Liu Robin, Cheng Jiahui, Muzlera Carlos, Robinson John F, Ban Matthew R, Hegele Robert A
Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
University of Waterloo, Waterloo, Ontario, Canada.
CJC Open. 2019 Mar 29;1(2):69-75. doi: 10.1016/j.cjco.2019.01.003. eCollection 2019 Mar.
Coronary artery disease (CAD) risk traditionally has been assessed using clinical risk factors. We evaluated whether molecular genetic markers for CAD risk could add information to traditional variables.
We developed a false discovery rate 267-marker genetic risk score (FDR) from markers that were significantly associated with CAD in the UK Biobank cohort meta-analysis. FDR was tested in the Atherosclerosis Risk in Communities cohort using logistic regression and Cox proportional hazards analyses in the European and African American groups.
Our genetic risk score (FDR) was associated with a 1.45 (95% confidence interval, 1.39-1.51) increase in odds ratio and a 1.32 (95% confidence interval, 1.26-1.38) increase in hazard ratio per standard deviation of the score. The score modestly improved the area under the curve (AUC) statistic when added to a clinical model (ΔAUC = 0.0112, = 0.0002). FDR predicted incident CAD (C-index = 0.60), although it did not improve on clinical risk factors (ΔAUC = 0.0159, = 0.0965). Individuals in the top quintile of FDR genetic risk were at approximately 2-fold increased risk compared with the bottom quintile, which is comparable to risk associated with self-reported family history. The performance of FDR was less robust in the African American sample.
FDR is significantly associated with CAD in the European sample, with an effect size comparable to self-reported family history. FDR discriminated between individuals with and without CAD, but did not improve CAD risk prediction over clinical variables. FDR was less predictive of CAD risk in African Americans.
传统上，冠心病（CAD）风险是通过临床风险因素进行评估的。我们评估了CAD风险的分子遗传标记是否能为传统变量增添信息。
我们从英国生物银行队列荟萃分析中与CAD显著相关的标记物开发了一个错误发现率为267个标记物的遗传风险评分（FDR）。在社区动脉粥样硬化风险队列中，使用逻辑回归和Cox比例风险分析在欧洲裔和非裔美国人组中对FDR进行了测试。
我们的遗传风险评分（FDR）与每标准差评分的比值比增加1.45（95%置信区间，1.39 - 1.51）以及风险比增加1.32（95%置信区间，1.26 - 1.38）相关。当将该评分添加到临床模型中时，适度提高了曲线下面积（AUC）统计量（ΔAUC = 0.0112，P = 0.0002）。FDR预测了CAD的发病（C指数 = 0.60），尽管它在临床风险因素方面没有改善（ΔAUC = 0.0159，P = 0.0965）。FDR遗传风险最高五分位数的个体与最低五分位数相比，风险增加约2倍，这与自我报告的家族史相关风险相当。FDR在非裔美国人样本中的表现不太稳健。
FDR在欧洲样本中与CAD显著相关，效应大小与自我报告的家族史相当。FDR区分了有CAD和无CAD的个体，但在CAD风险预测方面没有比临床变量有所改善。FDR对非裔美国人CAD风险的预测性较低。
