Genetic Risk Score Enhances Coronary Artery Disease Risk Prediction in Individuals With Type 1 Diabetes
RESEARCH DESIGN AND METHODS This study in 3,295 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study (467 incident CAD, 14.8 years follow-up) employed three risk scores: a GRS, a validated clinical score and their combined score. Hazard ratios (HR) were calculated with Cox regression and model performances compared with Harrel’s C-index.
RESULTS 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 [C] 0.562) was similar to HbA1c (C=0.563, p-value for difference 0.96), HDL (C=0.571, P=0.6) and total cholesterol (C=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=0.813 vs C=0.820, P=0.003). The GRS performed better in individuals below the median age (38.6 years) compared to those above (C=0.637 vs C=0.546).
CONCLUSIONS 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, 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.