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

Nelson, CP; Goel, A; Butterworth, AS; Kanoni, S; Webb, TR; Marouli, E; Zeng, L; ... Deloukas, P; + view all (2017) Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nature Genetics , 49 (9) pp. 1385-1391. 10.1038/ng.3913. Green open access

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Abstract

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 GWAS2,3. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold2, 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.

Type: Article
Title: Association analyses based on false discovery rate implicate new loci for coronary artery disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ng.3913
Publisher version: http://dx.doi.org/10.1038/ng.3913
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: GENOME-WIDE ASSOCIATION, GENETIC-VARIANTS, LOW-FREQUENCY, RISK LOCI, ATHEROSCLEROSIS, METAANALYSIS, ANNOTATION, PROFILES, DATABASE, RARE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/1567161
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