RT Journal Article
SR Electronic
T1 Meta-analysis of genome-wide association studies for height and body mass index in ∼700,000 individuals of European ancestry
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 274654
DO 10.1101/274654
A1 Loic Yengo
A1 Julia Sidorenko
A1 Kathryn E. Kemper
A1 Zhili Zheng
A1 Andrew R. Wood
A1 Michael N. Weedon
A1 Timothy M. Frayling
A1 Joel Hirschhorn
A1 Jian Yang
A1 Peter M. Visscher
A1 the GIANT Consortium
YR 2018
UL http://biorxiv.org/content/early/2018/03/22/274654.abstract
AB Genome-wide association studies (GWAS) stand as powerful experimental designs for identifying DNA variants associated with complex traits and diseases. In the past decade, both the number of such studies and their sample sizes have increased dramatically. Recent GWAS of height and body mass index (BMI) in ∼250,000 European participants have led to the discovery of ∼700 and ∼100 nearly independent SNPs associated with these traits, respectively. Here we combine summary statistics from those two studies with GWAS of height and BMI performed in ∼450,000 UK Biobank participants of European ancestry. Overall, our combined GWAS meta-analysis reaches N∼700,000 individuals and substantially increases the number of GWAS signals associated with these traits. We identified 3,290 and 716 near-independent SNPs associated with height and BMI, respectively (at a revised genome-wide significance threshold of p<1 × 10−8), including 1,185 height-associated SNPs and 554 BMI-associated SNPs located within loci not previously identified by these two GWAS. The genome-wide significant SNPs explain ∼24.6% of the variance of height and ∼5% of the variance of BMI in an independent sample from the Health and Retirement Study (HRS). Correlations between polygenic scores based upon these SNPs with actual height and BMI in HRS participants were 0.44 and 0.20, respectively. From analyses of integrating GWAS and eQTL data by Summary-data based Mendelian Randomization (SMR), we identified an enrichment of eQTLs amongst lead height and BMI signals, prioritisting 684 and 134 genes, respectively. Our study demonstrates that, as previously predicted, increasing GWAS sample sizes continues to deliver, by discovery of new loci, increasing prediction accuracy and providing additional data to achieve deeper insight into complex trait biology. All summary statistics are made available for follow up studies.