RT Journal Article
SR Electronic
T1 A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 083030
DO 10.1101/083030
A1 Sara Lindström
A1 Stephanie Loomis
A1 Constance Turman
A1 Hongyan Huang
A1 Jinyan Huang
A1 Hugues Aschard
A1 Andrew T. Chan
A1 Hyon Choi
A1 Marilyn Cornelis
A1 Gary Curhan
A1 Immaculata De Vivo
A1 A. Heather Eliassen
A1 Charles Fuchs
A1 Michael Gaziano
A1 Susan E. Hankinson
A1 Frank Hu
A1 Majken Jensen
A1 Jae H. Kang
A1 Christopher Kabrhel
A1 Liming Liang
A1 Louis R. Pasquale
A1 Eric Rimm
A1 Meir J. Stampfer
A1 Rulla M. Tamimi
A1 Shelley S. Tworoger
A1 Janey L. Wiggs
A1 David J. Hunter
A1 Peter Kraft
YR 2016
UL http://biorxiv.org/content/early/2016/10/25/083030.abstract
AB 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.