全基因组关联研究
冠状动脉疾病
遗传关联
单核苷酸多态性
医学
内科学
连锁不平衡
基因分型
心肌梗塞
人口
遗传力
遗传学
生物
基因
基因型
环境卫生
作者
Salma M. Wakil,Ram Ramesh,Nzioka P. Muiya,Munish Mehta,Editha Andres,Nejat Mazhar,Batoul Baz,Samya Hagos,Maie Alshahid,Brian F. Meyer,Grant Morahan,Nduna Dzimiri
标识
DOI:10.1016/j.atherosclerosis.2015.11.019
摘要
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.
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