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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.* ; Surendran, P.* ; Mälarstig, A.* ; Wilk, J.B.* ; Tybjaerg-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.E.* ; Reiner, A.P.* ; Buyske, S.* ; Hindorff, L.A.* ; Carty, C.L.* ; North, K.E.* ; Kooperberg, C.* ; Boerwinkle, E.* ; Young, K.L.* ; Graff, M.* ; Peters, U.* ; Absher, D.* ; Hsiung, C.A.* ; Lee, W.* ; Taylor, K.D.* ; Chen, Y.* ; Lee, I.* ; Guo, X.* ; Chung, R.H.* ; Hung, Y.-J.* ; Rotter, J.I.* ; Juang, J.J.* ; Quertermous, T.* ; Wang, T.* ; Rasheed, A.* ; Frossard, P.* ; Alam, D.S.* ; Majumder, A.a.S.* ; di Angelantonio, E.* ; Chowdhury, R.* ; Chen, Y.I.* ; Nørdestgaard, B.G.* ; Assimes, T.L.* ; Danesh, J.* ; Butterworth, A.S.* ; Saleheen, D.* ; CARDIoGRAMplusC4D Consortium (Meisinger, C. ; Peters, A. ; Müller-Nurasyid, M.)

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

Nat. Genet. 49, 1113-1119 (2017)
Postprint DOI PMC
Open Access Green
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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
Journal Nature Genetics
Quellenangaben Volume: 49, Issue: 7, Pages: 1113-1119 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Independent Research Group Clinical Epidemiology (KEPI)
Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)