Five common gene variants identify elevated genetic risk for coronary heart disease
Five common gene variants identify elevated genetic risk for coronary heart disease
复制标题
DOI：
10.1097/gim.0b013e318156fb62
复制
发表时间：
2007-10-01
影响因子：
8.8
通讯作者：
Boerwinkle, Eric
中科院分区：
文献类型：
--
作者：
Bare, Lance A.;Morrison, Alanna C.;Boerwinkle, Eric
目的：由于多种遗传变异影响冠心病的风险，我们将几项研究中与冠心病相关的多种变异合并为遗传风险评分，并询问在考虑传统风险因素后，高遗传风险评分是否与冠心病显著相关。研究方法：我们在两项研究中考虑了与冠心病相关的五种变异，并在社区动脉粥样硬化风险研究中得到证实：rs 20455（KIF 6），rs3900940（MYH 15），rs7439293（PALLD），rs 2298566（SNX 19）和rs 1010（VAMP 8）。我们计算了社区研究参与者中每个动脉粥样硬化风险的遗传风险评分，并在考克斯模型中估计了高遗传风险评分（与不高相比）的冠心病事件的风险比，该模型在中位数为13年的随访中调整了传统的风险因素。结果如下：对于具有高遗传风险评分的白色参与者（9129名白人中的4%），与没有高遗传风险评分的参与者相比，冠心病事件的风险比为1.57（95%置信区间1.21-2.04; P = 0.001）。使用自助样本进行的内部验证估计，在外部人群中，预期风险比为1.43。结论：在调整传统的风险因素后，在社区动脉粥样硬化风险研究中，那些遗传风险评分高的人患冠心病的风险增加了57%。
Purpose: Because multiple genetic variants influence risk for coronary heart disease, we combined multiple variants that had been associated with coronary heart disease in several studies into a genetic risk score and asked whether a high genetic risk score would be significantly associated with coronary heart disease after accounting for traditional risk factors. Methods: We considered five variants that were associated with coronary heart disease in two studies and confirmed in the Atherosclerosis Risk in Communities study: rs20455 (KIF6), rs3900940 (MYH15), rs7439293 (PALLD), rs2298566 (SNX19), and rs1010 (VAMP8). We calculated a genetic risk score for each Atherosclerosis Risk in Communities study participant and estimated the hazard ratio for incident coronary heart disease of a high genetic risk score (compared with not-high) in Cox models that adjusted for traditional risk factors during a median of 13 years of follow-up. Results: For white participants with a high genetic risk score (4% of the 9129 whites), compared with those without a high genetic risk score, the hazard ratio for incident coronary heart disease was 1.57 (95% confidence interval 1.21-2.04; P = 0.001). Internal validation using bootstrap samples estimated that a hazard ratio of 1.43 could be expected in external populations. Conclusions: After adjusting for traditional risk factors, those with a high genetic risk score had a 57% increased risk of incident coronary heart disease in the Atherosclerosis Risk in Communities study.