Analysis of a cardiovascular disease genetic risk score in the Diabetes Heart Study

It remains unclear whether the high cardiovascular disease (CVD) burden in people with type 2 diabetes (T2D) is associated with genetic variants that contribute to CVD in general populations. Recent studies have examined genetic risk scores of single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies for their cumulative contribution to CVD-related traits. Most analyses combined SNPs associated with a single phenotypic class, e.g., lipids. In the present analysis, we examined a more comprehensive risk score comprised of SNPs associated with a broad range of CVD risk phenotypes. The composite risk score was analyzed for potential associations with subclinical CVD, self-reported CVD events, and mortality in 983 T2D-affected individuals of European descent from 466 Diabetes Heart Study (DHS) families. Genetic association was examined using marginal models with generalized estimating equations for subclinical CVD and prior CVD events and Cox proportional hazards models with sandwich-based variance estimation for mortality; analyses were adjusted for age and sex. An increase in genetic risk score was significantly associated with higher levels of coronary artery calcified plaque (p = 1.23 x 10(-4)); however, no significant associations with self-reported myocardial infarction and CVD events and all-cause and CVD mortality were observed. These results suggest that a genetic risk score of SNPs associated with CVD events and risk factors does not significantly account for CVD risk in the DHS, highlighting the limitations of applying current genetic markers for CVD in individuals with diabetes.