mark; Keavney, Bernard D; Goodship, Judith A

    2013-04-01

    We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10(-7)) and replicated convincingly (P = 3.9 × 10(-5)) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10(-11) in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10(-7)) and replicated convincingly (P = 1.2 × 10(-5)) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10(-11) in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF.

  20. Exploratory investigation of genetic associations with basal cell carcinoma risk: genome-wide association study in Jeju Island, Korea.

    Science.gov (United States)

    Yun, Byung Min; Song, Jung-Kook; Lee, Ji-Young

    2014-01-01

    Little is known about the genetic associations with Basal cell carcinoma (BCC) risk in non-Caucasian populations, in which BCC is rare, as in Korea. We here conducted a pilot genome-wide association study (GWAS) in 12 patients and 48 standard controls. A total of 263,511 SNPs were analyzed with the Illumina HumanOmni1 Quad v1.0 DNA Analysis BeadChip for cases and Korean HapMap 570K for controls. SNP-based analyses, based on the allele genetic model with adjustment for sex and age showed suggestive associations with BCC risk for 6 SNPs with a P-value (P associations were not statistically significant after Bonferroni correction: rs1040503, rs2216491, rs13407683, rs4751072, rs9891263, and rs1368474. In addition, results from gene-based analyses showed suggestive associations with BCC risk for 33 candidate genes with a P-value (P associations with BCC (P > 0.05), likely due to the smaller sample size. Although this was a small-scale negative study, to our knowledge, we have conducted the first GWAS for BCC risk in an Asian population. Further large studies in non-Caucasian populations are required to achieve statistical significance and confirm these findings.

  1. Genome-wide association study identifies the GLDC/IL33 locus associated with survival of osteosarcoma patients.

    Science.gov (United States)

    Koster, Roelof; Panagiotou, Orestis A; Wheeler, William A; Karlins, Eric; Gastier-Foster, Julie M; Caminada de Toledo, Silvia Regina; Petrilli, Antonio S; Flanagan, Adrienne M; Tirabosco, Roberto; Andrulis, Irene L; Wunder, Jay S; Gokgoz, Nalan; Patiño-Garcia, Ana; Lecanda, Fernando; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Thomas, David M; Ballinger, Mandy L; Gorlick, Richard; Barkauskas, Donald A; Spector, Logan G; Tucker, Margaret; Belynda, D Hicks; Yeager, Meredith; Hoover, Robert N; Wacholder, Sholom; Chanock, Stephen J; Savage, Sharon A; Mirabello, Lisa

    2017-12-06

    Survival rates for osteosarcoma, the most common primary bone cancer, have changed little over the past three decades and are particularly low for patients with metastatic disease. We conducted a multi-institutional genome-wide association study (GWAS) to identify germline genetic variants associated with overall survival in 632 patients with osteosarcoma, including 523 patients of European ancestry and 109 from Brazil. We conducted a time-to-event analysis and estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with and without adjustment for metastatic disease. The results were combined across the European and Brazilian case sets using a random-effects meta-analysis. The strongest association after meta-analysis was for rs3765555 at 9p24.1, which was inversely associated with overall survival (HR = 1.76; 95% CI 1.41-2.18, p = 4.84 × 10-7 ). After imputation across this region, the combined analysis identified two SNPs that reached genome-wide significance. The strongest single association was with rs55933544 (HR = 1.9; 95% CI 1.5-2.4; p = 1.3 × 10-8 ), which localizes to the GLDC gene, adjacent to the IL33 gene and was consistent across both the European and Brazilian case sets. Using publicly available data, the risk allele was associated with lower expression of IL33 and low expression of IL33 was associated with poor survival in an independent set of patients with osteosarcoma. In conclusion, we have identified the GLDC/IL33 locus on chromosome 9p24.1 as associated with overall survival in patients with osteosarcoma. Further studies are needed to confirm this association and shed light on the biological underpinnings of this susceptibility locus. © 2017 UICC.

  2. Occupation, Personality, and Accidents: An Exploratory Study of Aggregate Associations

    National Research Council Canada - National Science Library

    Vickers, Jr., Ross R; Hervig, Linda K

    2005-01-01

    Accident rates vary widely across U.S. Navy enlisted occupations. Incumbents' characteristics may affect rates, but the infrequency of accidents makes it hard to test this hypothesis by studying individuals...

  3. A Retrospective Study Of Cannabis Use-Associated ...

    African Journals Online (AJOL)

    African Journal of Drug and Alcohol Studies ... About 90% and 47% were diagnosed with psychotic disorders and dependence syndrome, respectively. ... with severe psychopathologies and constituted over 70% of demand for treatment.

  4. Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer.

    Science.gov (United States)

    Wang, Cheng; Qin, Na; Zhu, Meng; Chen, Minjian; Xie, Kaipeng; Cheng, Yang; Dai, Juncheng; Liu, Jia; Xia, Yankai; Ma, Hongxia; Jin, Guangfu; Amos, Christopher I; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing

    2017-10-26

    Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (ORmeta = 0.87, Pmeta = 1.76 × 10-15) and the effect was much stronger in females (Pinteraction = 6.00 × 10-4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (β = -0.57, P = 1.68 × 10-3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Structural Studies of Adeno-Associated Virus Serotype 8 Capsid Transitions Associated with Endosomal Trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Hyun-Joo; Gurda, Brittney L.; McKenna, Robert; Potter, Mark; Byrne, Barry; Salganik, Maxim; Muzyczka, Nicholas; Agbandje-McKenna, Mavis (Florida)

    2012-09-17

    The single-stranded DNA (ssDNA) parvoviruses enter host cells through receptor-mediated endocytosis, and infection depends on processing in the early to late endosome as well as in the lysosome prior to nuclear entry for replication. However, the mechanisms of capsid endosomal processing, including the effects of low pH, are poorly understood. To gain insight into the structural transitions required for this essential step in infection, the crystal structures of empty and green fluorescent protein (GFP) gene-packaged adeno-associated virus serotype 8 (AAV8) have been determined at pH values of 6.0, 5.5, and 4.0 and then at pH 7.5 after incubation at pH 4.0, mimicking the conditions encountered during endocytic trafficking. While the capsid viral protein (VP) topologies of all the structures were similar, significant amino acid side chain conformational rearrangements were observed on (i) the interior surface of the capsid under the icosahedral 3-fold axis near ordered nucleic acid density that was lost concomitant with the conformational change as pH was reduced and (ii) the exterior capsid surface close to the icosahedral 2-fold depression. The 3-fold change is consistent with DNA release from an ordering interaction on the inside surface of the capsid at low pH values and suggests transitions that likely trigger the capsid for genome uncoating. The surface change results in disruption of VP-VP interface interactions and a decrease in buried surface area between VP monomers. This disruption points to capsid destabilization which may (i) release VP1 amino acids for its phospholipase A2 function for endosomal escape and nuclear localization signals for nuclear targeting and (ii) trigger genome uncoating.

  6. Genome-wide association study of generalized anxiety symptoms in the Hispanic Community Health Study/Study of Latinos.

    Science.gov (United States)

    Dunn, Erin C; Sofer, Tamar; Gallo, Linda C; Gogarten, Stephanie M; Kerr, Kathleen F; Chen, Chia-Yen; Stein, Murray B; Ursano, Robert J; Guo, Xiuqing; Jia, Yucheng; Qi, Qibin; Rotter, Jerome I; Argos, Maria; Cai, Jianwen; Penedo, Frank J; Perreira, Krista; Wassertheil-Smoller, Sylvia; Smoller, Jordan W

    2017-03-01

    Although generalized anxiety disorder (GAD) is heritable and aggregates in families, no genomic loci associated with GAD have been reported. We aimed to discover potential loci by conducting a genome-wide analysis of GAD symptoms in a large, population-based sample of Hispanic/Latino adults. Data came from 12,282 participants (aged 18-74) in the Hispanic Community Health Study/Study of Latinos. Using a shortened Spielberger Trait Anxiety measure, we analyzed the following: (i) a GAD symptoms score restricted to the three items tapping diagnostic features of GAD as defined by DSM-V; and (ii) a total trait anxiety score based on summing responses to all ten items. We first calculated the heritability due to common variants (h2SNP ) and then conducted a genome-wide association study (GWAS) of GAD symptoms. Replication was attempted in three independent Hispanic cohorts (Multi-Ethnic Study of Atherosclerosis, Women's Health Initiative, Army STARRS). The GAD symptoms score showed evidence of modest heritability (7.2%; P = 0.03), while the total trait anxiety score did not (4.97%; P = 0.20). One genotyped SNP (rs78602344) intronic to thrombospondin 2 (THBS2) was nominally associated (P = 5.28 × 10-8 ) in the primary analysis adjusting for psychiatric medication use and significantly associated with the GAD symptoms score in the analysis excluding medication users (P = 4.18 × 10-8 ). However, meta-analysis of the replication samples did not support this association. Although we identified a genome-wide significant locus in this sample, we were unable to replicate this finding. Evidence for heritability was also only detected for GAD symptoms, and not the trait anxiety measure, suggesting differential genetic influences within the domain of trait anxiety. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. [Study on platelet-associated tissue factor and its significance].

    Science.gov (United States)

    Huang, Xi-lian; Chen, Fang-ping; Du, Jian-wei; Peng, Min-yuan; Fu, Bin; Xie, Qin-zhi; He, Shi-lin

    2005-09-01

    To explore whether normal platelet contains tissue factor (TF), and the significance of platelet-associated TF (PATF). Platelets were isolated by Sepharose 2B gel column. ELISA was used to detect the TF content in the lysates of washed platelets. Procoagulant activity of PATF was measured by one stage clotting time assay. The mRNA of TF was detected by reverse transcription polymerase chain reaction (RT-PCR). A certain amount of TF antigen (16.37 +/- 6.39) ng/L was detected in the washed-platelet lysates. Upon activation by collagen, platelets released TF and caused a marked increase in TF level in plasma (P collagen increased significantly, which could be blocked by TF McAb and poor VII plasma. TF mRNA could not be detected in washed platelets. TF content in platelets from patients with coronary heart disease was significantly higher than that from normal controls (P < 0.05). Resting platelets from the patients showed a higher procoagulant activity, which could be inhibited by TF McAb. Platelets contain TF and the latter released by activated platelet was functionally active. Platelet itself might not synthesize TF. Protein content and procoagulant activity of PATF in patients with coronary heart disease were higher than that in controls. All these indicate that platelet may be involved in coagulation and thrombosis by releasing TF.

  8. Serologic Study of Pig-Associated Viral Zoonoses in Laos

    Science.gov (United States)

    Conlan, James V.; Vongxay, Khamphouth; Jarman, Richard G.; Gibbons, Robert V.; Lunt, Ross A.; Fenwick, Stanley; Thompson, R. C. Andrew; Blacksell, Stuart D.

    2012-01-01

    We conducted a serologic survey of four high-priority pig-associated viral zoonoses, Japanese encephalitis virus (JEV), hepatitis E virus (HEV), Nipah virus (NiV), and swine influenza virus (SIV), in Laos. We collected blood from pigs at slaughter during May 2008–January 2009 in four northern provinces. Japanese encephalitis virus hemagglutination inhibition seroprevalence was 74.7% (95% confidence interval [CI] = 71.5–77.9%), JEV IgM seroprevalence was 2.3% (95% CI = 1.2–3.2%), and HEV seroprevalence was 21.1% (95% CI = 18.1–24.0%). Antibodies to SIV were detected in 1.8% (95% CI = 0.8–2.8%) of pigs by screening enzyme-linked immunosorbent assay, and only subtype H3N2 was detected by hemagglutination inhibition in two animals with an inconclusive enzyme-linked immunosorbent assay result. No NiV antibody–positive pigs were detected. Our evidence indicates that peak JEV and HEV transmission coincides with the start of the monsoonal wet season and poses the greatest risk for human infection. PMID:22665622

  9. Weather Features Associated with Aircraft Icing Conditions: A Case Study

    Directory of Open Access Journals (Sweden)

    Sergio Fernández-González

    2014-01-01

    Full Text Available In the context of aviation weather hazards, the study of aircraft icing is very important because of several accidents attributed to it over recent decades. On February 1, 2012, an unusual meteorological situation caused severe icing of a C-212-200, an aircraft used during winter 2011-2012 to study winter cloud systems in the Guadarrama Mountains of the central Iberian Peninsula. Observations in this case were from a MP-3000A microwave radiometric profiler, which acquired atmospheric temperature and humidity profiles continuously every 2.5 minutes. A Cloud Aerosol and Precipitation Spectrometer (CAPS was also used to study cloud hydrometeors. Finally, ice nuclei concentration was measured in an isothermal cloud chamber, with the goal of calculating concentrations in the study area. Synoptic and mesoscale meteorological conditions were analysed using the Weather Research and Forecasting (WRF model. It was demonstrated that topography influenced generation of a mesolow and gravity waves on the lee side of the orographic barrier, in the region where the aircraft experienced icing. Other factors such as moisture, wind direction, temperature, atmospheric stability, and wind shear were decisive in the appearance of icing. This study indicates that icing conditions may arise locally, even when the synoptic situation does not indicate any risk.

  10. Weather features associated with aircraft icing conditions: a case study.

    Science.gov (United States)

    Fernández-González, Sergio; Sánchez, José Luis; Gascón, Estíbaliz; López, Laura; García-Ortega, Eduardo; Merino, Andrés

    2014-01-01

    In the context of aviation weather hazards, the study of aircraft icing is very important because of several accidents attributed to it over recent decades. On February 1, 2012, an unusual meteorological situation caused severe icing of a C-212-200, an aircraft used during winter 2011-2012 to study winter cloud systems in the Guadarrama Mountains of the central Iberian Peninsula. Observations in this case were from a MP-3000A microwave radiometric profiler, which acquired atmospheric temperature and humidity profiles continuously every 2.5 minutes. A Cloud Aerosol and Precipitation Spectrometer (CAPS) was also used to study cloud hydrometeors. Finally, ice nuclei concentration was measured in an isothermal cloud chamber, with the goal of calculating concentrations in the study area. Synoptic and mesoscale meteorological conditions were analysed using the Weather Research and Forecasting (WRF) model. It was demonstrated that topography influenced generation of a mesolow and gravity waves on the lee side of the orographic barrier, in the region where the aircraft experienced icing. Other factors such as moisture, wind direction, temperature, atmospheric stability, and wind shear were decisive in the appearance of icing. This study indicates that icing conditions may arise locally, even when the synoptic situation does not indicate any risk.

