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Title: Association analyses based on false discovery rate implicate new loci for coronary artery disease
Authors: Nelson, Christopher P.
Goel, A
Butterworth, AS
Kanoni, S
Webb, Tom R.
Marouli, E
Zeng, L
Ntalla, I
Lai, Florence Y.
Hopewell, JC
Giannakopoulou, O
Jiang, T
Hamby, Stephen E.
Di Angelantonio, E
Assimes, TL
Bottinger, EP
Chambers, JC
Clarke, R
Palmer, CNA
Cubbon, RM
Ellinor, P
Ermel, R
Evangelou, E
Franks, PW
Grace, C
Gu, D
Hingorani, AD
Howson, JMM
Ingelsson, E
Kastrati, A
Kessler, T
Kyriakou, T
Lehtimäki, T
Lu, X
Lu, Y
März, W
McPherson, R
Metspalu, A
Pujades-Rodriguez, M
Ruusalepp, A
Schadt, EE
Schmidt, AF
Sweeting, MJ
Zalloua, PA
AlGhalayini, K
Keavney, BD
Kooner, JS
Loos, RJF
Patel, RS
Rutter, MK
Tomaszewski, M
Tzoulaki, I
Zeggini, E
Erdmann, J
Dedoussis, G
Björkegren, JLM
EPIC-CVD Consortium
UK Biobank CardioMetabolic Consortium CHD working group
Schunkert, H
Farrall, M
Danesh, J
Samani, Nilesh J.
Watkins, H
Deloukas, P
First Published: 17-Jul-2017
Publisher: Nature Publishing Group
Citation: Nature Genetics, 2017, 49 (9), pp. 1385-1391
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 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.
DOI Link: 10.1038/ng.3913
ISSN: 1061-4036
eISSN: 1546-1718
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2017, Nature Publishing Group. Deposited with reference to the publisher’s open access archiving policy.
Description: The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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