Impact of Genetics on Coronary Heart Disease, Low-Density Lipoprotein Cholesterol Levels and Control

Hypercholesterolemia is a prevalent risk factor for coronary heart disease (CHD) which is a leading cause of death among Hispanics/Latinos. Rates of cholesterol awareness and treatment are low in this population. Genetic risk scores (GRS) have been used in populations of European ancestry to identify those at higher risk for CHD events. The purpose of this study was to apply two previously constructed GRS, 1) to assess their association with prevalent and incident CHD, and low-density lipoprotein (LDL) cholesterol levels in a diverse cohort of Hispanics/Latinos 2) to evaluate the association of the GRS with LDL control among statin users, and 3) to evaluate whether GRS improves prediction of CHD over traditional risk factors. We utilized baseline and longitudinal data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective study that enrolled 16,415 Hispanic/Latino adults aged 18-74 years from four U.S. communities between 2008-2011. The two GRS were found to be associated with prevalent and incident CHD, and LDL cholesterol levels, respectively; however, when stratified by genetic admixture, associations were more robust among participants with higher proportions of European ancestry. The predictive value of traditional risk factors was improved when combined with the GRS for CHD. The GRS associated with LDL was positively associated with LDL levels. Among participants taking statins, those at highest genetic risk had the lowest odds of LDL control. The results highlight the need for additional studies to evaluate and optimize risk prediction using cumulative genetic risk in a diverse Hispanic/Latino population. These findings support the development of Hispanic/Latino-specific GRS for early life risk prediction, mitigation of CHD events and LDL control. Importantly, this study is among the first to investigate GRS associated with CHD, LDL levels, and LDL control within a Hispanic/Latino population and helps to address the dearth of genetic data for an underrepresented population. As precision medicine enters clinical practice, the overall results of this study have implications for prevention of widening health disparities among Hispanics/Latinos living in the U.S and for advocating for population diversity in genetic research.