| Literature DB >> 28530674 |
Joanna M M Howson1, Wei Zhao2, Daniel R Barnes1, Weang-Kee Ho1,3, Robin Young1,4, Dirk S Paul1, Lindsay L Waite5, Daniel F Freitag1, Eric B Fauman6, Elias L Salfati7,8, Benjamin B Sun1, John D Eicher9,10, Andrew D Johnson9,10, Wayne H H Sheu11,12,13, Sune F Nielsen14, Wei-Yu Lin1,15, Praveen Surendran1, Anders Malarstig16, Jemma B Wilk17, Anne Tybjærg-Hansen18,19, Katrine L Rasmussen14, Pia R Kamstrup14, Panos Deloukas20,21, Jeanette Erdmann22,23,24, Sekar Kathiresan25,26, Nilesh J Samani27,28, Heribert Schunkert29,30, Hugh Watkins31,32, Ron Do33, Daniel J Rader34, Julie A Johnson35, Stanley L Hazen36, Arshed A Quyyumi37, John A Spertus38,39, Carl J Pepine40, Nora Franceschini41, Anne Justice41, Alex P Reiner42, Steven Buyske43, Lucia A Hindorff44, Cara L Carty45, Kari E North41,46, Charles Kooperberg45, Eric Boerwinkle47,48, Kristin Young41, Mariaelisa Graff41, Ulrike Peters45, Devin Absher5, Chao A Hsiung49, Wen-Jane Lee50, Kent D Taylor51, Ying-Hsiang Chen49, I-Te Lee52, Xiuqing Guo51, Ren-Hua Chung49, Yi-Jen Hung13,53, Jerome I Rotter54, Jyh-Ming J Juang55,56, Thomas Quertermous7,8, Tzung-Dau Wang55,56, Asif Rasheed57, Philippe Frossard57, Dewan S Alam58, Abdulla Al Shafi Majumder59, Emanuele Di Angelantonio1,60, Rajiv Chowdhury1, Yii-Der Ida Chen51, Børge G Nordestgaard14,19, Themistocles L Assimes7,8, John Danesh1,60,61,62, Adam S Butterworth1,60, Danish Saleheen1,2,57.
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.Entities:
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Year: 2017 PMID： 28530674 PMCID： PMC5555387 DOI： 10.1038/ng.3874
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307