Prediction of Coronary Heart Disease Risk using a Genetic Risk Score: The Atherosclerosis Risk in Communities Study

TLDR

Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary heart disease prediction models. This US study aggregated multiple single nucleotide polymorphisms into a genetic risk score and tested whether adding the score to traditional risk factors improves CHD prediction. The ARIC cohort was followed for a median of 13 years; participants were genotyped for 116 CHD‑associated SNPs, and SNPs nominally predicting incident CHD were included in the genetic risk score. The genetic risk score was significantly associated with incident CHD in both Blacks and Whites and improved the area under the ROC curve for Blacks and suggested improvement for Whites, demonstrating that aggregating SNPs can enhance CHD risk prediction.

Abstract

Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary heart disease (CHD) prediction models. This 1986–2001 US study aggregated the contribution of multiple single nucleotide polymorphisms into a genetic risk score (GRS) and assessed whether the GRS plus traditional risk factors predict CHD better than traditional risk factors alone. The Atherosclerosis Risk in Communities (ARIC) cohort was followed for a median of 13 years for CHD events (n = 1,452). Individuals were genotyped for 116 single nucleotide polymorphisms associated with CHD in multiple case-control studies. Single nucleotide polymorphisms nominally predicting incident CHD in the ARIC study were included in the GRS. The GRS was significantly associated with incident CHD in Blacks (hazard rate ratio = 1.20, 95% confidence interval: 1.11, 1.29) and Whites (hazard rate ratio = 1.10, 95% confidence interval: 1.06, 1.14) as well as in each tertile defined by the traditional cardiovascular risk score (p ≤ 0.02). When receiver operating characteristic curves based on traditional risk factors were recalculated after the GRS was added, the increase in the area under the receiver operating characteristic curve was statistically significant for Blacks and suggestive of improved CHD prediction for Whites. This study demonstrates the concept of aggregating information from multiple single nucleotide polymorphisms into a risk score and indicates that it can improve prediction of incident CHD in the ARIC study.