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

    Science.gov (United States)

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

    2017-01-01

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

  12. CCNA Cisco Certified Network Associate Deluxe Study Guide

    CERN Document Server

    Lammle, Todd

    2011-01-01

    Deluxe Edition of Best-Selling CCNA Study GuideThis comprehensive, enhanced version of the Sybex CCNA Study Guide provides certification candidates with the additional tools they need to prepare for this popular exam. With additional bonus exams and flashcards, as well as the exclusive CCNA Virtual Lab, Platinum Edition, this comprehensive guide has been completely updated to reflect the latest CCNA 640-802 exam. Written by Cisco Authority Todd Lammle, whose straightforward style provides lively examples, hands-on and written labs, easy-to-understand analogies, and real-world scenarios that wi

  13. A Study of Musculoskeletal Discomforts and Associated Risks ...

    African Journals Online (AJOL)

    The most popularly used percussion instruments in Indian classical music are Tabla. Therefore, the present study was conducted to find the most affected areas of discomfort and to identify the major risk factors contributing to playing related musculoskeletal discomforts among Indian Tabla players. Eighty-four professional ...

  14. In Vitro Antibiotic Susceptibility Studies Of Bacteria Associated With ...

    African Journals Online (AJOL)

    While single-agent therapy with fluoroquinolones for vision-threatening bacterial keratitis is not advisable, combination therapy with fluoroquinolones and erythromycin offers a reasonable alternative for the treatment of bacterial keratitis. Also, the isolation of Escherichia coli shows that further study is required to determine ...

  15. Geochemical study of volcanic and associated granitic rocks from ...

    Indian Academy of Sciences (India)

    Geochemical studies and modelling show that both volcanic and granitic magmas from the western part of the Johor National Park, Endau Rompin are different and probably have different sources. The geo- chemical plot suggests that both dacite/rhyolite and andesite probably have a common origin as in many.

  16. Study on the association between Maternal Malaria Infection and ...

    African Journals Online (AJOL)

    In a descriptive study in ABSUTH (Abia State University Teaching Hospital), Aba, a total of 317 expectant mothers were sampled randomly during the first and second stage of labour for the presence of malaria parasites. In the peripheral blood films and maternal anaemia. The mean haemoglobin concentration for mothers ...

  17. Study of polypharmacy and associated problems among elderly ...

    African Journals Online (AJOL)

    Information pertaining to the age, sex, religion, monthly income, education level, any previous illnesses, or any chronic diseases, any drug treatment, adherence to the treatment, and self medication or non-allopathic treatment was collected. The study included 310 elderly patients, among which 51.9% were males and ...

  18. HMGB1 in ANCA-associated vasculitis: A longitudinal study

    NARCIS (Netherlands)

    Silva De Souza, A.W.; Westra, J.; Bijzet, J.; Limburg, P.C.; Bijl, M.; Stegeman, C.A.; Kallenberg, C.G.M.

    2013-01-01

    Introduction.- Extra-cellular high mobility group box 1 (HMGB1) acts as an alarmin and has been shown to be a biomarker of disease activity in systemic lupus erythematosus (SLE). This study aims to assess anti- HMGB1 antibodies and HMGB1 levels as biomarkers for disease activity and predictors of

  19. Insulin association in neutral solutions studied by light scattering

    DEFF Research Database (Denmark)

    Hvidt, S.

    1991-01-01

    is monomeric over the studied concentration range. Weight average molecular weights between those of a monomer and a hexamer were found for both zinc-free and 2Zn insulins. Zinc stabilizes the hexamer, and the dimer-hexamer equilibrium constant is approx. 400-times higher in the presence of zinc than in its...

  20. Biochemical studies on changes associated with enzymes of ...

    African Journals Online (AJOL)

    SERVER

    2007-08-20

    Aug 20, 2007 ... Even at moribund stage, the glycolytic pathway was not affected, as evident from the normal activity of aldolase observed in the present study. Key words: WSSV, P. monodon, glucose, gluconeogenic enzymes, glycolytic enzymes. INTRODUCTION. The diseases of cultured penaeid shrimp include infec-.

  1. A comparative study of the socioeconomic factors associated with ...

    African Journals Online (AJOL)

    Background: Childhood sexual abuse (CSA) is a problem of considerable proportion in Africa where up to one-third of adolescent girls report their first sexual experience as being forced. The impact of child hood sexual abuse resonates in all areas of health. The aim of this study was to describe the prevalence of childhood ...

  2. A case study of possible health hazards associated with poultry ...

    African Journals Online (AJOL)

    This study on layer and broiler houses is expected to give basic information on the nature of microbes, their occurrence, health hazard they could constitute and the possibilities for disease control measures. Modern husbandry practices, state or local concentration of the industry, high stocking densities, uniform age ...

  3. A descriptive study of biological and psychosocial factors associated ...

    African Journals Online (AJOL)

    2017-08-31

    Aug 31, 2017 ... fast-food intake, breakfast skipping and not eating meals together with the family have a positive relationship with obesity.11. A US study by Bradford has ... Recent reviews have indicated the importance of parental involvement and parental monitoring of child health behaviours in preventing and treating ...

  4. Risk Factors Associated with Outcome in Liver Retransplantation : Multicentric Study

    NARCIS (Netherlands)

    Mattos, Rogerio O.; Linhares, Marcelo M.; Matos, Delcio; Adam, Rene; Bismuth, Henri; Castaing, Denis; Konietzko, Achim; Lerut, Jan; Porte, Robert J.; Neville, Jamieson; Azoulay, Daniel

    2015-01-01

    Background/Aims: To externally validate the predictive mathematical model of survival designed by Linhares et al. (2006). Methodology: This retrospective study was conducted on 217 individuals submitted to liver retransplantation from January 2000 to December 2008 in four European centers. The

  5. Recent advances in human gene-longevity association studies

    DEFF Research Database (Denmark)

    De Benedictis, G; Tan, Q; Jeune, B

    2001-01-01

    % of the variation in life span is genetically determined. Taking advantage of recent developments in molecular biology, researchers are now searching for candidate genes that might have an influence on life span. The data on unrelated individuals emerging from an ever-increasing number of centenarian studies makes...

  6. Geochemical study of volcanic and associated granitic rocks from ...

    Indian Academy of Sciences (India)

    Geochemical studies and modelling show that both volcanic and granitic magmas from the western part of the Johor National Park, Endau Rompin are different and probably have different sources. The geochemical plot suggests that both dacite/rhyolite and andesite probably have a common origin as in many of the ...

  7. A Bayesian multilocus association method: allowing for higher-order interaction in association studies

    DEFF Research Database (Denmark)

    Albrechtsen, Anders; Castella, Sofie; Andersen, Gitte

    2007-01-01

    For most common diseases with heritable components, not a single or a few single-nucleotide polymorphisms (SNPs) explain most of the variance for these disorders. Instead, much of the variance may be caused by interactions (epistasis) among multiple SNPs or interactions with environmental...... a Danish population-based cohort, multiple interactions are identified that severely affect serum triglyceride levels in the study individuals. The method is designed for quantitative traits but can also be applied on qualitative traits. It is computationally feasible even for a large number of possible...... interactions and differs fundamentally from most previous approaches by entertaining nonlinear interactions and by directly addressing the multiple-testing problem....

  8. Outcomes of Global Education: External and Internal Change Associated with Study Abroad

    Science.gov (United States)

    Miller-Perrin, Cindy; Thompson, Don

    2014-01-01

    This chapter provides an overview of external and internal changes associated with collegiate study abroad experiences. A brief review of the research literature is included along with recent research that sheds light on potential mechanisms associated with study abroad-related change. Recommendations for enhancing outcomes associated with study…

  9. Genome-wide association study of facial morphology reveals novel associations with FREM1 and PARK2.

    Science.gov (United States)

    Lee, Myoung Keun; Shaffer, John R; Leslie, Elizabeth J; Orlova, Ekaterina; Carlson, Jenna C; Feingold, Eleanor; Marazita, Mary L; Weinberg, Seth M

    2017-01-01

    Several studies have now shown evidence of association between common genetic variants and quantitative facial traits in humans. The reported associations generally involve simple univariate measures and likely represent only a small fraction of the genetic loci influencing facial morphology. In this study, we applied factor analysis to a set of 276 facial linear distances derived from 3D facial surface images of 2187 unrelated individuals of European ancestry. We retained 23 facial factors, which we then tested for genetic associations using a genome-wide panel of 10,677,593 single nucleotide polymorphisms (SNPs). In total, we identified genome-wide significant (p associations in three regions, including two that are novel: one involving measures of midface height at 6q26 within an intron of PARK2 (lead SNP rs9456748; p = 4.99 × 10-8) and another involving measures of central upper lip height at 9p22 within FREM1 (lead SNP rs72713618; p = 2.02 × 10-8). In both cases, the genetic association was stronger with the composite facial factor phenotype than with any of the individual linear distances that comprise those factors. While the biological role of PARK2 in the craniofacial complex is currently unclear, there is evidence from both mouse models and Mendelian syndromes that FREM1 may influence facial variation. These results highlight the potential value of data-driven multivariate phenotyping for genetic studies of human facial morphology.

  10. Studies of the W / Z Production Associated with Direct Photons

    Energy Technology Data Exchange (ETDEWEB)

    Brozovic, Marina [Duke Univ., Durham, NC (United States)

    2002-08-01

    We present an analysis of W/Z +γ events produced in p$/bar{p}$ collisions at the Fermilab Tevatron, with √s = 1.8 TeV. Our primary research interest is W/Z +γ production with W/Z bosons decaying hadronically, although we also study the properties of W/Z +γ production with the bosons decaying leptonically.

  11. Why Do We Test Multiple Traits in Genetic Association Studies?

    OpenAIRE

    Zhu, Wensheng; Zhang, Heping

    2009-01-01

    In studies of complex disorders such as nicotine dependence, it is common that researchers assess multiple variables related to a disorder as well as other disorders that are potentially correlated with the primary disorder of interest. In this work, we refer to those variables and disorders broadly as multiple traits. The multiple traits may or may not have a common causal genetic variant. Intuitively, it may be more powerful to accommodate multiple traits in genetic traits, but the analysis...

  12. Comparison of different cell type correction methods for genome-scale epigenetics studies.

    Science.gov (United States)

    Kaushal, Akhilesh; Zhang, Hongmei; Karmaus, Wilfried J J; Ray, Meredith; Torres, Mylin A; Smith, Alicia K; Wang, Shu-Li

    2017-04-14

    Whole blood is frequently utilized in genome-wide association studies of DNA methylation patterns in relation to environmental exposures or clinical outcomes. These associations can be confounded by cellular heterogeneity. Algorithms have been developed to measure or adjust for this heterogeneity, and some have been compared in the literature. However, with new methods available, it is unknown whether the findings will be consistent, if not which method(s) perform better. Methods: We compared eight cell-type correction methods including the method in the minfi R package, the method by Houseman et al., the Removing unwanted variation (RUV) approach, the methods in FaST-LMM-EWASher, ReFACTor, RefFreeEWAS, and RefFreeCellMix R programs, along with one approach utilizing surrogate variables (SVAs). We first evaluated the association of DNA methylation at each CpG across the whole genome with prenatal arsenic exposure levels and with cancer status, adjusted for estimated cell-type information obtained from different methods. We then compared CpGs showing statistical significance from different approaches. For the methods implemented in minfi and proposed by Houseman et al., we utilized homogeneous data with composition of some blood cells available and compared them with the estimated cell compositions. Finally, for methods not explicitly estimating cell compositions, we evaluated their performance using simulated DNA methylation data with a set of latent variables representing "cell types". Results from the SVA-based method overall showed the highest agreement with all other methods except for FaST-LMM-EWASher. Using homogeneous data, minfi provided better estimations on cell types compared to the originally proposed method by Houseman et al. Further simulation studies on methods free of reference data revealed that SVA provided good sensitivities and specificities, RefFreeCellMix in general produced high sensitivities but specificities tended to be low when

  13. Long sleep duration is associated with serum cholesterol in the elderly: The rotterdam study

    NARCIS (Netherlands)

    J.F. van den Berg (Julia); H.M. Miedema (Henk); J.H.M. Tulen (Joke); A.K. Neven (Arie); A. Hofman (Albert); J.C.M. Witteman (Jacqueline); H.W. Tiemeier (Henning)

    2008-01-01

    textabstractObjective: Epidemiological studies have repeatedly found increased mortality associated with both habitual short and long sleep duration. The mechanisms behind these associations are unclear. We investigated whether objectively measured sleep duration, time in bed, and sleep

  14. A mixed model reduces spurious genetic associations produced by population stratification in genome-wide association studies.

    Science.gov (United States)

    Shin, Jimin; Lee, Chaeyoung

    2015-04-01

    Population stratification can produce spurious genetic associations in genome-wide association studies (GWASs). Mixed model methodology has been regarded useful for correcting population stratification. This study explored statistical power and false discovery rate (FDR) with the data simulated for dichotomous traits. Empirical FDRs and powers were estimated using fixed models with and without genomic control and using mixed models with and without reflecting loci linked to the candidate marker in genetic relationships. Population stratification with admixture degree ranged from 1% to 10% resulted in inflated FDRs from the fixed model analysis without genomic control and decreased power from the fixed model analysis with genomic control (Ppopulation stratification could not change FDR and power estimates from the mixed model analyses (P>0.05). We suggest that the mixed model methodology was useful to reduce spurious genetic associations produced by population stratification in GWAS, even with a high degree of admixture (10%). Copyright © 2015 Elsevier Inc. All rights reserved.

  15. A statistical perspective on association studies of psychiatric disorders

    DEFF Research Database (Denmark)

    Foldager, Leslie

    2014-01-01

    Gene-gene (GxG) and gene-environment (GxE) interactions likely play an important role in the aetiology of complex diseases like psychiatric disorders. Thus, we aim at investigating methodological aspects of and apply methods from statistical genetics taking interactions into account. In addition we...... genes and maternal infection by virus. Paper 3 presents the initial steps (mainly data construction) of an ongoing simulation study aiming at guiding decisions by comparing methods for GxE interaction analysis including both traditional two-step logistic regression, exhaustive searches using efficient...

