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

Abstract

Genome-wide association studies (GWAS) in coronary artery disease (CAD) have identified 66 loci at ‘genome-wide significance’ (p < 5 × 10-8) but a much larger number of putative loci at a false discovery rate (FDR) of 5%1-4. 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 it (HARD; Ncases=6,482) and selected the former for conducting a meta-analysis with the two most recent CAD GWASs2-3. This approach identified 13 new loci at genome-wide significance, 12 of which were in our previous 5% FDR list2, and provided strong support that the remaining FDR loci represent genuine signals. The set of 304 independent variants at 5% FDR in this study explain 21.2% of CAD heritability and identified 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.

Metadata

Item Type:	Article
Authors/Creators:	Nelson, CP Goel, A Butterworth, A Kanoni, S Webb, TR Marouli, E Zeng, L Ntalla, I Lai, FY Hopewell, JC Giannakopoulou, O Jiang, T Hamby, SE Angelantonio, ED Assimes, TL Bottinger, EP Chambers, JC Clarke, R Palmer, C Cubbon, RM https://orcid.org/0000-0001-7844-3600 Ellinor, P Ermel, R Evangelou, E Franks, PW Grace, C Gu, D Hingorani, AD Howson, JMM Ingelsson, E Kastrati, A Kessler, T Kyriakou, T Lehtimaki, T Lu, X Lu, Y Marz, W McPherson, R Metspalu, A Pujades Rodriguez, MDM https://orcid.org/0000-0002-1375-1028 Ruusalepp, A Schadt, EE Schmidt, AF Sweeting, MJ Zalloua, PA AIGhalayini, 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 CARDIoGRAMplusC4D The UK Biobank CardioMetabolic Consortium CHD working group Schunkert, H Farrall, M Danesh, J Samani, NL Watkins, H Deloukas, P
Copyright, Publisher and Additional Information:	© 2017 Nature America, Inc., part of Springer Nature. This is an author produced version of a paper published in Nature Genetics. Uploaded in accordance with the publisher's self-archiving policy.
Keywords:	Cardiovascular diseases; Genetics; Genome-wide association studies; Sequence annotation
Dates:	Published: 1 September 2017 Published (online): 17 July 2017 Accepted: 15 June 2017
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Health Sciences (Leeds) > Centre for Health Services Research (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	25 May 2017 12:45
Last Modified:	29 Jan 2021 11:53
Status:	Published
Publisher:	Nature Publishing Group
Identification Number:	10.1038/ng.3913
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:116865

CORE (COnnecting REpositories)

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

Abstract

Metadata

Download

Accepted Version

Export

Statistics