Background:Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS improves prediction beyond modifiable risk factors in this population is not known.Methods:Genotyped adults aged 18 to 35 years were selected from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=1132) and FOS (Framingham Offspring Study; n=663). Systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, triglycerides, smoking, and waist circumference or body mass index were measured at the visit 1 exam of each study, and coronary artery calcium, a measure of coronary atherosclerosis, was assessed at year 15 (CARDIA) or year 30 (FOS). A previously validated PRS for coronary heart disease was computed for each subject. The C statistic and integrated discrimination improvement were used to compare improvements in prediction of elevated coronary artery calcium between models containing the PRS, risk factors, or both.Results:There were 62 (5%) and 93 (14%) participants with a coronary artery calcium score >20 (CARDIA) and >300 (FOS), respectively. At these thresholds, the C statistic changes of adding the PRS to a risk factor–based model were 0.015 (0.004–0.028) and 0.020 (0.001–0.039) in CARDIA and FOS, respectively. When adding risk factors to a PRS-based model, the respective changes were 0.070 (0.033–0.109) and 0.051 (0.017–0.079). The integrated discrimination improvement, when adding the PRS to a risk factor model, was 0.027 (−0.006 to 0.054) in CARDIA and 0.039 (0.0005–0.072) in FOS.Conclusions:Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.

中文翻译：

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多基因风险评分以识别年轻人的亚临床冠心病风险

背景：多基因风险评分 (PRS) 可以加强年轻人冠心病的风险分层。冠心病 PRS 是否能改善该人群中可改变的危险因素之外的预测尚不清楚。方法：从 CARDIA 研究（年轻成人冠状动脉风险发展；n=1132）和 FOS（弗雷明汉后代研究；n=663）。在每项研究的第 1 次访视检查中测量收缩压、总胆固醇和 HDL（高密度脂蛋白）胆固醇、甘油三酯、吸烟和腰围或体重指数，并评估冠状动脉钙（冠状动脉粥样硬化的测量指标）在 15 岁 (CARDIA) 或 30 岁 (FOS)。为每个受试者计算了先前验证的冠心病 PRS。C 统计和综合辨别改进用于比较包含 PRS、危险因素或两者的模型之间冠状动脉钙升高预测的改进。结果：有 62 (5%) 和 93 (14%) 名参与者患有冠状动脉动脉钙化评分分别 >20 (CARDIA) 和 >300 (FOS)。在这些阈值下，将 PRS 添加到基于风险因素的模型的 C 统计量变化在 CARDIA 和 FOS 中分别为 0.015 (0.004–0.028) 和 0.020 (0.001–0.039)。将风险因素添加到基于 PRS 的模型时，相应的变化分别为 0.070 (0.033–0.109) 和 0.051 (0.017–0.079)。将 PRS 添加到风险因素模型时，CARDIA 的综合辨别力改善为 0.027（-0.006 至 0.054），FOS 为 0.039（0.0005-0.072）。结论：在年轻人中，