  16. 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

  17. Genetic Studies on Diabetic Microvascular Complications: Focusing on Genome-Wide Association Studies

    Directory of Open Access Journals (Sweden)

    Soo Heon Kwak

    2015-06-01

    Full Text Available Diabetes is a common metabolic disorder with a worldwide prevalence of 8.3% and is the leading cause of visual loss, end-stage renal disease and amputation. Recently, genome-wide association studies (GWASs have identified genetic risk factors for diabetic microvascular complications of retinopathy, nephropathy, and neuropathy. We summarized the recent findings of GWASs on diabetic microvascular complications and highlighted the challenges and our opinion on future directives. Five GWASs were conducted on diabetic retinopathy, nine on nephropathy, and one on neuropathic pain. The majority of recent GWASs were underpowered and heterogeneous in terms of study design, inclusion criteria and phenotype definition. Therefore, few reached the genome-wide significance threshold and the findings were inconsistent across the studies. Recent GWASs provided novel information on genetic risk factors and the possible pathophysiology of diabetic microvascular complications. However, further collaborative efforts to standardize phenotype definition and increase sample size are necessary for successful genetic studies on diabetic microvascular complications.

  18. Genome-wide Association Study and Admixture Mapping Reveal New Loci Associated with Total IgE Levels in Latinos

    Science.gov (United States)

    Pino-Yanes, Maria; Gignoux, Christopher R.; Galanter, Joshua M.; Levin, Albert M.; Campbell, Catarina D.; Eng, Celeste; Huntsman, Scott; Nishimura, Katherine K.; Gourraud, Pierre-Antoine; Mohajeri, Kiana; O'Roak, Brian J.; Hu, Donglei; Mathias, Rasika A.; Nguyen, Elizabeth A.; Roth, Lindsey A.; Padhukasahasram, Badri; Moreno-Estrada, Andres; Sandoval, Karla; Winkler, Cheryl A.; Lurmann, Fred; Davis, Adam; Farber, Harold J.; Meade, Kelley; Avila, Pedro C.; Serebrisky, Denise; Chapela, Rocio; Ford, Jean G.; Lenoir, Michael A.; Thyne, Shannon M.; Brigino-Buenaventura, Emerita; Borrell, Luisa N.; Rodriguez-Cintron, William; Sen, Saunak; Kumar, Rajesh; Rodriguez-Santana, Jose R.; Bustamante, Carlos D.; Martinez, Fernando D.; Raby, Benjamin A.; Weiss, Scott T.; Nicolae, Dan L.; Ober, Carole; Meyers, Deborah A.; Bleecker, Eugene R.; Mack, Steven J.; Hernandez, Ryan D.; Eichler, Evan E.; Barnes, Kathleen C.; Williams, L. Keoki; Torgerson, Dara G.; Burchard, Esteban G.

    2014-01-01

    Background Immunoglobulin E (IgE) is a key mediator of allergic inflammation and is frequently elevated in allergic disorders. Objective To identify genetic variants associated with IgE levels in Latinos. Methods We performed a genome-wide association study (GWAS) and admixture mapping of total IgE levels in 3,334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1,564 European Americans, and 3,187 African Americans from independent studies. Results We confirmed associations of six genes identified by previous GWAS and identified a novel genome-wide significant association of a polymorphism in ZNF365 with total IgE (rs200076616, p=2.3x10−8). We next identified four admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) where local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower levels of IgE (p=4.95x10−8). All but 22q13.1 were replicated in an independent sample of Latinos, and two of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified six genome-wide significant single nucleotide polymorphisms in Latinos, two of which replicated in European Americans. Another SNP was peak-wide significant within 14q23.2 in African Americans (rs1741099, p=3.7x10−6), and replicated in non-African American samples (p=0.011). Conclusion We confirmed genetic associations at six genes, and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse, multi-ethnic populations to uncover novel loci associated with total IgE levels. PMID:25488688

  19. Factors Associated with Involvement in Bullying: A Study in Nicaragua

    Directory of Open Access Journals (Sweden)

    Eva M. Romera

    2011-07-01

    Full Text Available School bullying is one of the main problems affecting the quality of peer relationships in schools and in general the coexistence. At European level, there are scientific findings that indicate its nature, characteristics and factors related to its involvement. However, in poor and developing countries, where the problem is more serious, there is a high degree of awareness on this matter. The present study aimed to identify what factors may be influencing the occurrence of bullying in a representative sample of primary schools in the Nicaraguan capital. For this propose, 3042 students from Managua and its metropolitan area were explored with instruments comparable to those used in Europe. A multinomial logistic regression analysis indicated that being a boy, to show antisocial behaviors and attitudes and contact with drugs were the three factors most related with the role of aggressor, as well as negative relationships had a significant influence on involvement in this phenomenon, either as a victim, aggressor or victimized aggressor. Results are discussed in relation to the profiles of aggressor and victim of bullying in international studies focusing on differences in developed countries.

  20. Genetic association studies: discovery of the genetic basis of renal disease

    NARCIS (Netherlands)

    Verduijn, Marion; Jager, Kitty J.; Zoccali, Carmine; Dekker, Friedo W.

    2011-01-01

    Genetic association studies are a means to investigate the causal role of genes in diseases in order to unravel pathways involved in the etiology of disease. There are two types of genetic association studies: hypothesis-driven studies, i.e. candidate gene studies, targeting genes with a known or

  1. Dietary Patterns are Associated with Helicobacter Pylori Infection in Chinese Adults: A Cross-Sectional Study

    OpenAIRE

    Yang Xia; Ge Meng; Qing Zhang; Li Liu; Hongmei Wu; Hongbin Shi; Xue Bao; Qian Su; Yeqing Gu; Liyun Fang; Fei Yu; Huijun Yang; Bin Yu; Shaomei Sun; Xing Wang

    2016-01-01

    Previous studies indicated that food consumption was associated with Helicobacter pylori infection, but no study has yet investigated the association between Helicobacter pylori infection and dietary patterns. The aim of this study was to evaluate the associations between Helicobacter pylori infection and dietary patterns in Tianjin, China. The final cross-sectional study population comprised 10407 participants. Dietary consumption of participants was assessed via food frequency questionnaire...

  2. Is grand-parental smoking associated with adolescent obesity? A three-generational study

    OpenAIRE

    Dougan, M M; Field, A. E.; Rich-Edwards, Janet Wilson; Hankinson, Susan Elizabeth; Glynn, Robert James; Willett, Walter C.; Michels, Karin B.

    2015-01-01

    Background/Objectives: Data from previous studies consistently suggest that maternal smoking is positively associated with obesity later in life. Whether this association persists across generations is unknown. We examined whether grand-parental smoking was positively associated with overweight status in adolescence. Subject/Methods: Participants were grandmother-mother-child triads in the Nurses’ Health Study II (NHS II), the Nurses Mothers’ Cohort Study, and the Growing up Today Study (GUTS...

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

    NARCIS (Netherlands)

    Wang, Z.; McGlynn, K.A.; Rajpert- de Meyts, E.; Bishop, D.T.; Chung, C.C.; Dalgaard, M.D.; Greene, M.H.; Gupta, R; Grotmol, T.; Haugen, T.B.; Karlsson, R.; Litchfield, K.; Mitra, N.; Nielsen, K.; Pyle, L.C.; Schwartz, S.M.; Thorsson, V.; Vardhanabhuti, S.; Wiklund, F.; Turnbull, C.; Chanock, S.J.; Kanetsky, P.A.; Nathanson, K.L.; Kiemeney, B.; Skotheim, R.I.; Zheng, T.

    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, the first

  4. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hansel, Nadia N.; Pare, Peter D.; Rafaels, Nicholas; Sin, Don D.; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W. Mark; Pascoe, Chris D.; Arsenault, Bryna A.; Postma, Dirkje S.; Boezen, Marieke H.; Bosse, Yohan; van den Berge, Maarten; Hiemstra, Pieter S.; Cho, Michael H.; Litonjua, Augusto A.; Sparrow, David; Ober, Carole; Wise, Robert A.; Connett, John; Neptune, Enid R.; Beaty, Terri H.; Ruczinski, Ingo; Mathias, Rasika A.; Barnes, Kathleen C.

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina

  5. Associations of Breast Cancer Risk Factors With Tumor Subtypes : A Pooled Analysis From the Breast Cancer Association Consortium Studies

    NARCIS (Netherlands)

    Yang, Xiaohong R.; Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J.; Van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O'Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M. S.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Doerk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Rodriguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collee, Margriet; Wang-Gohrke, Shan; Pylkaes, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Paeivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Orsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Borge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; Mckay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P. E. A.; Tollenaar, R. A. E. M.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients

  6. 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, the fi...

  7. Candidate pathway-based genome-wide association studies identify novel associations of genomic variants in the complement system associated with coronary artery disease.

    Science.gov (United States)

    Xu, Chengqi; Yang, Qin; Xiong, Hongbo; Wang, Longfei; Cai, Jianping; Wang, Fan; Li, Sisi; Chen, Jing; Wang, Chuchu; Wang, Dan; Xiong, Xin; Wang, Pengyun; Zhao, Yuanyuan; Wang, Xiaojing; Huang, Yufeng; Chen, Shanshan; Yin, Dan; Li, Xiuchun; Liu, Ying; Liu, Jinqiu; Wang, Jingjing; Li, Hui; Ke, Tie; Ren, Xiang; Wu, Yanxia; Wu, Gang; Wan, Jing; Zhang, Rongfeng; Wu, Tangchun; Wang, Junhan; Xia, Yunlong; Yang, Yanzong; Cheng, Xiang; Liao, Yuhua; Chen, Qiuyun; Zhou, Yanhong; He, Qing; Tu, Xin; Wang, Qing K

    2014-12-01

    Genomic variants identified by genome-wide association studies (GWAS) explain associated with CAD, we developed a candidate pathway-based GWAS by integrating expression quantitative loci analysis and mining of GWAS data with variants in a candidate pathway. Mining of GWAS data was performed to analyze variants in 32 complement system genes for positive association with CAD. Functional variants in genes showing positive association were then identified by searching existing expression quantitative loci databases and validated by real-time reverse transcription polymerase chain reaction. A follow-up case-control design was then used to determine whether the functional variants are associated with CAD in 2 independent GeneID Chinese populations. Candidate pathway-based GWAS identified positive association between variants in C3AR1 and C6 and CAD. Two functional variants, rs7842 in C3AR1 and rs4400166 in C6, were found to be associated with expression levels of C3AR1 and C6, respectively. Significant association was identified between rs7842 and CAD (P=3.99×10(-6); odds ratio, 1.47) and between rs4400166 and CAD (P=9.30×10(-3); odds ratio, 1.24) in the validation cohort. The significant findings were confirmed in the replication cohort (P=1.53×10(-5); odds ratio, 1.37 for rs7842; P=8.41×10(-3); odds ratio, 1.21 for rs4400166). Integration of GWAS with biological pathways and expression quantitative loci is effective in identifying new risk variants for CAD. Functional variants increasing C3AR1 and C6 expression were shown to confer significant risk of CAD for the first time. © 2014 American Heart Association, Inc.

  8. Cerebral blood flow associated with creative performance: a comparative study.

    Science.gov (United States)

    Chávez-Eakle, Rosa Aurora; Graff-Guerrero, Ariel; García-Reyna, Juan-Carlos; Vaugier, Víctor; Cruz-Fuentes, Carlos

    2007-11-15

    Creativity is important for social survival and individual wellbeing; science, art, philosophy and technology have been enriched and expanded by this trait. To our knowledge this is the first study probing differences in brain cerebral blood flow (CBF) between highly creative individuals (scientists and/or artists socially recognized for their contributions to their fields with creativity indexes corresponding to the 99% percentile) and average control subjects while performing a verbal task from the Torrance Tests of Creative Thinking. Additionally, we correlated CBF with creativity dimensions such as fluency, originality and flexibility. Subjects with a high creative performance showed greater CBF activity in right precentral gyrus, right culmen, left and right middle frontal gyrus, right frontal rectal gyrus, left frontal orbital gyrus, and left inferior gyrus (BA 6, 10, 11, 47, 20), and cerebellum; confirming bilateral cerebral contribution. These structures have been involved in cognition, emotion, working memory, and novelty response. The score on the three creativity dimensions--fluency, originality, and flexibility--correlated with CBF activation in right middle frontal gyrus and right rectal gyrus (Brodmann Area 6, 11). Moreover, fluency and flexibility strongly correlated with CBF in left inferior frontal gyrus and originality correlated with CBF in left superior temporal gyrus and cerebellar tonsil. These findings suggest an integration of perceptual, volitional, cognitive and emotional processes in creativity. The higher CBF found in particular brain regions of highly creative individuals during the performance of a creative task provides evidence of a specific neural network related to the creative process.

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

    Directory of Open Access Journals (Sweden)

    Unjin Shim

    2014-12-01

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

  10. Genome-Wide Association Study Reveals Novel Genes Associated with Culm Cellulose Content in Bread Wheat (Triticum aestivum, L.

    Directory of Open Access Journals (Sweden)

    Simerjeet Kaur

    2017-11-01

    Full Text Available Plant cell wall formation is a complex, coordinated and developmentally regulated process. Cellulose is the most dominant constituent of plant cell walls. Because of its paracrystalline structure, cellulose is the main determinant of mechanical strength of plant tissues. As the most abundant polysaccharide on earth, it is also the focus of cellulosic biofuel industry. To reduce culm lodging in wheat and for improved ethanol production, delineation of the variation for stem cellulose content could prove useful. We present results on the analysis of the stem cellulose content of 288 diverse wheat accessions and its genome-wide association study (GWAS. Cellulose concentration ranged from 35 to 52% (w/w. Cellulose content was normally distributed in the accessions around a mean and median of 45% (w/w. Genome-wide marker-trait association study using 21,073 SNPs helped identify nine SNPs that were associated (p < 1E-05 with cellulose content. Four strongly associated (p < 8.17E-05 SNP markers were linked to wheat unigenes, which included β-tubulin, Auxin-induced protein 5NG4, and a putative transmembrane protein of unknown function. These genes may be directly or indirectly involved in the formation of cellulose in wheat culms. GWAS results from this study have the potential for genetic manipulation of cellulose content in bread wheat and other small grain cereals to enhance culm strength and improve biofuel production.

