Association analyses based on false discovery rate implicate new loci for coronary artery disease.

Nat Genet
Authors
Keywords
Abstract

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P 5 × 10) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n = 10,801) as well as a stricter definition without angina (HARD; n = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.

Year of Publication
2017
Journal
Nat Genet
Volume
49
Issue
9
Pages
1385-1391
Date Published
2017 Sep
ISSN
1546-1718
DOI
10.1038/ng.3913
PubMed ID
28714975
Links
Grant list
G0800270 / Medical Research Council / United Kingdom
MC_QA137853 / Medical Research Council / United Kingdom
G0700931 / Medical Research Council / United Kingdom
RG/08/014/24067 / British Heart Foundation / United Kingdom
PG/12/32/29544 / British Heart Foundation / United Kingdom
MR/L003120/1 / Medical Research Council / United Kingdom
S10 OD018522 / OD / NIH HHS / United States
G0601966 / Medical Research Council / United Kingdom
RG/14/5/30893 / British Heart Foundation / United Kingdom
FS/12/80/29821 / British Heart Foundation / United Kingdom
FS/14/76/30933 / British Heart Foundation / United Kingdom
RG/10/12/28456 / British Heart Foundation / United Kingdom