Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms
Journal
Nature Genetics
Journal Volume
49
Journal Issue
7
Pages
1113-1119
Date Issued
2017
Author(s)
Howson J.M.M.
Zhao W.
Barnes D.R.
Ho W.-K.
Young R.
Paul D.S.
Waite L.L.
Freitag D.F.
Fauman E.B.
Salfati E.L.
Sun B.B.
Eicher J.D.
Johnson A.D.
Sheu W.H.H.
Nielsen S.F.
Lin W.-Y.
Surendran P.
Malarstig A.
Wilk J.B.
Tybjærg-Hansen A.
Rasmussen K.L.
Kamstrup P.R.
Deloukas P.
Erdmann J.
Kathiresan S.
Samani N.J.
Schunkert H.
Watkins H.
Do R.
Rader D.J.
Johnson J.A.
Hazen S.L.
Quyyumi A.A.
Spertus J.A.
Pepine C.J.
Franceschini N.
Justice A.
Reiner A.P.
Buyske S.
Hindorff L.A.
Carty C.L.
North K.E.
Kooperberg C.
Boerwinkle E.
Young K.
Graff M.
Peters U.
Absher D.
Hsiung C.A.
Lee W.-J.
Taylor K.D.
Chen Y.-H.
Lee I.-T.
Guo X.
Chung R.-H.
Hung Y.-J.
Rotter J.I.
Quertermous T.
Rasheed A.
Frossard P.
Alam D.S.
Majumder A.A.S.
Di Angelantonio E.
Chowdhury R.
Chen Y.-D.I.
Nordestgaard Bø.G.
Assimes T.L.
Danesh J.
Butterworth A.S.
Saleheen D.
CARDIoGRAMplusC4D, EPIC-CVD
Abstract
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta- A nalysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10-8, in fixed-effects meta- A nalysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms. ? 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
SDGs
Other Subjects
CD31 antigen; COL4A1 protein; COL4A2 protein; CXCL12 protein; endothelial protein C receptor; LMOD1 protein; PECAM1 protein; PHACTR1 protein; protein; protein C; unclassified drug; artery wall; Article; atherosclerosis; atherosclerotic plaque; cell adhesion; coronary artery disease; gene expression; gene frequency; gene linkage disequilibrium; gene locus; genetic variability; genome-wide association study; genomics; genotype; human; leukocyte migration; phenotype; priority journal; quantitative trait locus; single nucleotide polymorphism; artery; coronary artery disease; energy metabolism; female; genetic predisposition; genetics; genome-wide association study; histone code; male; meta analysis; neutrophil chemotaxis; pathology; pathophysiology; risk factor; vascular smooth muscle; Arteries; Atherosclerosis; Cell Adhesion; Chemotaxis, Leukocyte; Coronary Artery Disease; Energy Metabolism; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Histone Code; Humans; Male; Muscle, Smooth, Vascular; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Risk Factors
Publisher
Nature Publishing Group
Type
journal article