  11. Genome‐wide association study of facial emotion recognition in children and association with polygenic risk for mental health disorders

    Science.gov (United States)

    Coleman, Jonathan R.I.; Lester, Kathryn J.; Keers, Robert; Munafò, Marcus R.; Breen, Gerome

    2017-01-01

    Emotion recognition is disrupted in many mental health disorders, which may reflect shared genetic aetiology between this trait and these disorders. We explored genetic influences on emotion recognition and the relationship between these influences and mental health phenotypes. Eight‐year‐old participants (n = 4,097) from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed the Diagnostic Analysis of Non‐Verbal Accuracy (DANVA) faces test. Genome‐wide genotype data was available from the Illumina HumanHap550 Quad microarray. Genome‐wide association studies were performed to assess associations with recognition of individual emotions and emotion in general. Exploratory polygenic risk scoring was performed using published genomic data for schizophrenia, bipolar disorder, depression, autism spectrum disorder, anorexia, and anxiety disorders. No individual genetic variants were identified at conventional levels of significance in any analysis although several loci were associated at a level suggestive of significance. SNP‐chip heritability analyses did not identify a heritable component of variance for any phenotype. Polygenic scores were not associated with any phenotype. The effect sizes of variants influencing emotion recognition are likely to be small. Previous studies of emotion identification have yielded non‐zero estimates of SNP‐heritability. This discrepancy is likely due to differences in the measurement and analysis of the phenotype. PMID:28608620

  12. 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 =

  13. The Cultural Roots of Teacher Associations: A Case Study from India

    Science.gov (United States)

    Padwad, Amol

    2016-01-01

    Teacher associations (TAs) are communities located in complex cultural spaces that may affect their functioning, vision, priorities, and policies. This case study of the English Language Teachers' Association of India (ELTAI) attempts to examine the relationship between the Association and the cultural space it inhabits, with specific reference to…

  14. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    DEFF Research Database (Denmark)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five gen...

  15. Actigraphic sleep fragmentation, efficiency and duration associate with dietary intake in the Rotterdam study

    Science.gov (United States)

    Short self-reported sleep duration is associated with dietary intake and this association may partly mediate the link between short sleep and metabolic abnormalities. Subjective sleep measures, however, may be inaccurate and biased. The objective of this study was to evaluate the associations betwee...

  16. Preliminary study on association between toxoplasmosis and breast cancer in Iran

    Directory of Open Access Journals (Sweden)

    Narges Kalantari

    2015-01-01

    Conclusions: This study did not find any significant association between toxoplasmosis and breast cancer besides higher rates of seropositivity and serointensity in patients compared with healthy volunteers.

  17. Novel genes identified in a high-density genome wide association study for nicotine dependence

    National Research Council Canada - National Science Library

    Bierut, Laura Jean; Madden, Pamela A.F; Breslau, Naomi; Johnson, Eric O; Hatsukami, Dorothy; Pomerleau, Ovide F; Swan, Gary E; Rutter, Joni; Bertelsen, Sarah; Fox, Louis; Fugman, Douglas; Goate, Alison M; Hinrichs, Anthony L; Konvicka, Karel; Martin, Nicholas G; Montgomery, Grant W; Saccone, Nancy L; Saccone, Scott F; Wang, Jen C; Chase, Gary A; Rice, John P; Ballinger, Dennis G

    .... To identify novel genes for which natural variation contributes to the development of nicotine dependence, we performed a comprehensive genome wide association study using nicotine dependent smokers...

  18. Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study

    National Research Council Canada - National Science Library

    Gelder, van, B.M; Buijsse, B; Tijhuis, M.J; Kalmijn, S; Giampaoli, S; Nissinen, A; Kromhout, D

    2007-01-01

    Objective: To investigate whether coffee consumption is associated with 10-year cognitive decline in elderly men, as results of previous studies obtained hitherto have been controversial and prospective...

  19. 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

  20. Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk.

    Science.gov (United States)

    Lindström, Sara; Thompson, Deborah J; Paterson, Andrew D; Li, Jingmei; Gierach, Gretchen L; Scott, Christopher; Stone, Jennifer; Douglas, Julie A; dos-Santos-Silva, Isabel; Fernandez-Navarro, Pablo; Verghase, Jajini; Smith, Paula; Brown, Judith; Luben, Robert; Wareham, Nicholas J; Loos, Ruth J F; Heit, John A; Pankratz, V Shane; Norman, Aaron; Goode, Ellen L; Cunningham, Julie M; deAndrade, Mariza; Vierkant, Robert A; Czene, Kamila; Fasching, Peter A; Baglietto, Laura; Southey, Melissa C; Giles, Graham G; Shah, Kaanan P; Chan, Heang-Ping; Helvie, Mark A; Beck, Andrew H; Knoblauch, Nicholas W; Hazra, Aditi; Hunter, David J; Kraft, Peter; Pollan, Marina; Figueroa, Jonine D; Couch, Fergus J; Hopper, John L; Hall, Per; Easton, Douglas F; Boyd, Norman F; Vachon, Celine M; Tamimi, Rulla M

    2014-10-24

    Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (Pbreast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (Pbreast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease-susceptibility loci.

  1. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study

    OpenAIRE

    Perera, Minoli A.; Cavallari, Larisa H; LIMDI, NITA A.; Gamazon, Eric R.; Konkashbaev, Anuar; DANESHJOU, ROXANA; Pluzhnikov, Anna; Crawford, Dana C; Wang, Jelai; Liu, Nianjun; Tatonetti, Nicholas; Bourgeois, Stephane; Takahashi, Harumi; Bradford, Yukiko; Burkley, Benjamin M

    2013-01-01

    Summary BackgroundVKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. MethodsWe did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfar...

  2. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    Science.gov (United States)

    Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van ‘t Veer, Laura J.; van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Rodríguez, Primitiva Menéndez; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Dynnes Ørsted, David; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P.E.A.; Tollenaar, RAEM.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case–case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case–control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. Results In case–case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR− than PR+ tumors (P = .001). Nulliparity (P = 3 × 10−6) and increasing age at first birth (P = 2 × 10−9) were less frequent in ER− than in ER+ tumors. Obesity (body mass index [BMI] ≥ 30 kg/m2) in younger women (≤50 years) was more frequent in ER−/PR− than in ER+/PR+ tumors (P = 1 × 10−7), whereas obesity in older women (>50 years) was less frequent in PR− than in PR+ tumors (P = 6 × 10−4). The triple-negative (ER−/PR−/HER2−) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6+ and/or epidermal growth factor receptor [EGFR]+) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case–control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER+ or PR+ tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95

  3. GWAS and admixture mapping identify different asthma-associated loci in Latinos: The GALA II Study

    Science.gov (United States)

    Galanter, Joshua M; Gignoux, Christopher R; Torgerson, Dara G; Roth, Lindsey A; Eng, Celeste; Oh, Sam S; Nguyen, Elizabeth A; Drake, Katherine A; Huntsman, Scott; Hu, Donglei; Sen, Saunak; Davis, Adam; Farber, Harold J.; Avila, Pedro C.; Brigino-Buenaventura, Emerita; LeNoir, Michael A.; Meade, Kelley; Serebrisky, Denise; Borrell, Luisa N; Rodríguez-Cintrón, William; Estrada, Andres Moreno; Mendoza, Karla Sandoval; Winkler, Cheryl A.; Klitz, William; Romieu, Isabelle; London, Stephanie J.; Gilliland, Frank; Martinez, Fernando; Bustamante, Carlos; Williams, L Keoki; Kumar, Rajesh; Rodríguez-Santana, José R.; Burchard, and Esteban G.

    2013-01-01

    Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations and replication of positive associations has been inconsistent. Objective To identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1,893) and healthy controls (n = 1,881) were recruited from five sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest p-value: rs2523924, p < 5 × 10−6). This association replicates in a meta-analysis of the EVE Asthma Consortium (p = 0.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between the 17q21 asthma in Latinos (IKZF3, lowest p-value: rs90792, OR: 0.67, 95% CI 0.61 – 0.75, p = 6 × 10−13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, while genome-wide association confirms the previously identified locus on 17q21. PMID:24406073

  4. XPAT: a toolkit to conduct cross-platform association studies with heterogeneous sequencing datasets.

    Science.gov (United States)

    Yu, Yao; Hu, Hao; Bohlender, Ryan J; Hu, Fulan; Chen, Jiun-Sheng; Holt, Carson; Fowler, Jerry; Guthery, Stephen L; Scheet, Paul; Hildebrandt, Michelle At; Yandell, Mark; Huff, Chad D

    2017-12-23

    High-throughput sequencing data are increasingly being made available to the research community for secondary analyses, providing new opportunities for large-scale association studies. However, heterogeneity in target capture and sequencing technologies often introduce strong technological stratification biases that overwhelm subtle signals of association in studies of complex traits. Here, we introduce the Cross-Platform Association Toolkit, XPAT, which provides a suite of tools designed to support and conduct large-scale association studies with heterogeneous sequencing datasets. XPAT includes tools to support cross-platform aware variant calling, quality control filtering, gene-based association testing and rare variant effect size estimation. To evaluate the performance of XPAT, we conducted case-control association studies for three diseases, including 783 breast cancer cases, 272 ovarian cancer cases, 205 Crohn disease cases and 3507 shared controls (including 1722 females) using sequencing data from multiple sources. XPAT greatly reduced Type I error inflation in the case-control analyses, while replicating many previously identified disease-gene associations. We also show that association tests conducted with XPAT using cross-platform data have comparable performance to tests using matched platform data. XPAT enables new association studies that combine existing sequencing datasets to identify genetic loci associated with common diseases and other complex traits. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Directory of Open Access Journals (Sweden)

    Vesna Boraska

    Full Text Available Brachial circumference (BC, also known as upper arm or mid arm circumference, can be used as an indicator of muscle mass and fat tissue, which are distributed differently in men and women. Analysis of anthropometric measures of peripheral fat distribution such as BC could help in understanding the complex pathophysiology behind overweight and obesity. The purpose of this study is to identify genetic variants associated with BC through a large-scale genome-wide association scan (GWAS meta-analysis. We used fixed-effects meta-analysis to synthesise summary results across 14 GWAS discovery and 4 replication cohorts comprising overall 22,376 individuals (12,031 women and 10,345 men of European ancestry. Individual analyses were carried out for men, women, and combined across sexes using linear regression and an additive genetic model: adjusted for age and adjusted for age and BMI. We prioritised signals for follow-up in two-stages. We did not detect any signals reaching genome-wide significance. The FTO rs9939609 SNP showed nominal evidence for association (p<0.05 in the age-adjusted strata for men and across both sexes. In this first GWAS meta-analysis for BC to date, we have not identified any genome-wide significant signals and do not observe robust association of previously established obesity loci with BC. Large-scale collaborations will be necessary to achieve higher power to detect loci underlying BC.

  6. Developmental Associations between Conduct Problems and Expressive Language in Early Childhood: A Population-Based Study

    OpenAIRE

    Girard, Lisa-Christine‎; Pingault, Jean-Baptiste; Doyle, Orla; Falissard, Bruno; Tremblay, Richard Ernest

    2016-01-01

    Conduct problems have been associated with poor language development, however the direction of this association in early childhood remains unclear. This study examined the longitudinal directional associations between conduct problems and expressive language ability. Children enrolled in the UK Millennium Cohort Study (N = 14, 004; 50.3 % boys) were assessed at 3 and 5 years of age. Parent reports of conduct problems and standardised assessments of expressive language were analyzed using cros...

  7. Lipoprotein-associated phospholipase A2 and coronary calcification - The Rotterdam coronary calcification study

    NARCIS (Netherlands)

    Kardys, Isabella; Oei, Hok-Hay S.; Hofman, Albert; Oudkerk, Matthijs; Witteman, Jacqueline C. M.

    Objectives: Although several studies have recently suggested that lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent predictor of coronary events, only one study has examined the association between Lp-PLA2 and coronary calcification, using young adults. We investigated the

  8. Study Finds Association between Biological Marker and Susceptibility to the Common Cold

    Science.gov (United States)

    ... H I J K L M N O P Q R S T U V W X Y Z Study Finds Association Between Biological Marker and Susceptibility to the Common Cold Share: © BananaStock Preliminary study results suggest that a biomarker may be associated with the ability of young and middle-aged people to fight off a ...

  9. An exploratory study of associations of physical activity with mental health and work engagement

    NARCIS (Netherlands)

    van Berkel, J.; Proper, K.I.; Dam, A.; Boot, C.R.L.; Bongers, P.M.; van der Beek, A.J.

    2013-01-01

    Background: Previous studies have found moderate to vigorous physical activity (MVPA) to be associated with a decreased risk of mental disorders. Although the focus in the field of psychology has shifted towards human strengths and optimal functioning, studies examining associations between MVPA and

  10. Chronic sleep reduction is associated with academic achievement and study concentration in higher education students

    NARCIS (Netherlands)

    van der Heijden, Kristiaan B; Vermeulen, M; Donjacour, Claire E H M; Gordijn, Marijke C M; Hamburger, Hans L; Meijer, Anne M; van Rijn, Karin J; Vlak, Monique; Weysen, Tim

    2017-01-01

    Inadequate sleep impairs cognitive function and has been associated with worse academic achievement in higher education students; however, studies that control for relevant background factors and include knowledge on sleep hygiene are scarce. This study examined the association of chronic sleep

  11. Chronic sleep reduction is associated with academic achievement and study concentration in higher education students

    NARCIS (Netherlands)

    van der Heijden, Kristiaan B; Vermeulen, M; Donjacour, Claire E H M; Gordijn, Marijke C M; Hamburger, Hans L; Meijer, Anne M; van Rijn, Karin J; Vlak, Monique; Weysen, Tim

    2018-01-01

    Inadequate sleep impairs cognitive function and has been associated with worse academic achievement in higher education students; however, studies that control for relevant background factors and include knowledge on sleep hygiene are scarce. This study examined the association of chronic sleep

  12. A prospective study of the association between weight changes and self-rated health

    DEFF Research Database (Denmark)

    Simonsen, Mette K; Hundrup, Yrsa A; Grønbaek, Morten

    2008-01-01

    Obesity and self-rated health (SRH) are strong predictors of morbidity and mortality but their interrelation is sparsely studied. The aim of this study was to analyse the association between weight changes and changes in SRH among women. We also examined if poor SRH at baseline was associated...... with later weight gain....

  13. Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study

    Science.gov (United States)

    OBJECTIVES: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC). BACKGROUND: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying c...

  14. Personality traits are associated with research misbehavior in Dutch scientists : A cross-sectional study

    NARCIS (Netherlands)

    Tijdink, Joeri; Bouter, Lex; Veldkamp, C.L.S.; van de Ven, Peter; Wicherts, J.M.; Smulders, Yvo; Dorta-González, Pablo

    2016-01-01

    Background Personality influences decision making and ethical considerations. Its influence on the occurrence of research misbehavior has never been studied. This study aims to determine the association between personality traits and self-reported questionable research practices and research

  15. Anxiety and depression associated with urinary incontinence. A 10-year follow-up study from the Norwegian HUNT study (EPINCONT)

    OpenAIRE

    Felde, Gunhild; Ebbesen, Marit Helen; Hunskaar, Steinar

    2017-01-01

    Aims: Firstly, to investigate the association between depression, anxiety and urinary incontinence (UI) in a 10-year longitudinal study of women. Secondly, to investigate the association between possible differences in the stress- and urgency components of UI and different severities of depression and anxiety by age groups. Methods: In a longitudinal, population-based survey study, the EPINCONT part of the HUNT study in Norway, we analyzed questionnaire data on UI, depression and anxiety f...

