Genetic Variants Identified in a European Genome-Wide Association Study That Were Found to Predict Incident Coronary Heart Disease in the Atherosclerosis Risk in Communities Study
Genetic Variants Identified in a European Genome-Wide Association Study That Were Found to Predict Incident Coronary Heart Disease in the Atherosclerosis Risk in Communities Study
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DOI：
10.1093/aje/kwp377
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发表时间：
2010-01-01
影响因子：
5
通讯作者：
Boerwinkle, Eric
中科院分区：
文献类型：
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作者：
Bressler, Jan;Folsom, Aaron R.;Boerwinkle, Eric
2007年，Wellcome Trust Case Control Consortium（WTCCC）对2，000例英国冠心病（CHD）病例和3，000例对照进行了全基因组关联研究，对469，557个单核苷酸多态性（SNP）进行了基因分型。最初确定了7个与CHD相关的变异，随后在重复研究中发现了5个SNP。在目前的研究中，作者的目的是确定WTCCC报告的12个SNP是否预测了一项双向前瞻性队列研究（社区动脉粥样硬化风险）中2004年的冠心病事件，该研究包括15，792名45-64岁的人，这些人是在1987-1989年从4个不同的美国社区通过概率抽样选出的。在加性遗传模型下，使用校正了年龄和性别的考克斯比例风险模型来估计17年期间（白人1,362例，非洲裔美国人397例）的CHD风险率比（HRR）。结果显示，白人中有3个SNP（rs 599839、rs 1333049和rs 501120; HRR分别为1.10（P = 0.044）、1.14在非裔美国人中，1个SNP（rs7250581; HRR = 1.60，P = 0.05）与CHD事件显著相关。这项研究表明，在一项病例对照全基因组关联研究中发现的遗传变异可能在一般人群中CHD的遗传病因学中发挥作用。
In 2007, the Wellcome Trust Case Control Consortium (WTCCC) performed a genome-wide association study in 2,000 British coronary heart disease (CHD) cases and 3,000 controls after genotyping 469,557 single nucleotide polymorphisms (SNPs). Seven variants associated with CHD were initially identified, and 5 SNPs were later found in replication studies. In the current study, the authors aimed to determine whether the 12 SNPs reported by the WTCCC predicted incident CHD through 2004 in a biracial, prospective cohort study (Atherosclerosis Risk in Communities) comprising 15,792 persons aged 45-64 years who had been selected by probability sampling from 4 different US communities in 1987-1989. Cox proportional hazards models with adjustment for age and gender were used to estimate CHD hazard rate ratios (HRRs) over a 17-year period (1,362 cases in whites and 397 cases in African Americans) under an additive genetic model. The results showed that 3 SNPs in whites (rs599839, rs1333049, and rs501120; HRRs were 1.10 (P = 0.044), 1.14 (P < 0.001), and 1.14 (P = 0.030), respectively) and 1 SNP in African Americans (rs7250581; HRR = 1.60, P = 0.05) were significantly associated with incident CHD. This study demonstrates that genetic variants revealed in a case-control genome-wide association study enriched for early disease onset may play a role in the genetic etiology of CHD in the general population.