Abstract P554: Association of a Genetic Risk Score With Cholesterol and Cholesterol Control: Findings From the Hispanic Community Heath Study/Study of Latinos

Background: Hypercholesterolemia is a prevalent cardiovascular (CVD) risk factor among Hispanics/Latinos; however, rates of cholesterol awareness and treatment are low in this population. Using a genetic risk score (GRS) associated with low-density lipoprotein cholesterol (LDL) levels may help identify those who would benefit most from statin therapy. A 223-SNP GRS was previously shown to be associated with baseline LDL levels and CVD risk in European, African, and East Asian populations, but it was not evaluated for use in a Hispanic/Latino population. Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective study that enrolled 16,415 Hispanic/Latino adults aged 18-74 years from four US communities in 2008-2011. We assessed the association of a 223-SNP GRS with baseline LDL levels and cholesterol control among 8,868 HCHS/SOL participants with complete data and consent to conduct genetic research. A weighted GRS was calculated using effect sizes estimated from the Million Veteran Program Genome Wide Association Study that included about 25,000 Hispanic/Latino participants. Multivariable linear regression analysis was used to derive effect size estimates (Betas (β), 95% confidence intervals (CI)) for the association between the GRS, modeled continuously and by quintiles, and LDL levels. Multivariable logistic regression was used to derive odds ratios and 95% CI for the association between GRS and LDL control in statin users. LDL control was defined as LDL <130mg/dL or <100 mg/dL in those with diabetes. Models were adjusted for predefined confounders and accounted for survey weights. Results: For each standard deviation increase in GRS, LDL levels increased on average by 8.61mg/dL (95% CI 7.37, 9.83) when adjusted by age, sex, and the first 5 principal components. GRS associations with LDL differed by strata of sex, Hispanic/Latino background group, and European genetic ancestry proportion. In 1,114 statin users, odds of cholesterol control were 38% less likely for those in the highest quintile of GRS compared to the lowest quintile, although not significant (OR 0.62, 95% CI 0.36, 1.08). Conclusion: The 223-SNP GRS shows promise to identify those who are more likely to develop higher LDL and may benefit most from statin therapy in a Hispanic/Latino population. However, additional studies are needed in a larger population of Hispanic/Latino statin users for confirmation of these results.