  16. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

    Science.gov (United States)

    Hou, Liping; Bergen, Sarah E.; Akula, Nirmala; Song, Jie; Hultman, Christina M.; Landén, Mikael; Adli, Mazda; Alda, Martin; Ardau, Raffaella; Arias, Bárbara; Aubry, Jean-Michel; Backlund, Lena; Badner, Judith A.; Barrett, Thomas B.; Bauer, Michael; Baune, Bernhard T.; Bellivier, Frank; Benabarre, Antonio; Bengesser, Susanne; Berrettini, Wade H.; Bhattacharjee, Abesh Kumar; Biernacka, Joanna M.; Birner, Armin; Bloss, Cinnamon S.; Brichant-Petitjean, Clara; Bui, Elise T.; Byerley, William; Cervantes, Pablo; Chillotti, Caterina; Cichon, Sven; Colom, Francesc; Coryell, William; Craig, David W.; Cruceanu, Cristiana; Czerski, Piotr M.; Davis, Tony; Dayer, Alexandre; Degenhardt, Franziska; Del Zompo, Maria; DePaulo, J. Raymond; Edenberg, Howard J.; Étain, Bruno; Falkai, Peter; Foroud, Tatiana; Forstner, Andreas J.; Frisén, Louise; Frye, Mark A.; Fullerton, Janice M.; Gard, Sébastien; Garnham, Julie S.; Gershon, Elliot S.; Goes, Fernando S.; Greenwood, Tiffany A.; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Heilbronner, Urs; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hipolito, Maria; Hitturlingappa, Shashi; Hoffmann, Per; Hofmann, Andrea; Jamain, Stephane; Jiménez, Esther; Kahn, Jean-Pierre; Kassem, Layla; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Koller, Daniel L.; König, Barbara; Lackner, Nina; Laje, Gonzalo; Lang, Maren; Lavebratt, Catharina; Lawson, William B.; Leboyer, Marion; Leckband, Susan G.; Liu, Chunyu; Maaser, Anna; Mahon, Pamela B.; Maier, Wolfgang; Maj, Mario; Manchia, Mirko; Martinsson, Lina; McCarthy, Michael J.; McElroy, Susan L.; McInnis, Melvin G.; McKinney, Rebecca; Mitchell, Philip B.; Mitjans, Marina; Mondimore, Francis M.; Monteleone, Palmiero; Mühleisen, Thomas W.; Nievergelt, Caroline M.; Nöthen, Markus M.; Novák, Tomas; Nurnberger, John I.; Nwulia, Evaristus A.; Ösby, Urban; Pfennig, Andrea; Potash, James B.; Propping, Peter; Reif, Andreas; Reininghaus, Eva; Rice, John; Rietschel, Marcella; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Scheftner, William A.; Schofield, Peter R.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schweizer, Barbara W.; Severino, Giovanni; Shekhtman, Tatyana; Shilling, Paul D.; Simhandl, Christian; Slaney, Claire M.; Smith, Erin N.; Squassina, Alessio; Stamm, Thomas; Stopkova, Pavla; Streit, Fabian; Strohmaier, Jana; Szelinger, Szabolcs; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Vieta, Eduard; Volkert, Julia; Witt, Stephanie H.; Wright, Adam; Zandi, Peter P.; Zhang, Peng; Zollner, Sebastian; McMahon, Francis J.

    2016-01-01

    Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P =  5.87 × 10 − 9; odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P =  4.53 × 10 − 9; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS. PMID:27329760

  17. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

    Science.gov (United States)

    Fox, Ervin R.; Young, J. Hunter; Li, Yali; Dreisbach, Albert W.; Keating, Brendan J.; Musani, Solomon K.; Liu, Kiang; Morrison, Alanna C.; Ganesh, Santhi; Kutlar, Abdullah; Ramachandran, Vasan S.; Polak, Josef F.; Fabsitz, Richard R.; Dries, Daniel L.; Farlow, Deborah N.; Redline, Susan; Adeyemo, Adebowale; Hirschorn, Joel N.; Sun, Yan V.; Wyatt, Sharon B.; Penman, Alan D.; Palmas, Walter; Rotter, Jerome I.; Townsend, Raymond R.; Doumatey, Ayo P.; Tayo, Bamidele O.; Mosley, Thomas H.; Lyon, Helen N.; Kang, Sun J.; Rotimi, Charles N.; Cooper, Richard S.; Franceschini, Nora; Curb, J. David; Martin, Lisa W.; Eaton, Charles B.; Kardia, Sharon L.R.; Taylor, Herman A.; Caulfield, Mark J.; Ehret, Georg B.; Johnson, Toby; Chakravarti, Aravinda; Zhu, Xiaofeng; Levy, Daniel; Munroe, Patricia B.; Rice, Kenneth M.; Bochud, Murielle; Johnson, Andrew D.; Chasman, Daniel I.; Smith, Albert V.; Tobin, Martin D.; Verwoert, Germaine C.; Hwang, Shih-Jen; Pihur, Vasyl; Vollenweider, Peter; O'Reilly, Paul F.; Amin, Najaf; Bragg-Gresham, Jennifer L.; Teumer, Alexander; Glazer, Nicole L.; Launer, Lenore; Zhao, Jing Hua; Aulchenko, Yurii; Heath, Simon; Sõber, Siim; Parsa, Afshin; Luan, Jian'an; Arora, Pankaj; Dehghan, Abbas; Zhang, Feng; Lucas, Gavin; Hicks, Andrew A.; Jackson, Anne U.; Peden, John F.; Tanaka, Toshiko; Wild, Sarah H.; Rudan, Igor; Igl, Wilmar; Milaneschi, Yuri; Parker, Alex N.; Fava, Cristiano; Chambers, John C.; Kumari, Meena; JinGo, Min; van der Harst, Pim; Kao, Wen Hong Linda; Sjögren, Marketa; Vinay, D.G.; Alexander, Myriam; Tabara, Yasuharu; Shaw-Hawkins, Sue; Whincup, Peter H.; Liu, Yongmei; Shi, Gang; Kuusisto, Johanna; Seielstad, Mark; Sim, Xueling; Nguyen, Khanh-Dung Hoang; Lehtimäki, Terho; Matullo, Giuseppe; Wu, Ying; Gaunt, Tom R.; Charlotte Onland-Moret, N.; 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.; Campbell, Harry; 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.; Hernandez, Dena; Najjar, Samer; McArdle, Wendy L.; Hadley, David; Brown, Morris J.; 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; Bis, Joshua C.; Kähönen, Mika; Viikari, Jorma; Adair, Linda S.; Lee, Nanette R.; Chen, Ming-Huei; Olden, Matthias; Pattaro, Cristian; Hoffman Bolton, Judith A.; Köttgen, Anna; Bergmann, Sven; Mooser, Vincent; Chaturvedi, Nish; Frayling, Timothy M.; Islam, Muhammad; Jafar, Tazeen H.; Erdmann, Jeanette; Kulkarni, Smita R.; Bornstein, Stefan R.; Grässler, Jürgen; Groop, Leif; Voight, Benjamin F.; Kettunen, Johannes; Howard, Philip; Taylor, Andrew; Guarrera, Simonetta; Ricceri, Fulvio; Emilsson, Valur; Plump, Andrew; Barroso, Inês; Khaw, Kay-Tee; Weder, Alan B.; Hunt, Steven C.; Bergman, Richard N.; Collins, Francis S.; Bonnycastle, Lori L.; Scott, Laura J.; Stringham, Heather M.; Peltonen, Leena; Perola, Markus; Vartiainen, Erkki; Brand, Stefan-Martin; Staessen, Jan A.; Wang, Thomas J.; Burton, Paul R.; SolerArtigas, Maria; Dong, Yanbin; Snieder, Harold; Wang, Xiaoling; Zhu, Haidong; Lohman, Kurt K.; Rudock, Megan E.; Heckbert, Susan R.; Smith, Nicholas L.; Wiggins, Kerri L.; Shriner, Daniel; Veldre, Gudrun; Viigimaa, Margus; Kinra, Sanjay; Prabhakaran, Dorairajan; Tripathy, Vikal; Langefeld, Carl D.; Rosengren, Annika; Thelle, Dag S.; MariaCorsi, Anna; 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; Meitinger, Thomas; Wichmann, H.-Erich; Cho, Yoon Shin; Kim, Hyung-Lae; Lee, Jong-Young; Scott, James; Sehmi, Joban S.; Zhang, Weihua; Hedblad, Bo; Nilsson, Peter; Smith, George Davey; Wong, Andrew; Narisu, Narisu; Stančáková, Alena; Raffel, Leslie J.; Yao, Jie; Kathiresan, Sekar; O'Donnell, Chris; Schwartz, Steven M.; Arfan Ikram, M.; Longstreth, Will T.; Seshadri, Sudha; Shrine, Nick R.G.; Wain, Louise V.; Morken, Mario A.; Swift, Amy J.; Laitinen, Jaana; Prokopenko, Inga; Zitting, Paavo; Cooper, Jackie A.; Humphries, Steve E.; Danesh, John; Rasheed, Asif; Goel, Anuj; Hamsten, Anders; Watkins, Hugh; Bakker, Stephan J.L.; van Gilst, Wiek H.; Janipalli, Charles S.; Radha Mani, K.; Yajnik, Chittaranjan S.; Hofman, Albert; Mattace-Raso, Francesco U.S.; Oostra, Ben A.; Demirkan, Ayse; Isaacs, Aaron; Rivadeneira, Fernando; Lakatta, Edward G.; Orru, Marco; Scuteri, Angelo; Ala-Korpela, Mika; Kangas, Antti J.; Lyytikäinen, Leo-Pekka; Soininen, Pasi; Tukiainen, Taru; Würz, Peter; Twee-Hee Ong, Rick; Dörr, Marcus; Kroemer, Heyo K.; Völker, Uwe; Völzke, Henry; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Zelenika, Diana; Deloukas, Panos; Mangino, Massimo; Spector, Tim D.; Zhai, Guangju; Meschia, James F.; Nalls, Michael A.; Sharma, Pankaj; Terzic, Janos; Kranthi Kumar, M.J.; Denniff, Matthew; Zukowska-Szczechowska, Ewa; Wagenknecht, Lynne E.; Fowkes, Gerald R.; Charchar, Fadi J.; Schwarz, Peter E.H.; Hayward, Caroline; Guo, Xiuqing; Bots, Michiel L.; Brand, Eva; Samani, Nilesh J.; Polasek, Ozren; Talmud, Philippa J.; Nyberg, Fredrik; Kuh, Diana; Laan, Maris; Hveem, Kristian; Palmer, Lyle J.; van der Schouw, Yvonne T.; Casas, Juan P.; Mohlke, Karen L.; Vineis, Paolo; Raitakari, Olli; Wong, Tien Y.; Shyong Tai, E.; Laakso, Markku; Rao, Dabeeru C.; Harris, Tamara B.; Morris, Richard W.; Dominiczak, Anna F.; Kivimaki, Mika; Marmot, Michael G.; Miki, Tetsuro; Saleheen, Danish; Chandak, Giriraj R.; Coresh, Josef; Navis, Gerjan; Salomaa, Veikko; Han, Bok-Ghee; Kooner, Jaspal S.; Melander, Olle; Ridker, Paul M.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wright, Alan F.; Wilson, James F.; Ferrucci, Luigi; Farrall, Martin; Tuomilehto, Jaakko; Pramstaller, Peter P.; Elosua, Roberto; Soranzo, Nicole; Sijbrands, Eric J.G.; Altshuler, David; Loos, Ruth J.F.; Shuldiner, Alan R.; Gieger, Christian; Meneton, Pierre; Uitterlinden, Andre G.; Wareham, Nicholas J.; Gudnason, Vilmundur; Rettig, Rainer; Uda, Manuela; Strachan, David P.; Witteman, Jacqueline C.M.; Hartikainen, Anna-Liisa; Beckmann, Jacques S.; Boerwinkle, Eric; Boehnke, Michael; Larson, Martin G.; Järvelin, Marjo-Riitta; Psaty, Bruce M.; Abecasis, Gonçalo R.; Elliott, Paul; van Duijn , Cornelia M.; Newton-Cheh, Christopher

    2011-01-01

    The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. PMID:21378095

  18. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

    Science.gov (United States)

    Hou, Liping; Heilbronner, Urs; Degenhardt, Franziska; Adli, Mazda; Akiyama, Kazufumi; Akula, Nirmala; Ardau, Raffaella; Arias, Bárbara; Backlund, Lena; Banzato, Claudio E M; Benabarre, Antoni; Bengesser, Susanne; Bhattacharjee, Abesh Kumar; Biernacka, Joanna M; Birner, Armin; Brichant-Petitjean, Clara; Bui, Elise T; Cervantes, Pablo; Chen, Guo-Bo; Chen, Hsi-Chung; Chillotti, Caterina; Cichon, Sven; Clark, Scott R; Colom, Francesc; Cousins, David A; Cruceanu, Cristiana; Czerski, Piotr M; Dantas, Clarissa R; Dayer, Alexandre; Étain, Bruno; Falkai, Peter; Forstner, Andreas J; Frisén, Louise; Fullerton, Janice M; Gard, Sébastien; Garnham, Julie S; Goes, Fernando S; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Herms, Stefan; Hoffmann, Per; Hofmann, Andrea; Jamain, Stephane; Jiménez, Esther; Kahn, Jean-Pierre; Kassem, Layla; Kittel-Schneider, Sarah; Kliwicki, Sebastian; König, Barbara; Kusumi, Ichiro; Lackner, Nina; Laje, Gonzalo; Landén, Mikael; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G; Jaramillo, Carlos A López; MacQueen, Glenda; Manchia, Mirko; Martinsson, Lina; Mattheisen, Manuel; McCarthy, Michael J; McElroy, Susan L; Mitjans, Marina; Mondimore, Francis M; Monteleone, Palmiero; Nievergelt, Caroline M; Nöthen, Markus M; Ösby, Urban; Ozaki, Norio; Perlis, Roy H; Pfennig, Andrea; Reich-Erkelenz, Daniela; Rouleau, Guy A; Schofield, Peter R; Schubert, K Oliver; Schweizer, Barbara W; Seemüller, Florian; Severino, Giovanni; Shekhtman, Tatyana; Shilling, Paul D; Shimoda, Kazutaka; Simhandl, Christian; Slaney, Claire M; Smoller, Jordan W; Squassina, Alessio; Stamm, Thomas; Stopkova, Pavla; Tighe, Sarah K; Tortorella, Alfonso; Turecki, Gustavo; Volkert, Julia; Witt, Stephanie; Wright, Adam; Young, L Trevor; Zandi, Peter P; Potash, James B; DePaulo, J Raymond; Bauer, Michael; Reininghaus, Eva Z; Novák, Tomas; Aubry, Jean-Michel; Maj, Mario; Baune, Bernhard T; Mitchell, Philip B; Vieta, Eduard; Frye, Mark A; Rybakowski, Janusz K; Kuo, Po-Hsiu; Kato, Tadafumi; Grigoroiu-Serbanescu, Maria; Reif, Andreas; Del Zompo, Maria; Bellivier, Frank; Schalling, Martin; Wray, Naomi R; Kelsoe, John R; Alda, Martin; Rietschel, Marcella; McMahon, Francis J; Schulze, Thomas G

    2016-03-12

    Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. Deutsche Forschungsgemeinschaft, National Institute of Mental Health

  19. Genome-wide association studies identified three independent polymorphisms associated with α-tocopherol content in maize kernels.

