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

项目摘要/摘要 冠心病(CHD)是居住在中国的拉美裔/拉丁裔人口的主要死亡原因之一 美国(美国)。拉美裔/拉丁裔社区的冠心病发病率与非拉美裔相似 然而，拉美裔/拉丁裔人群中的冠心病风险因素更为普遍。作为最大和最大的 在美国不断扩大的少数群体中，拉美裔/拉丁裔面临着不同的冠心病风险负担，特别是在 人口老龄化。在西班牙裔社区健康研究/拉丁裔研究(HCHS/SOL)范围内， 在拉美裔/拉丁裔男性中，高胆固醇血症是冠心病最常见的危险因素，其次是 在女性中很常见。此外，人们对高胆固醇的认识、治疗和控制水平 人口非常少。减轻冠心病负担的方法之一是有针对性地治疗和一级预防 高危人群。遗传风险评分(GRS)已经在欧洲血统人群中被用来识别 发生冠心病事件的风险更高，谁将从他汀类药物治疗中受益最多。不幸的是，基因研究 到目前为止，主要是在欧洲血统的人群中进行，造成了这一地区的差异 在学习方面。虽然许多表型-基因型关联已经在人群中推广，但 由于连锁的差异，来自欧洲血统群体的GRS可能是次优的 不平衡、等位基因频率和遗传结构；然而，已经表明选择基因 欧洲血统人群中的健壮全基因组关联研究(GWAS)文献的变体 通常在西班牙裔/拉丁裔人群中表现良好，并开始解决遗传风险知识方面的差距 在研究不足的人群中。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裔，以评估其 与HCHS/SOL队列中发生的CHD的关联，以评估GRS与事件的关联 他汀类药物使用者中的冠心病，并评估GRS是否比传统风险更能改善对冠心病的预测 或传统危险因素是否在GRS与CHD之间的关系中起中介作用。总的结果 对缩小居住在美国的拉美裔/拉美裔之间的健康差距并倡导 基因研究中的不同群体。本建议书中包含的活动(研究设计，高级 统计、定量/计算方法和调查结果的陈述)涵盖了一套基本的 进入遗传流行病学跨学科领域的科学家应具备的研究技能 精准公共卫生。结合教学，开展本研究的应用经验 培训和个人指导，包括将作为平台的全面研究培训计划 开始我的职业生涯，成为一名遗传流行病学的独立研究员。

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.