Genetic Risk Score for Coronary Heart Disease in the Hispanic/Latino Population

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PROJECT SUMMARY/ABSTRACT Coronary heart disease (CHD) is one of the leading causes of death for the Hispanic/Latino population living in the United States (U.S.). The rates of CHD in the Hispanic/Latino community are similar to the non-Hispanic white population; however, risk factors for CHD among Hispanics/Latinos are more prevalent. As the largest and expanding minority group in the U.S., Hispanics/Latinos face a disparate burden of CHD risk, especially as the population ages. Within the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), hypercholesterolemia is the most prevalent risk factor for CHD among Hispanic/Latino men and the second most common among women. In addition, levels of awareness, treatment, and control of high cholesterol in this population are very low. One way to reduce the burden of CHD is to target therapy and primary prevention in high-risk groups. A genetic risk score (GRS) has been used in European ancestry populations to identify those at higher risk for CHD events and who would benefit most from statin therapy. Unfortunately, genetic research to date has predominantly been conducted in populations of European ancestry, creating a disparity in this area of study. While many phenotype-genotype associations have generalized across populations, the portability of a GRS derived from a European ancestry population may be suboptimal due to differences in linkage disequilibrium, allele frequencies, and genetic architecture; nonetheless, it has been shown that selecting genetic variants from the robust genome-wide association study (GWAS) literature in European ancestry populations generally performs well in a Hispanic/Latino population and begins to address gaps in knowledge of genetic risk among understudied populations. The purpose of this study is to utilize a previously constructed GRS, using weights derived from a multiethnic cohort analysis that included a small subset of Latinos, to assess its association with incident CHD in the HCHS/SOL cohort, to evaluate the association of the GRS with incident CHD among statin users, and to evaluate whether the GRS improves prediction of CHD over traditional risk factors or whether traditional risk factors mediate the relationship between the GRS and CHD. The overall results have implications for lessening health disparities among Hispanics/Latinos living in the U.S. and advocating for diverse populations in genetic research. The activities incorporated into this proposal (study design, advanced statistics, quantitative/computational approaches, and presentation of findings) cover the set of fundamental research skills required by a scientist entering the interdisciplinary field of genetic epidemiology in the era of Precision Public Health. The applied experience gained from carrying out this research, combined with didactic training and individual mentoring, comprises a comprehensive research training plan that will serve as a platform to launch my career as an independent investigator in genetic epidemiology.