    Science.gov (United States)

    Li, Qing; Yang, Xiaohong; Xu, Shutu; Cai, Ye; Zhang, Dalong; Han, Yingjia; Li, Lin; Zhang, Zuxin; Gao, Shibin; Li, Jiansheng; Yan, Jianbing

    2012-01-01

    Tocopherols are a class of four natural compounds that can provide nutrition and function as antioxidant in both plants and animals. Maize kernels have low α-tocopherol content, the compound with the highest vitamin E activity, thus, raising the risk of vitamin E deficiency in human populations relying on maize as their primary vitamin E source. In this study, two insertion/deletions (InDels) within a gene encoding γ-tocopherol methyltransferase, Zea mays VTE4 (ZmVTE4), and a single nucleotide polymorphism (SNP) located ~85 kb upstream of ZmVTE4 were identified to be significantly associated with α-tocopherol levels in maize kernels by conducting an association study with a panel of ~500 diverse inbred lines. Linkage analysis in three populations that segregated at either one of these three polymorphisms but not at the other two suggested that the three polymorphisms could affect α-tocopherol content independently. Furthermore, we found that haplotypes of the two InDels could explain ∼33% of α-tocopherol variation in the association panel, suggesting ZmVTE4 is a major gene involved in natural phenotypic variation of α-tocopherol. One of the two InDels is located within the promoter region and associates with ZmVTE4 transcript level. This information can not only help in understanding the underlying mechanism of natural tocopherol variations in maize kernels, but also provide valuable markers for marker-assisted breeding of α-tocopherol content in maize kernels, which will then facilitate the improvement of maize as a better source of daily vitamin E nutrition.

  20. Genome-wide association studies identified three independent polymorphisms associated with α-tocopherol content in maize kernels.

    Directory of Open Access Journals (Sweden)

    Qing Li

    Full Text Available Tocopherols are a class of four natural compounds that can provide nutrition and function as antioxidant in both plants and animals. Maize kernels have low α-tocopherol content, the compound with the highest vitamin E activity, thus, raising the risk of vitamin E deficiency in human populations relying on maize as their primary vitamin E source. In this study, two insertion/deletions (InDels within a gene encoding γ-tocopherol methyltransferase, Zea mays VTE4 (ZmVTE4, and a single nucleotide polymorphism (SNP located ~85 kb upstream of ZmVTE4 were identified to be significantly associated with α-tocopherol levels in maize kernels by conducting an association study with a panel of ~500 diverse inbred lines. Linkage analysis in three populations that segregated at either one of these three polymorphisms but not at the other two suggested that the three polymorphisms could affect α-tocopherol content independently. Furthermore, we found that haplotypes of the two InDels could explain ∼33% of α-tocopherol variation in the association panel, suggesting ZmVTE4 is a major gene involved in natural phenotypic variation of α-tocopherol. One of the two InDels is located within the promoter region and associates with ZmVTE4 transcript level. This information can not only help in understanding the underlying mechanism of natural tocopherol variations in maize kernels, but also provide valuable markers for marker-assisted breeding of α-tocopherol content in maize kernels, which will then facilitate the improvement of maize as a better source of daily vitamin E nutrition.

  1. A candidate gene association study of bone mineral density in an Iranian population.

    Directory of Open Access Journals (Sweden)

    Seyed Alireza Dastgheib

    2016-10-01

    Full Text Available The genetic epidemiology of variation in bone mineral density (BMD and osteoporosis is not well studied in Iranian populations and needs more research. We report a candidate gene association study of BMD variation in a healthy cross sectional study of 501 males and females sampled from the IMOS study Shiraz, Iran. We selected to study the association with 21 SNPs located in the 7 candidate genes LRP5, RANK, RANKL, OPG, P2RX7, VDR and ESR1. BMD was measured at the three sites L2-L4, neck of femur and total hip. Association between BMD and each SNP was assessed using multiple linear regression assuming an allele dose (additive effect on BMD (adjusted for age and sex. Statistically significant (at the unadjusted 5% level associations were seen with 7 SNPs in 5 of the candidate genes. Two SNPs showed statistically significant association with more than one BMD site. Significant association was seen between BMD at all three sites with the VDR SNP rs731246 (L2-L4 p=0.038; neck of femur p=0.001 and total hip p<0.001. The T allele was consistently associated with lower BMD than the C allele. Significant association was also seen for the P2RX7 SNP rs3751143 where the G allele was consistently associated with lower BMD than the T allele, (L2-L4 p=0.069; neck of femur p=0.024, total hip p=0.045.

  2. A Genome-Wide Association Study Provides New Evidence That CACNA1C Gene is Associated With Diabetic Cataract

    Science.gov (United States)

    Chang, Cheng; Zhang, Kaida; Veluchamy, Abirami; Hébert, Harry L.; Looker, Helen C.; Colhoun, Helen M.; Palmer, Colin N. A.; Meng, Weihua

    2016-01-01

    Purpose Diabetic cataract is one of the major eye complications of diabetes. It was reported that cataract occurs two to five times more frequently in patients with diabetes compared with those with no diabetes. The purpose of this study was to identify genetic contributors of diabetic cataract based on a genome-wide association approach using a well-defined Scottish diabetic cohort. Methods We adapted linked e-health records to define diabetic cataract. A diabetic cataract case in this study was defined as a type 2 diabetic patient who has ever been recorded in the linked e-health records to have cataracts in both eyes or who had previous cataract extraction surgeries in at least one eye. A control in this study was defined as a type 2 diabetic individual who has never been diagnosed as cataract in the linked e-health records and had no history of cataract surgeries. A standard genome-wide association approach was applied. Results Overall, we have 2341 diabetic cataract cases and 2878 controls in the genetics of diabetes audit and research in Tayside Scotland (GoDARTS) dataset. We found that the P value of rs2283290 in the CACNA1C gene was 8.81 × 10−10, which has reached genome-wide significance. We also identified that the blood calcium level was statistically different between diabetic cataract cases and controls. Conclusions We identified supporting evidence that CACNA1C gene is associated with diabetic cataract. The role of calcium in the cataractogenesis needs to be reevaluated in future studies. PMID:27124316

  3. A case-control study identifying chromosomal polymorphic variations as forms of epigenetic alterations associated with the infertility phenotype

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Athalye, Arundhati S; Madon, Prochi F

    2009-01-01

    To study the association of chromosomal polymorphic variations with infertility and subfertility.......To study the association of chromosomal polymorphic variations with infertility and subfertility....

  4. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

    NARCIS (Netherlands)

    A. Dehghan (Abbas); J.C. Bis (Joshua); C.C. White (Charles); A.V. Smith (Albert V.); A.C. Morrison (Alanna); L.A. Cupples (Adrienne); S. Trompet (Stella); D.I. Chasman (Daniel I.); T. Lumley (Thomas); U. Völker (Uwe); B.M. Buckley (Brendan M.); J. Ding (Jingzhong); M.K. Jensen (Majken K.); A.R. Folsom (Aaron R.); S.B. Kritchevsky (Stephen); C.J. Girman (Cynthia J.); I. Ford; M. Dörr (Marcus); V. Salomaa (Veikko); A.G. Uitterlinden (André); G. Eiriksdottir (Gudny); R.S. Vasan (Ramachandran S.); N. Franceschini (Nora); C. Carty (Cara); J. Virtamo (Jarmo); S. Demissie (Serkalem); P. Amouyel (Philippe); D. Arveiler (Dominique); S.R. Heckbert (Susan); J. Ferrieres (Jean); P. Ducimetiere (P.); N.L. Smith (Nicholas); Y.A. Wang (Ying); D.S. Siscovick (David); K.M. Rice (Kenneth); P.-G. Wiklund (Per-Gunnar); K.D. Taylor (Kent); A. Evans (Alun); F. Kee (Frank); J.I. Rotter (Jerome I.); J. Karvanen (Juha); K. Kuulasmaa (Kari); G. Heiss (Gerardo); P. Kraft (Peter); L.J. Launer (Lenore); A. Hofman (Albert); M.R.P. Markus (Marcello R.P.); L.M. Rose (Lynda); K. Silander (Kaisa); P.J. Wagner (Peter); E.J. Benjamin (Emelia); K. Lohman (Kurt); D.J. Stott (David. J.); F. Rivadeneira Ramirez (Fernando); T.B. Harris (Tamara); D. Levy (Daniel); Y. Liu (Yongmei); E.B. Rimm (Eric B.); J.W. Jukema (Jan Wouter); H. Volzke (Henry); P.M. Ridker (Paul M.); S. Blankenberg (Stefan); O.H. Franco (Oscar); V. Gudnason (Vilmundur); B.M. Psaty (Bruce); E.A. Boerwinkle (Eric); C.J. O'Donnell (Christopher J.)

    2016-01-01

    textabstractBackground Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stageGWAS analysis

  5. Genome Wide Association Study Identifies 20 Novel Promising Genes Associated with Milk Fatty Acid Traits in Chinese Holstein

    Science.gov (United States)

    Li, Cong; Sun, Dongxiao; Zhang, Shengli; Wang, Sheng; Wu, Xiaoping; Zhang, Qin; Liu, Lin; Li, Yanhua; Qiao, Lv

    2014-01-01

    Detecting genes associated with milk fat composition could provide valuable insights into the complex genetic networks of genes underling variation in fatty acids synthesis and point towards opportunities for changing milk fat composition via selective breeding. In this study, we conducted a genome-wide association study (GWAS) for 22 milk fatty acids in 784 Chinese Holstein cows with the PLINK software. Genotypes were obtained with the Illumina BovineSNP50 Bead chip and a total of 40,604 informative, high-quality single nucleotide polymorphisms (SNPs) were used. Totally, 83 genome-wide significant SNPs and 314 suggestive significant SNPs associated with 18 milk fatty acid traits were detected. Chromosome regions that affect milk fatty acid traits were mainly observed on BTA1, 2, 5, 6, 7, 9, 13, 14, 18, 19, 20, 21, 23, 26 and 27. Of these, 146 SNPs were associated with more than one milk fatty acid trait; most of studied fatty acid traits were significant associated with multiple SNPs, especially C18:0 (105 SNPs), C18 index (93 SNPs), and C14 index (84 SNPs); Several SNPs are close to or within the DGAT1, SCD1 and FASN genes which are well-known to affect milk composition traits of dairy cattle. Combined with the previously reported QTL regions and the biological functions of the genes, 20 novel promising candidates for C10:0, C12:0, C14:0, C14:1, C14 index, C18:0, C18:1n9c, C18 index, SFA, UFA and SFA/UFA were found, which composed of HTR1B, CPM, PRKG1, MINPP1, LIPJ, LIPK, EHHADH, MOGAT1, ECHS1, STAT1, SORBS1, NFKB2, AGPAT3, CHUK, OSBPL8, PRLR, IGF1R, ACSL3, GHR and OXCT1. Our findings provide a groundwork for unraveling the key genes and causal mutations affecting milk fatty acid traits in dairy cattle. PMID:24858810

  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. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

    Song, H.; Koessler, T.; Ahmed, S.

    2008-01-01

    test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...

  8. A Genome-Wide Association Study Identifies the Genomic Region Associated with Shell Color in Yesso Scallop, Patinopecten yessoensis.

    Science.gov (United States)

    Zhao, Liang; Li, Yangping; Li, Yajuan; Yu, Jiachen; Liao, Huan; Wang, Shuyue; Lv, Jia; Liang, Jun; Huang, Xiaoting; Bao, Zhenmin

    2017-06-01

    The shell color polymorphism widely exists in economic shellfish, which not only results in a better visual perception but also shows great value as an economic trait for breeding. Small numbers of reddish-orange shell Yesso scallops, Patinopecten yessoensis, were found in cultured populations compared to the brown majority. In this study, a genome-wide association study was conducted to understand the genetic basis of shell color. Sixty-six 2b-RAD libraries with equal numbers of reddish-orange and brown shell individuals were constructed and sequenced using the Illumina HiSeq 2000 platform. A total of 322,332,684 high-quality reads were obtained, and the average sequencing depth was 18.4×. One genomic region on chromosome 11 that included 239 single-nucleotide polymorphisms (SNPs) was identified as significantly associated with shell color. After verification by high-resolution melting in another population, two SNPs were selected as specific loci for reddish-orange shell color. These two SNPs could be used to improve the selective breeding progress of true-breeding strains with complete reddish-orange scallops. In addition, within the significantly associated genomic region, candidate genes were identified using marker sequences to search the draft genome of Yesso scallop. Three genes (LDLR, FRIS, and FRIY) with known functions in carotenoid metabolism were identified. Further study using high-performance liquid chromatography proved that the relative level of carotenoids in the reddish-orange shells was 40 times higher than that in the brown shells. These results suggested that the accumulation of carotenoids contributes to the formation of reddish-orange shells.

