Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10-8) 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; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 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.

Original publication

DOI

10.1038/ng.3913

Type

Journal article

Journal

Nature genetics

Publication Date

09/2017

Volume

49

Pages

1385 - 1391

Addresses

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Keywords

EPIC-CVD Consortium, CARDIoGRAMplusC4D, UK Biobank CardioMetabolic Consortium CHD working group, Humans, Genetic Predisposition to Disease, Risk Factors, Reproducibility of Results, Genotype, Phenotype, Polymorphism, Single Nucleotide, Coronary Artery Disease, Meta-Analysis as Topic, Genome-Wide Association Study, Genetic Loci, Genetic Association Studies, Health Information Systems, United Kingdom