Large-scale association analysis identifies new risk loci for coronary artery disease

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 &...

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Main Authors: Deloukas, P, Kanoni, S, Willenborg, C, Farrall, M, Assimes, T, Thompson, JR, Ingelsson, E, Saleheen, D, Erdmann, J, Goldstein, B, Stirrups, K, König, I, Cazier, J, Johansson, A, Hall, A, Lee, J, Willer, C, Chambers, J, Esko, T, Folkersen, L
Formato: Journal article
Publicado em: 2013
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author Deloukas, P
Kanoni, S
Willenborg, C
Farrall, M
Farrall, M
Assimes, T
Thompson, JR
Ingelsson, E
Saleheen, D
Saleheen, D
Saleheen, D
Erdmann, J
Goldstein, B
Stirrups, K
König, I
Cazier, J
Johansson, A
Hall, A
Lee, J
Willer, C
Willer, C
Chambers, J
Esko, T
Esko, T
Folkersen, L
author_facet Deloukas, P
Kanoni, S
Willenborg, C
Farrall, M
Farrall, M
Assimes, T
Thompson, JR
Ingelsson, E
Saleheen, D
Saleheen, D
Saleheen, D
Erdmann, J
Goldstein, B
Stirrups, K
König, I
Cazier, J
Johansson, A
Hall, A
Lee, J
Willer, C
Willer, C
Chambers, J
Esko, T
Esko, T
Folkersen, L
author_sort Deloukas, P
collection OXFORD
description Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. © 2013 Nature America, Inc. All rights reserved.
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spelling oxford-uuid:9a737e1a-1350-4ad5-ab0b-086e6bb351bc2022-03-27T00:21:25ZLarge-scale association analysis identifies new risk loci for coronary artery diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9a737e1a-1350-4ad5-ab0b-086e6bb351bcSymplectic Elements at Oxford2013Deloukas, PKanoni, SWillenborg, CFarrall, MFarrall, MAssimes, TThompson, JRIngelsson, ESaleheen, DSaleheen, DSaleheen, DErdmann, JGoldstein, BStirrups, KKönig, ICazier, JJohansson, AHall, ALee, JWiller, CWiller, CChambers, JEsko, TEsko, TFolkersen, LCoronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. © 2013 Nature America, Inc. All rights reserved.
spellingShingle Deloukas, P
Kanoni, S
Willenborg, C
Farrall, M
Farrall, M
Assimes, T
Thompson, JR
Ingelsson, E
Saleheen, D
Saleheen, D
Saleheen, D
Erdmann, J
Goldstein, B
Stirrups, K
König, I
Cazier, J
Johansson, A
Hall, A
Lee, J
Willer, C
Willer, C
Chambers, J
Esko, T
Esko, T
Folkersen, L
Large-scale association analysis identifies new risk loci for coronary artery disease
title Large-scale association analysis identifies new risk loci for coronary artery disease
title_full Large-scale association analysis identifies new risk loci for coronary artery disease
title_fullStr Large-scale association analysis identifies new risk loci for coronary artery disease
title_full_unstemmed Large-scale association analysis identifies new risk loci for coronary artery disease
title_short Large-scale association analysis identifies new risk loci for coronary artery disease
title_sort large scale association analysis identifies new risk loci for coronary artery disease
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