  9. Replication of Prostate Cancer Risk Variants in a Danish Case-Control Association Study

    DEFF Research Database (Denmark)

    Bentzon, Diem Nguyen; Nyegaard, Mette; Børglum, Anders

    2012-01-01

    Background: Prostate cancer is one of the main causes for cancer morbidity and mortality in Western countries. Recently, several single nucleotide polymorphisms (SNPs) associated with prostate cancer have been identified in genome-wide association studies and multiple variant models have been...... developed to predict prostate cancer risk. The association between genetic markers and clinico-pathological tumor variables has, however, been inconsistent. Methods and Materials: A total of 32 previously identified prostate cancer-associated risk SNPs were genotyped in 648 prostate cancer cases and 526 age...... assays and associations between SNPs, prostate cancer risk, and clinico-pathological variables were assessed. Results: Seventeen SNPs were successfully replicated in our case-control study and the association estimates were consistent with previous reports. Four markers were excluded from further...

  10. Association Between Screen-Detected Gallstone Disease and Cancer in a Cohort Study

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue; Jørgensen, Torben

    2017-01-01

    Background & Aims: Knowledge of temporal associations between screen-detected gallstone disease and specific cancers is limited. The objective of this study was to determine if screen-detected gallstones or cholecystectomy are associated with occurrence of gastrointestinal and nongastrointestinal...... ratio, 1.50; 95% confidence interval, 1.12-2.01). Right-side colon cancer was also associated with gallstone disease (2.57% of patients with gallstone disease vs 0.96% without; hazard ratio, 2.04; 95% confidence interval, 1.10-3.78). Pancreatic, esophageal, gastric, pooled colorectal, left-side colon...... nongastrointestinal and prostate cancers were not associated with gallstone disease. Conclusions: Screen-detected gallstone disease in the general population is associated with pooled gastrointestinal and right-side colon cancers. These associations are not due to detection bias or cholecystectomy. Further studies...

  11. The multistep road to ventilator-associated lung abscess: A retrospective study of S.aureus ventilator-associated pneumonia.

    Science.gov (United States)

    Mounier, Roman; Lobo, David; Voulgaropoulos, Julia; Martin, Mathieu; Aït-Mamar, Bouziane; Bitot, Valérie; Jost, Paul-Henri; Birnbaum, Ron; Nebbad, Biba; Cook, Fabrice; Dhonneur, Gilles

    2017-01-01

    We observed some cases of lung abscess (LA) in ICU patients suffering S.aureus ventilator-associated pneumonia (S.aureus-VAP). We aimed to assess which of the host and/or bacteria-related features are associated with LA. We conducted a retrospective study from January 2009 to July 2013 in a trauma surgical ICU within a teaching hospital. All adult patients presenting with S.aureus-VAP were included. We compared two groups of patients according to the formation or not of LA concomitantly to S.aureus-VAP. Seventy-nine S.aureus-VAP patients, predominantly males (85%) of rather young age (mean [SD]: 35yr [21-64]) with severe trauma (initial Simplified Acute Score II = 42 [32-52]) related-ICU admission, were included. Among them, 10 (14%) developed LA. Patient's characteristics significantly associated with LA development were: a younger age (p = 0.003), road traffic accidents admission (p = 0.017), head injury (p = 0.002), lower Glasgow Coma Scale (p = 0.009), blunt chest trauma (p = 0.01) pneumothorax (p = 0.01) and lung contusions (p = 0.002). No microbiological factors were significantly associated with LA formation. Abscesses were mostly bilateral, ≥5 cm of diameter and with a posterior location. Our results do not favor a specific virulence of S.aureus, but rather highlight the role of multiple insults to the lung, promoting LA formation. Despite a similar severity score, patients with LA had more serious trauma, combining severe both chest and head insults.

  12. Association between Dietary Patterns and the Indicators of Obesity among Chinese: A Cross-Sectional Study

    OpenAIRE

    Shu, Long; Zheng, Pei-Fen; Zhang, Xiao-Yan; Si, Cai-Juan; Yu, Xiao-Long; Gao, Wei; Zhang, Lun; Liao, Dan

    2015-01-01

    No previous study has investigated dietary pattern in association with obesity risk in a middle-aged Chinese population. The purpose of this study was to evaluate the associations between dietary patterns and the risk of obesity in the city of Hangzhou, the capital of Zhejiang Province, east China. In this cross-sectional study of 2560 subjects aged 45–60 years, dietary intakes were evaluated using a semi-quantitative food frequency questionnaire (FFQ). All anthropometric measurements were ob...

  13. Analysis of case-control association studies with known risk variants

    OpenAIRE

    Zaitlen, Noah; Pasaniuc, Bogdan; Patterson, Nick; Pollack, Samuela; Voight, Benjamin; Groop, Leif; Altshuler, David; Henderson, Brian E.; Laurence N Kolonel; Le Marchand, Loic; Waters, Kevin; Haiman, Christopher A.; Stranger, Barbara E.; Dermitzakis, Emmanouil; Kraft, Peter

    2017-01-01

    Motivation: The question of how to best use information from known associated variants when conducting disease association studies has yet to be answered. Some studies compute a marginal P-value for each Several Nucleotide Polymorphisms independently, ignoring previously discovered variants. Other studies include known variants as covariates in logistic regression, but a weakness of this standard conditioning strategy is that it does not account for disease prevalence and non-random ascertain...

  14. A genome-wide association study of body mass index across early life and childhood

    OpenAIRE

    Warrington, N.; Howe, L.; Paternoster, L; Kaakinen, M; Herrala, S; Huikari, V.; Wu, Y.; Kemp, J.; Timpson, N; St Pourcain, B; Smith, G.; Tilling, K; Jarvelin, M.; Pennell, C; Evans, D.

    2015-01-01

    Background: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood. Methods: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77 967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Ra...

  15. FastANOVA: an Efficient Algorithm for Genome-Wide Association Study

    OpenAIRE

    Zhang, Xiang; Zou, Fei; Wang, Wei

    2008-01-01

    Studying the association between quantitative phenotype (such as height or weight) and single nucleotide polymorphisms (SNPs) is an important problem in biology. To understand underlying mechanisms of complex phenotypes, it is often necessary to consider joint genetic effects across multiple SNPs. ANOVA (analysis of variance) test is routinely used in association study. Important findings from studying gene-gene (SNP-pair) interactions are appearing in the literature. However, the number of S...

  16. Association of diabetes and cancer mortality in American Indians: the Strong Heart Study

    OpenAIRE

    Best, Lyle G.; García-Esquinas, Esther; Yeh, Jeun-Liang; Yeh, Fawn; Zhang, Ying; Lee, Elisa T.; Howard, Barbara V.; Farley, John H.; Welty, Thomas K.; RHOADES, DOROTHY A.; Rhoades, Everett R.; UMANS, Jason G.; Navas-Acien, Ana

    2015-01-01

    Purpose The metabolic abnormalities that accompany diabetes mellitus are associated with an increased risk of many cancers. These associations, however, have not been well studied in American Indian populations, which experience a high prevalence of diabetes. The Strong Heart Study is a population-based, prospective cohort study with extensive characterization of diabetes status. Methods Among a total cohort of 4,419 participants who were followed for up to 20 years, 430 cancer deaths were id...

  17. A General Framework for Association Tests With Multivariate Traits in Large-Scale Genomics Studies

    OpenAIRE

    He, Qianchuan; Avery, Christy L.; Lin, Dan-Yu

    2013-01-01

    Genetic association studies often collect data on multiple traits that are correlated. Discovery of genetic variants influencing multiple traits can lead to better understanding of the etiology of complex human diseases. Conventional univariate association tests may miss variants that have weak or moderate effects on individual traits. We propose several multivariate test statistics to complement univariate tests. Our framework covers both studies of unrelated individuals and family studies a...

  18. Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses.

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    Full Text Available Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS approach using principle component analysis(PCA. In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.

  19. Chronic sleep reduction is associated with academic achievement and study concentration in higher education students.

    Science.gov (United States)

    van der Heijden, Kristiaan B; Vermeulen, Marije C M; Donjacour, Claire E H M; Gordijn, Marijke C M; Hamburger, Hans L; Meijer, Anne M; van Rijn, Karin J; Vlak, Monique; Weysen, Tim

    2017-09-07

    Inadequate sleep impairs cognitive function and has been associated with worse academic achievement in higher education students; however, studies that control for relevant background factors and include knowledge on sleep hygiene are scarce. This study examined the association of chronic sleep reduction (i.e. symptoms of chronic sleep reduction such as shortness of sleep, sleepiness and irritation), subjective sleep quality and sleep hygiene knowledge with academic achievement (grades and study credits) and study concentration among 1378 higher education students (71% female, mean age 21.73 years, SD = 3.22) in the Netherlands. Demographic, health, lifestyle and study behaviour characteristics were included as covariates in hierarchical regression analyses. After controlling for significant covariates, only chronic sleep reduction remained a significant predictor of lower grades (last exam, average in current academic year). Better sleep quality and sleep hygiene knowledge were associated with better academic achievement, but significance was lost after controlling for covariates, except for a remaining positive association between sleep hygiene beliefs and grades in the current academic year. Moreover, better sleep quality and lower scores on chronic sleep reduction were associated with better study concentration after controlling for significant covariates. To conclude, chronic sleep reduction is associated with academic achievement and study concentration in higher education students. Inadequate sleep hygiene knowledge is moderately associated with worse academic achievement. Future research should investigate whether sleep hygiene interventions improve academic achievement in students of higher education. © 2017 European Sleep Research Society.

  20. The Potentiation of Associative Memory by Emotions: An Event-Related FMRI Study

    Directory of Open Access Journals (Sweden)

    David Luck

    2014-01-01

    Full Text Available Establishing associations between pieces of information is related to the medial temporal lobe (MTL. However, it remains unclear how emotions affect memory for associations and, consequently, MTL activity. Thus, this event-related fMRI study attempted to identify neural correlates of the influence of positive and negative emotions on associative memory. Twenty-five participants were instructed to memorize 90 pairs of standardized pictures during a scanned encoding phase. Each pair was composed of a scene and an unrelated object. Trials were neutral, positive, or negative as a function of the emotional valence of the scene. At the behavioral level, participants exhibited better memory retrieval for both emotional conditions relative to neutral trials. Within the right MTL, a functional dissociation was observed, with entorhinal activation elicited by emotional associations, posterior parahippocampal activation elicited by neutral associations, and hippocampal activation elicited by both emotional and neutral associations. In addition, emotional associations induced greater activation than neutral trials in the right amygdala. This fMRI study shows that emotions are associated with the performance improvement of associative memory, by enhancing activity in the right amygdala and the right entorhinal cortex. It also provides evidence for a rostrocaudal specialization within the MTL regarding the emotional valence of associations.

  1. Statistical methods for genetic association studies with response-selective sampling designs

    NARCIS (Netherlands)

    Balliu, Brunilda

    2015-01-01

    This dissertation describes new statistical methods designed to improve the power of genetic association studies. Of particular interest are studies with a response-selective sampling design, i.e. case-control studies of unrelated individuals and case-control studies of family members. The

  2. Fetal and maternal candidate single nucleotide polymorphism associations with cerebral palsy: a case-control study.

    Science.gov (United States)

    O'Callaghan, Michael E; Maclennan, Alastair H; Gibson, Catherine S; McMichael, Gai L; Haan, Eric A; Broadbent, Jessica L; Goldwater, Paul N; Painter, Jodie N; Montgomery, Grant W; Dekker, Gus A

    2012-02-01

    Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions. DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ(2) test. There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association. Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports.

  3. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    Science.gov (United States)

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur; Ntzani, Evangelia E; Bos, Steffan D; Esko, Tonu; Evans, Daniel S; Metrustry, Sarah; Panoutsopoulou, Kalliope; Ramos, Yolande F M; Thorleifsson, Gudmar; Tsilidis, Konstantinos K; Arden, Nigel; Aslam, Nadim; Bellamy, Nicholas; Birrell, Fraser; Blanco, Francisco J; Carr, Andrew; Chapman, Kay; Day-Williams, Aaron G; Deloukas, Panos; Doherty, Michael; Engström, Gunnar; Helgadottir, Hafdis T; Hofman, Albert; Ingvarsson, Thorvaldur; Jonsson, Helgi; Keis, Aime; Keurentjes, J Christiaan; Kloppenburg, Margreet; Lind, Penelope A; McCaskie, Andrew; Martin, Nicholas G; Milani, Lili; Montgomery, Grant W; Nelissen, Rob G H H; Nevitt, Michael C; Nilsson, Peter M; Ollier, William ER; Parimi, Neeta; Rai, Ashok; Ralston, Stuart H; Reed, Mike R; Riancho, Jose A; Rivadeneira, Fernando; Rodriguez-Fontenla, Cristina; Southam, Lorraine; Thorsteinsdottir, Unnur; Tsezou, Aspasia; Wallis, Gillian A; Wilkinson, J Mark; Gonzalez, Antonio; Lane, Nancy E; Lohmander, L Stefan; Loughlin, John; Metspalu, Andres; Uitterlinden, Andre G; Jonsdottir, Ingileif; Stefansson, Kari; Slagboom, P Eline; Zeggini, Eleftheria; Meulenbelt, Ingrid; Ioannidis, John PA; Spector, Tim D; van Meurs, Joyce B J; Valdes, Ana M

    2014-01-01

    Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for ‘in silico’ or ‘de novo’ replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10−9 and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10−8) and follow-up studies (p=7.3×10−4). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10−7, OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10−6, OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS. PMID:23989986

  4. Association study of polymorphisms in synaptic vesicle-associated genes, SYN2 and CPLX2, with schizophrenia

    Directory of Open Access Journals (Sweden)

    Chung Joo-Ho

    2005-08-01

    Full Text Available Abstract Background The occurrence of aberrant functional connectivity in the neuronal circuit is one of the integrative theories of the etiology of schizophrenia. Previous studies have reported that the protein and mRNA levels of the synapsin 2 (SYN2 and complexin 2 (CPLX2 genes were decreased in patients with schizophrenia. Synapsin 2 and complexin 2 are involved in synaptogenesis and the modulation of neurotransmitter release. This report presents a study of the association of polymorphisms of SYN2 and CPLX2 with schizophrenia in the Korean population. Methods Six single nucleotide polymorphisms (SNPs and one 5-bp insertion/deletion in SYN2 and five SNPs in CPLX2 were genotyped in 154 Korean patients with schizophrenia and 133 control patients using direct sequencing or restriction fragment length polymorphism analysis. An intermarker linkage disequilibrium map was constructed for each gene. Results Although there was no significant difference in the genotypic distributions and allelic frequencies of either SYN2 or CPLX2 polymorphisms between the schizophrenia and control groups, the two-way haplotype analyses revealed significant associations with the disease (P SYN2 with schizophrenia (P Conclusion These results suggest that both SYN2 and CPLX2 may confer susceptibility to schizophrenia in the Korean population.

