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

Joanna M. M. Howson, Wei Zhao, Daniel R Barnes, Weang Kee Ho, Robin Young, Dirk S Paul, Lindsay Waite, Daniel F Freitag, Eric B Fauman, Elias L Salfati, Benjamin B Sun, John D Eicher, Andrew D Johnson, Wayne H-H Sheu, Sune F Nielsen, Wei-Yu Lin, Praveen Surendran, Anders Malarstig, Jemma B Wilk, Anne Tybjærg-HansenKatrine L Rasmussen, Pia R Kamstrup, Panos Deloukas, Jeanette Erdmann, Sekar Kathiresan, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, CARDIoGRAMplusC4D, Ron Do, Daniel J Rader, Julie A Johnson, Stanley L Hazen, Arshed A Quyyumi, John A Spertus, Carl J Pepine, Nora Franceschini, Anne E Justice, Alex P Reiner, Steven Buyske, Lucia A Hindorff, Cara L Carty, Kari E North, Charles Kooperberg, Eric Boerwinkle, Kristin L Young, Mariaelisa Graff, Ulrike Peters, Devin Absher, Chao A Hsiung, EPIC-CVD Consortium, Børge G Nordestgaard, Themistocles L Assimes, J Danesh, Adam S Butterworth, D Saleheen

Publikation: Bidrag til tidsskriftLetterForskningpeer review

232 Citationer (Scopus)

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-analysis 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-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 cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind49
Sider (fra-til)1113-1119
ISSN1061-4036
DOI
StatusUdgivet - 2017

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