title: Genetic risk score associations with cardiovascular disease and mortality in the Diabetes Heart Study.
abstract: 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.
authors.affiliation: Corresponding author: Donald W. Bowden, dbowden@wakehealth.edu.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cox
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics* / Q000401:mortality*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000401:mortality*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D044465:White People