Association analyses based on false discovery rate implicate new loci for coronary artery disease
UK Biobank CardioMetabolic Consortium CHD working group,
Nature Publishing Group
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Nelson, C., Goel, A., Butterworth, A., Kanoni, S., Webb, T., Marouli, E., Zeng, L., et al. (2017). Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nature Genetics https://doi.org/10.1038/ng.3913
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.
cardiovascular diseases, genetics, genome-wide association studies, sequence annotation
For funding information please visit the publisher's website.
British Heart Foundation (RG/08/014/24067)
External DOI: https://doi.org/10.1038/ng.3913
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266676