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

TitleLarge-scale association analysis identifies new risk loci for coronary artery disease.
Publication TypeJournal Article
Year of Publication2013
AuthorsDeloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, Ingelsson E, Saleheen D, Erdmann J, Goldstein BA et al.
Corporate AuthorsCARDIoGRAMplusC4D Consortium, DIAGRAM Consortium, Cardiogenics Consortium, MuTHER Consortium, Wellcome Trust Case Control Consortium
JournalNat Genet
Volume45
Issue1
Pagination25-33
Date Published2013 Jan
ISSN1546-1718
KeywordsAdult, Aged, Asian Continental Ancestry Group, Cell Line, Coronary Artery Disease, European Continental Ancestry Group, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors
Abstract

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.

DOI10.1038/ng.2480
Alternate JournalNat. Genet.
PubMed ID23202125