TY - JOUR T1 - A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts JF - bioRxiv DO - 10.1101/083030 SP - 083030 AU - Sara Lindström AU - Stephanie Loomis AU - Constance Turman AU - Hongyan Huang AU - Jinyan Huang AU - Hugues Aschard AU - Andrew T. Chan AU - Hyon Choi AU - Marilyn Cornelis AU - Gary Curhan AU - Immaculata De Vivo AU - A. Heather Eliassen AU - Charles Fuchs AU - Michael Gaziano AU - Susan E. Hankinson AU - Frank Hu AU - Majken Jensen AU - Jae H. Kang AU - Christopher Kabrhel AU - Liming Liang AU - Louis R. Pasquale AU - Eric Rimm AU - Meir J. Stampfer AU - Rulla M. Tamimi AU - Shelley S. Tworoger AU - Janey L. Wiggs AU - David J. Hunter AU - Peter Kraft Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/10/25/083030.abstract N2 - The Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)).We observed the strongest BMI association for the FTO SNP rs55872725 (β=0.45, p=3.48×10−22), and using a significance level of p=0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR=2.17, 95% CI: 1.79-2.63, p=2.70×10−15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes. ER -