A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs. (February 2016)

• Record Type: Journal Article
• Authors: Wakil, Salma M.; Ram, Ramesh; Muiya, Nzioka P.; Mehta, Munish; Andres, Editha; Mazhar, Nejat; Baz, Batoul; Hagos, Samya; Alshahid, Maie; Meyer, Brian F.; Morahan, Grant; Dzimiri, Nduna
• Is Part Of: Atherosclerosis. Volume 245(2016)
• Page Start: 62
• Page End: 70
• Publication Date: 2016-02
• Subjects: Genome-wide association -- Myocardial infarction -- Coronary artery disease -- Haplotypes -- Heritability -- CDKN2A/B -- CXCL12 -- KCNE2; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.11.019
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background: Multiple loci have been identified for coronary artery disease (CAD) by genome-wide association studies (GWAS), but no such studies on CAD incidence has been reported yet for any Middle Eastern population. Methods: In this study, we performed a GWAS for CAD and myocardial infarction (MI) incidence in 5668 Saudis of Arab descent using the Affymetrix Axiom Genotyping platform. Results: We describe SNPs at 16 loci that showed significant (P < 5 × 10 −8 ) or suggestive GWAS association (P < 1 × 10 −5 ) with CAD or MI, in the ethnic Saudi Arab population. Among the four variants reaching GWAS significance in the present study, the rs10738607_G [0.78(0.71–0.85); p = 2.17E-08] in CDNK2A/B gene was associated with CAD. Two other SNPs on the same gene, rs10757274_G [0.79(0.73–0.86); p = 2.98E-08] and rs1333045_C [0.79(0.73–0.86); p = 1.15E-08] as well as the rs9982601_T [1.38(1.23–1.55); p = 3.49E-08] on KCNE2 were associated with MI. These variants have been previously described in other populations. Several SNPs, including the rs7421388 ( PLCL1) and rs12541758 ( TRPA1) displaying a suggestive GWAS association (P < 1 × 10 −5 ) with CAD as well as rs41411047 ( RNF13 ), rs32793 ( PDZD2 ) and rs4739066 ( YTHDF3 ), similarly showing weak association with MI, were confirmed in an independent dataset. Furthermore, our estimation of heritability of CAD and MI based on observed genome-wide sharing in unrelated Saudi Arabs was approximately 33% and 44%, respectively. Conclusions: Our study has identified susceptibility variants for CAD/MI in ethnic Arabs. These findings provide further insights into pathways contributing to the susceptibility for CAD and will enable more comprehensive genetic studies of these diseases in Middle East populations. Highlights: We performed GWAS for CAD/MI in 5431 Saudi Arabs by the Affymetrix Axiom Genotyping platform. We discovered SNPs in 14 loci conferring risk for CAD/MI. Results on 6 of these SNPs were replicated in an independent dataset. Our heritability estimations for CAD/MI were approximately 33% and 44%, respectively. Our study identified several susceptibility variants as well as currently unfamiliar genes for CAD/MI in ethnic Arabs.