Abstract 4113: Genetic Risk of Coronary Heart Disease in the Atherosclerosis Risk in Communities (ARIC) study: Application of a Genetic Risk Score
Background- We asked if a genetic risk score (GRS) that aggregates the risk of CHD associated with five gene variants could predict risk of CHD. These were variants of VAMP8, KIF6, SNX19, PALLD, and MYH15, and the risk alleles of these variants were associated with CHD in two antecedent association studies and in the white participants of Atherosclerosis Risk in Communities (ARIC).
Methods- We combined the risk of five gene variants to create a GRS by giving equal weight to each SNP and each risk allele. The hazard ratio (HR) for incident CHD for those with a high GRS (4% of those in ARIC) compared to those without a high GRS was estimated for 13 years of follow-up in ARIC by Cox proportional hazards models that adjusted for traditional risk factors.
Results- The HR for a high GRS was 1.57 (95% CI 1.21 to 2.04) in whites (n=9389) and 1.34 (95% CI 0.63 to 2.86) in blacks (n=3167). Among the white ARIC participants without diabetes, those with a high GRS had a HR of 1.76 (95% CI 1.33 to 2.32) and those with diabetes had a HR of 0.86 (95% CI 0.40 to 1.84; P=0.095 for diabetes by high GRS interaction). Among those without a family history of CHD, those with a high GRS had a HR of 1.88 (95% CI 1.40–2.53) and those with a family history for CHD had a HR of 1.06 (95% CI 0.62–1.82; P=0.089 for family history by high GRS interaction). Among those with a high GRS who had neither diabetes nor family history, the HR was 2.01 (95% CI 1.46–2.77) for whites and 1.98 (95% CI 0.87– 4.52) for blacks. Among the white ARIC participants when traditional risk factors and the GRS were dichotomized and analyzed together in a Cox model, the adjusted HR for a high GRS was in the same range as the HR of traditional risk factors: the HRs were 1.44 for family history, 1.45 for HDL-C <40mg/dL, 1.57 for a high GRS, 1.60 for smoking, 1.63 for hypertension, 1.74 for LDL-C ≥130mg/dL, and 2.67 for diabetes (all P<0.001).
Conclusions- After adjustment for traditional risk factors, a high GRS predicted risk of CHD in whites, and a similar trend was observed in the black participants of ARIC. The risk estimates for the high GRS was similar in magnitude to those of some traditional risk factors (HDL-C, age, smoking, hypertension, LDL-C).