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

Abstract

Aims 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 (GWAS) 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. Methods 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. Results An increase in genetic risk score was significantly associated with higher levels of coronary artery calcified plaque (p=1.23 × 10−4); however, no significant associations with self-reported myocardial infarction and CVD events and all-cause and CVD mortality were observed. Conclusions 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.

Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial

“…In 2011, Qi et al (19) reported that a GRS based on five CAD loci from the general population was significantly associated with prevalent or incident CAD among subjects with type 2 diabetes. Similarly, in the Diabetes Heart Study, a GRS based on 28 CAD loci was associated with history of cardiovascular disease and with levels of coronary artery calcification (31). More recently, a GRS based on 153 SNPs associated with CAD at genome-wide significant levels or surviving a 5% false discovery rate in the general population (8) was found to be significantly associated with incident cardiovascular events (including stroke) in the Look AHEAD trial (32).…”

Association of common gene variants in glucokinase regulatory protein with cardiorenal disease: A systematic review and meta-analysis

“…The genetic variants of interest were often not reported in the main article, but could be found in the (online) supplementary materials of the article. For one GWAS, the authors were contacted and the requested data were kindly provided [ 25 ].…”

“…Of note, these effect sizes were not statistically different (p = 0.36). Repeat analysis without the study with low quality [ 25 ] (i.e. NOS score <5 stars) did not affect the primary outcome.…”

Genetic Risk Score for Coronary Heart Disease: Review

“…In subsequent years (2008–2015), studies had been carried out with different variations of the GRS and indicated correlations with CHD, MI, or other CVDs ( Table S1 ) [ 4 , 5 , 6 , 7 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Nonetheless, several studies have not detected such an association ( Table S1 ) [ 41 , 42 , 43 ].…”