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

项目总结/摘要 冠心病（CHD）是生活在美国的西班牙裔/拉丁裔人口的主要死亡原因之一。 美国（U.S.）。西班牙裔/拉丁裔社区的CHD发病率与非西班牙裔社区相似。 白色人群;然而，西班牙裔/拉丁裔人群中CHD的风险因素更为普遍。作为最大的， 美国少数族裔群体的扩大，西班牙裔/拉丁裔面临着不同的冠心病风险负担，特别是 人口老龄化。在西班牙裔社区健康研究/拉丁裔研究（HCHS/SOL）中， 高胆固醇血症是西班牙裔/拉丁裔男性中冠心病最常见的危险因素， 常见于女性。此外，认识水平，治疗，并控制高胆固醇在这方面 人口非常低。减少冠心病负担的一种方法是在患者中进行靶向治疗和一级预防。 高危人群。遗传风险评分（GRS）已被用于欧洲血统人群，以确定那些 冠心病事件的风险较高，并且从他汀类药物治疗中获益最多。不幸的是，基因研究 迄今为止，主要在欧洲血统的人群中进行，在这一领域造成了差异 学习。虽然许多表型-基因型关联在人群中普遍存在，但 来自欧洲血统人群的GRS可能由于连锁的差异而不是最佳的 不平衡，等位基因频率和遗传结构;尽管如此，已经表明，选择遗传 来自欧洲血统人群的稳健全基因组关联研究（GWAS）文献的变异 在西班牙裔/拉丁裔人群中通常表现良好，并开始解决遗传风险知识方面的差距 在未被充分研究的人群中本研究的目的是利用先前构建的GRS，使用 权重来自多种族队列分析，其中包括一小部分拉丁美洲人，以评估其 与HCHS/SOL队列中CHD事件的相关性，以评价GRS与CHD事件的相关性 他汀类药物使用者中的CHD，并评估GRS是否比传统风险改善了CHD的预测 因素或传统危险因素是否介导GRS和CHD之间的关系。总体结果 对减少生活在美国的西班牙裔/拉丁裔之间的健康差距有影响，并倡导 基因研究中的不同人群。纳入本提案的活动（研究设计，高级 统计，定量/计算方法，并介绍调查结果）涵盖了一套基本的 研究技能所需的科学家进入遗传流行病学的跨学科领域的时代， 精准公共卫生。从开展这项研究中获得的应用经验，结合教学 培训和个人辅导，包括一个全面的研究培训计划，将作为一个平台， 作为一名独立的遗传流行病学调查员开始我的职业生涯。

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.