Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Diabetes Care. 2022 Mar 1;45(3):734-741. doi: 10.2337/dc21-0974.
Individuals with type 1 diabetes are at a high lifetime risk of coronary artery disease (CAD), calling for early interventions. This study explores the use of a genetic risk score (GRS) for CAD risk prediction, compares it to established clinical markers, and investigates its performance according to the age and pharmacological treatment.
This study in 3,295 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study (467 incident CAD, 14.8 years follow-up) used three risk scores: a GRS, a validated clinical score, and their combined score. Hazard ratios (HR) were calculated with Cox regression, and model performances were compared with the Harrell C-index (C-index).
A HR of 6.7 for CAD was observed between the highest and the lowest 5th percentile of the GRS (P = 1.8 × 10-6). The performance of GRS (C-index = 0.562) was similar to HbA1c (C-index = 0.563, P = 0.96 for difference), HDL (C-index = 0.571, P = 0.6), and total cholesterol (C-index = 0.594, P = 0.1). The GRS was not correlated with the clinical score (r = -0.013, P = 0.5). The combined score outperformed the clinical score (C-index = 0.813 vs. C-index = 0.820, P = 0.003). The GRS performed better in individuals below the median age (38.6 years) compared with those above (C-index = 0.637 vs. C-index = 0.546).
A GRS identified individuals at high risk of CAD and worked better in younger individuals. GRS was also an independent risk factor for CAD, with a predictive power comparable to that of HbA1c and HDL and total cholesterol, and when incorporated into a clinical model, modestly improved the predictions. The GRS promises early risk stratification in clinical practice by enhancing the prediction of CAD.
1 型糖尿病患者终生患冠心病（CAD）的风险较高，因此需要早期干预。本研究探讨了使用 CAD 风险预测的遗传风险评分（GRS），将其与已建立的临床标志物进行比较，并根据年龄和药物治疗情况研究其性能。
这项在来自芬兰糖尿病肾病研究（3295 名参与者，其中 467 人发生 CAD，随访 14.8 年）中的研究使用了三种风险评分：GRS、经过验证的临床评分和它们的综合评分。使用 Cox 回归计算危险比（HR），并比较模型性能与 Harrell C 指数（C 指数）。
GRS 最高和最低 5%百分位数之间的 CAD 风险 HR 为 6.7（P=1.8×10-6）。GRS 的性能（C 指数=0.562）与 HbA1c（C 指数=0.563，P=0.96 用于差异）、HDL（C 指数=0.571，P=0.6）和总胆固醇（C 指数=0.594，P=0.1）相似。GRS 与临床评分无相关性（r=-0.013，P=0.5）。综合评分优于临床评分（C 指数=0.813 与 C 指数=0.820，P=0.003）。在中位数年龄（38.6 岁）以下的个体中，GRS 的表现优于年龄以上的个体（C 指数=0.637 与 C 指数=0.546）。
GRS 可识别 CAD 高危个体，在年轻个体中效果更好。GRS 也是 CAD 的独立危险因素，其预测能力与 HbA1c 和 HDL 及总胆固醇相当，并且当纳入临床模型时，可适度提高预测能力。GRS 通过增强 CAD 的预测，有望在临床实践中实现早期风险分层。
