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Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms.

Nat. Genet. 49, 1113-1119 (2017)
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide1,2. Although 58 genomic regions have been associated with CAD thus far3-9, most of the heritability is unexplained9, 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 metaanalysis 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 x 10(-8), in fixed-effects meta-analysis) 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 celltype- specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gene-expression; Genomewide Association; Protein-c; Chromatin States; Plasma-levels; Trans-eqtls; Variants; Metaanalysis; Haptoglobin; Mortality
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Zeitschrift Nature Genetics
Quellenangaben Band: 49, Heft: 7, Seiten: 1113-1119 Artikelnummer: , Supplement: ,
Verlag Nature America
Verlagsort New York, NY