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

    Directory of Open Access Journals (Sweden)

    Kidambi Srividya

    2012-04-01

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

  6. Type 2 diabetes genetic association database manually curated for the study design and odds ratio

    Directory of Open Access Journals (Sweden)

    Park Hun

    2010-12-01

    Full Text Available Abstract Background The prevalence of type 2 diabetes has reached epidemic proportions worldwide, and the incidence of life-threatening complications of diabetes through continued exposure of tissues to high glucose levels is increasing. Advances in genotyping technology have increased the scale and accuracy of the genotype data so that an association genetic study has expanded enormously. Consequently, it is difficult to search the published association data efficiently, and several databases on the association results have been constructed, but these databases have their limitations to researchers: some providing only genome-wide association data, some not focused on the association but more on the integrative data, and some are not user-friendly. In this study, a user-friend database of type 2 diabetes genetic association of manually curated information was constructed. Description The list of publications used in this study was collected from the HuGE Navigator, which is an online database of published genome epidemiology literature. Because type 2 diabetes genetic association database (T2DGADB aims to provide specialized information on the genetic risk factors involved in the development of type 2 diabetes, 701 of the 1,771 publications in the type 2 Diabetes case-control study for the development of the disease were extracted. Conclusions In the database, the association results were grouped as either positive or negative. The gene and SNP names were replaced with gene symbols and rsSNP numbers, the association p-values were determined manually, and the results are displayed by graphs and tables. In addition, the study design in publications, such as the population type and size are described. This database can be used for research purposes, such as an association and functional study of type 2 diabetes related genes, and as a primary genetic resource to construct a diabetes risk test in the preparation of personalized medicine in the

  7. Individual and Environmental Characteristics Associated with Cognitive Development in Down Syndrome: A Longitudinal Study

    Science.gov (United States)

    Couzens, Donna; Haynes, Michele; Cuskelly, Monica

    2012-01-01

    Background: Associations among cognitive development and intrapersonal and environmental characteristics were investigated for 89 longitudinal study participants with Down syndrome to understand developmental patterns associated with cognitive strengths and weaknesses. Materials and Methods: Subtest scores of the Stanford-Binet IV collected…

  8. The association between adolescents’ health and disparities in school career: a longitudinal cohort study.

    NARCIS (Netherlands)

    Uiters, E.; Maurits, E.; Droomers, M.; Zwaanswijk, M.; Verheij, R.A.; Lucht, F. van der

    2014-01-01

    Background: Literature suggests that children’s educational achievement is associated with their health status and the socioeconomic position of their parents. Few studies have investigated this association in adolescence, while this is an important period affecting future life trajectories. Our

  9. Is problem-based learning associated with students’ motivation? A quantitative and qualitative study

    NARCIS (Netherlands)

    M. Wijnen (Marit); S.M.M. Loyens (Sofie); L. Wijnia (Lisette); G. Smeets (Guus); M.J. Kroeze (Maarten); H.T. van der Molen (Henk)

    2017-01-01

    textabstractIn this study, a mixed-method design was employed to investigate the association between a student-centred, problem-based learning (PBL) method and law students’ motivation. Self-determination theory (SDT) states that autonomous motivation, which is associated with higher academic

  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. Genome-wide association studies in economics and entrepreneurship research: promises and limitations

    NARCIS (Netherlands)

    Ph.D. Koellinger (Philipp); M.J.H.M. van der Loos (Matthijs); P.J.F. Groenen (Patrick); A.R. Thurik (Roy); F. Rivadeneira Ramirez (Fernando); F.J.A. van Rooij (Frank)

    2010-01-01

    textabstractThe recently developed genome-wide association study (GWAS) design enables the identification of genes specifically associated with economic outcomes such as occupational and other choices. This is a promising new approach for economics research which we aim to apply to the choice for

  12. Genome-wide association studies in economics and entrepreneurship research: Promises and limitations

    NARCIS (Netherlands)

    Ph.D. Koellinger (Philipp); M.J.H.M. van der Loos (Matthijs); P.J.F. Groenen (Patrick); A.R. Thurik (Roy); F. Rivadeneira Ramirez (Fernando); F.J.A. van Rooij (Frank); A.G. Uitterlinden (André); A. Hofman (Albert)

    2010-01-01

    textabstractThe recently developed genome-wide association study (GWAS) design enables the identification of genes specifically associated with economic outcomes such as occupational and other choices. This is a promising new approach for economics research which we aim to apply to the choice for

  13. Genome-Wide Association Study of Intelligence: Additive Effects of Novel Brain Expressed Genes

    Science.gov (United States)

    Loo, Sandra K.; Shtir, Corina; Doyle, Alysa E.; Mick, Eric; McGough, James J.; McCracken, James; Biederman, Joseph; Smalley, Susan L.; Cantor, Rita M.; Faraone, Stephen V.; Nelson, Stanley F.

    2012-01-01

    Objective: The purpose of the present study was to identify common genetic variants that are associated with human intelligence or general cognitive ability. Method: We performed a genome-wide association analysis with a dense set of 1 million single-nucleotide polymorphisms (SNPs) and quantitative intelligence scores within an ancestrally…

  14. The association between neighborhood disorder, social cohesion and hazardous alcohol use: A national multilevel study

    NARCIS (Netherlands)

    Kuipers, Mirte A. G.; van Poppel, Mireille N. M.; van den Brink, Wim; Wingen, Marleen; Kunst, Anton E.

    2012-01-01

    Background: Evidence on associations of alcohol use with neighborhood disorder and social cohesion is limited. The aim of this study was to further investigate these associations. Methods: Individual data of 14,258 Dutch adults, living in 1546 neighborhoods across the Netherlands, were obtained from

  15. Genome-wide association study implicates PARD3B-based AIDS restriction

    NARCIS (Netherlands)

    Troyer, Jennifer L.; Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Li, Guan; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

    2011-01-01

    Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. European

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

    Science.gov (United States)

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

    2012-01-01

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

  17. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and

  18. Gene-based association studies report genetic links for clinical subtypes of frontotemporal dementia

    NARCIS (Netherlands)

    Mishra, Aniket; Ferrari, Raffaele; Heutink, Peter; Hardy, John; Pijnenburg, Yolande; Posthuma, Danielle

    2017-01-01

    Genome-wide association studies in frontotemporal dementia showed limited success in identifying associated loci. This is possibly due to small sample size, allelic heterogeneity, small effect sizes of single genetic variants, and the necessity to statistically correct for testing millions of

  19. 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 ast...

  20. Genome-wide association study of kidney function decline in individuals of European descent

    NARCIS (Netherlands)

    M. Gorski (Mathias); A. Tin (Adrienne); M. Garnaas (Maija); G.M. McMahon (Gearoid M.); A.Y. Chu (Audrey Y.); B. Tayo (Bamidele); C. Pattaro (Cristian); A. Teumer (Alexander); D.I. Chasman (Daniel); J. Chalmers (John); P. Hamet (Pavel); J. Tremblay (Johanne); M. Woodward (Mark); T. Aspelund (Thor); G. Eiriksdottir (Gudny); V. Gudnason (Vilmundur); T.B. Harris (Tamara); L.J. Launer (Lenore); A.V. Smith (Albert V.); B.D. Mitchell (Braxton); J.R. O´Connell; A.R. Shuldiner (Alan); J. Coresh (Josef); M. Li (Man); P. Freudenberger (Paul); E. Hofer (Edith); R. Schmidt (Reinhold); R. Schmidt (Reinhold); E.G. Holliday (Elizabeth); P. Mitchell (Paul); J.J. Wang (Jie Jin); I.H. de Boer (Ian); G. Li (Guo); D.S. Siscovick (David); Z. Kutalik; T. Corre (Tanguy); P. Vollenweider (Peter); G. Waeber (Gérard); J. Gupta (Jayanta); P.P. Kanetsky (Peter P.); S.J. Hwang; M. Olden (Matthias); Q. Yang (Qiong Fang); M. de Andrade (Mariza); E.J. Atkinson (Elizabeth J.); S.L.R. Kardia (Sharon); S.T. Turner (Stephen); J.M. Stafford (Jeanette M.); J. Ding (Jinhui); Y. Liu; C. Barlassina (Christina); D. Cusi (Daniele); E. Salvi (Erika); J.A. Staessen (Jan); P.M. Ridker (Paul); H. Grallert (Harald); C. Meisinger (Christa); M. Müller-Nurasyid (Martina); B.K. Krämer (Bernhard K.); H. Kramer (Holly); S.E. Rosas (Sylvia E.); I.M. Nolte (Ilja M.); B.W.J.H. Penninx (Brenda); H. Snieder (Harold); M. Fabiola Del Greco; A. Franke (Andre); U. Nöthlings (Ute); W. Lieb (Wolfgang); S.J.L. Bakker (Stephan); R.T. Gansevoort (Ron); P. Van Der Harst (Pim); A. Dehghan (Abbas); O.H. Franco (Oscar); A. Hofman (Albert); F. Rivadeneira Ramirez (Fernando); S. Sedaghat (Sanaz); A.G. Uitterlinden (André); S. Coassin (Stefan); M. Haun (Margot); B. Kollerits (Barbara); F. Kronenberg (Florian); B. Paulweber (Bernhard); N. Aumann (Nicole); K. Endlich (Karlhans); M. Pietzner (Mike); U. Völker (Uwe); R. Rettig (Rainer); V. Chouraki (Vincent); C. Helmer (Catherine); J.-C. Lambert (Jean-Charles); M. Metzger (Marie); B. Stengel (Benedicte); T. Lehtimäki (Terho); L.-P. Lyytikäinen (Leo-Pekka); O. Raitakari (Olli); A.D. Johnson (Andrew); A. Parsa (Afshin); M. Bochud (Murielle); I.M. Heid (Iris); W. Goessling (Wolfram); A. K̈ttgen (Anna); W.H.L. Kao (Wen); C.S. Fox (Caroline S.); C.A. Böger (Carsten)

    2015-01-01

    textabstractGenome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially

  1. Genome-wide association study of kidney function decline in individuals of European descent

    NARCIS (Netherlands)

    Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M.; Chu, Audrey Y.; Tayo, Bamidele O.; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I.; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tamara B.; Launer, Lenore J.; Smith, Albert V.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G.; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H.; Li, Guo; Siscovick, David S.; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gerard; Gupta, Jayanta; Kanetsky, Peter A.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J.; Kardia, Sharon L. R.; Turner, Stephen T.; Stafford, Jeanette M.; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A.; Ridker, Paul M.; Grallert, Harald; Meisinger, Christa; Mueller-Nurasyid, Martina; Kraemer, Bernhard K.; Kramer, Holly; Rosas, Sylvia E.; Nolte, Ilja M.; Penninx, Brenda W.; Snieder, Harold; Del Greco, M. Fabiola; Franke, Andre; Noethlings, Ute; Lieb, Wolfgang; Bakker, Stephan J. L.; Gansevoort, Ron T.; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, Andre G.; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Voelker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimaki, Terho; Lyytikainen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Kottgen, Anna; Kao, W. H. Linda; Fox, Caroline S.; Boeger, Carsten A.

    Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16

  2. Association between Lifestyle and School Attendance in Japanese Medical Students: A Pilot Study

    Science.gov (United States)

    Tanaka, Masaaki; Watanabe, Yasuyoshi

    2012-01-01

    Objective: Lifestyle factors are thought to be associated with students' academic performance. Whether lifestyle factors were associated with medical students' school attendance was determined. Design: Cross-sectional design. Setting: The study group consisted of 157 healthy second-year medical students attending Osaka City University Graduate…

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  4. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study

    NARCIS (Netherlands)

    J.B. Richards (Brent); F. Rivadeneira Ramirez (Fernando); M. Inouye (Michael); T. Pastinen; N. Soranzo (Nicole); S.G. Wilson (Scott); T. Andrew (Toby); M. Falchi (Mario); R. Gwilliam (Rhian); K.R. Ahmadi (Kourosh); A.M. Valdes; P.P. Arp (Pascal); P. Whittaker; D.J. Verlaan (Dominique); M. Jhamai (Mila); V. Kumanduri; M.J. Moorhouse (Michael); J.B.J. van Meurs (Joyce); A. Hofman (Albert); H.A.P. Pols (Huib); D.J. Hart; G. Zhai (Guangju); B.S. Kato; B.H. Mullin (Benjamin); F. Zhang (Feng); P. Deloukas (Panagiotis); A.G. Uitterlinden (André); T.D. Spector (Timothy)

    2008-01-01

    textabstractBackground: Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density. Methods: In this genome-wide association study, we identified the most

  5. Meta-analysis of Genome-Wide Association Studies for Extraversion

    DEFF Research Database (Denmark)

    van den Berg, Stéphanie M; de Moor, Marleen H M; Verweij, K. J. H.

    2016-01-01

    Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively ...

  6. School, Neighborhood, and Family Factors Are Associated with Children's Bullying Involvement: A Nationally Representative Longitudinal Study

    Science.gov (United States)

    Bowes, Lucy; Arseneault, Louise; Maughan, Barbara; Taylor, Alan; Caspi, Ashalom; Moffitt, Terrie E.

    2009-01-01

    School size and problems with neighbors is associated with a greater risk of being a bullying victim while family factors such as maltreatment and domestic violence are associated with involvement in bullying. The findings are based on the Environmental Risk Longitudinal Twin Study that involves 2,232 children.

  7. Unique associations among emotion dysregulation dimensions and aggressive tendencies : A multi-site study

    NARCIS (Netherlands)

    Velotti, Patrizia; Casselman, Robert B.; Garofalo, C.; McKenzie, Melissa D.

    2017-01-01

    While problems with emotion regulation (ER) have long been associated with internalizing symptoms, only recently has an ER framework been applied to the study of aggression. Therefore, little is known about the unique and independent associations between specific domains of the ER construct and

  8. Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma

    NARCIS (Netherlands)

    Luykx, J. J.; Bakker, S. C.; Visser, W. F.; Verhoeven-Duif, N.; Buizer-Voskamp, J. E.; den Heijer, J. M.; Boks, M. P M; Sul, J. H.; Eskin, E.; Ori, A. P.; Cantor, R. M.; Vorstman, J.; Strengman, E.; DeYoung, J.; Kappen, T. H.; Pariama, E.; van Dongen, E. P A; Borgdorff, P.; Bruins, P.; de Koning, T. J.; Kahn, R. S.; Ophoff, R. A.

    2015-01-01