Genetic risk score associations with cardiovascular disease and mortality in the Diabetes Heart Study.

Cox AJ, Hsu FC, Ng MC, Langefeld CD, Freedman BI, Carr JJ, Bowden DW
Diabetes Care. 2014 37 (4): 1157-64

PMID: 24574349 · PMCID: PMC4178326 · DOI:10.2337/dc13-1514

OBJECTIVE Given the high rates of cardiovascular disease (CVD) and associated mortality in individuals with type 2 diabetes, identifying and understanding predictors of CVD events and mortality could help inform clinical management in this high-risk group. Recent large-scale genetic studies may provide additional tools in this regard. RESEARCH DESIGN AND METHODS Genetic risk scores (GRSs) were constructed in 1,175 self-identified European American (EA) individuals comprising the family-based Diabetes Heart Study based on 1) 13 single nucleotide polymorphisms (SNPs) and 2) 30 SNPs with previously documented associations with CVD in genome-wide association studies. Associations between each GRS and a self-reported history of CVD, coronary artery calcified plaque (CAC) determined by noncontrast computed tomography scan, all-cause mortality, and CVD mortality were examined using marginal models with generalized estimating equations and Cox proportional hazards models. RESULTS The weighted 13-SNP GRS was associated with prior CVD (odds ratio [OR] 1.51 [95% CI 1.22-1.86]; P = 0.0002), CAC (β-coefficient [β] 0.22 [0.02-0.43]; P = 0.04) and CVD mortality (hazard ratio [HR] 1.35 [1.10-1.81]; P = 0.04) when adjusting for the other known CVD risk factors: age, sex, type 2 diabetes affection status, BMI, current smoking status, hypertension, and dyslipidemia. The weighted 30-SNP GRS was also associated with prior CVD (OR 1.33 [1.08-1.65]; P = 0.008), CAC (β 0.29 [0.08-0.50]; P = 0.006), all-cause mortality (HR 1.28 [1.05-1.56]; P = 0.01), and CVD mortality (HR 1.46 [1.08-1.96]; P = 0.01). CONCLUSIONS These findings support the utility of two simple GRSs in examining genetic associations for adverse outcomes in EAs with type 2 diabetes.

MeSH Terms (16)

Aged Coronary Artery Disease Diabetes Mellitus, Type 2 European Continental Ancestry Group Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Middle Aged Odds Ratio Plaque, Atherosclerotic Polymorphism, Single Nucleotide Proportional Hazards Models Risk Factors Tomography, X-Ray Computed

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