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

西班牙裔/拉丁裔人群冠心病的遗传风险评分

• 批准号: 10311902
• 负责人: Christina G Hutten
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311902
• 关键词: Address; Adult; Advocate; Age; Area; Awareness; Catalogs; Cause of Death; Cessation of life; Cholesterol; Classification; Cohort Analysis; Communities; Consent; Coronary heart disease; Diabetes Mellitus; Disease Outcome; Environmental Risk Factor; European; Event; Face; Gene Frequency; General Population; Genetic; Genetic Research; Genetic Risk; Genotype; Goals; Healthcare; High Prevalence; Hispanic Community Health Study/Study of Latinos; Hispanics; Hypertension; Individual; Investigation; Knowledge; LDL Cholesterol Lipoproteins; Latino; Linkage Disequilibrium; Literature; Measures; Mediating; Mediation; Mediator of activation protein; Mentors; Minority Groups; National Human Genome Research Institute; Not Hispanic or Latino; Obesity; Participant; Pharmaceutical Preparations; Phenotype; Population; Population Heterogeneity; Precision Medicine Initiative; Primary Prevention; Public Health; Relative Risks; Research; Research Design; Research Personnel; Research Training; Risk; Risk Factors; Risk Reduction; Sampling; Sampling Studies; Scientist; Smoking; Training; Underrepresented Populations; United States; Weight; Woman; base; career; cohort; coronary event; experience; fundamental research; genetic architecture; genetic association; genetic epidemiology; genetic information; genetic variant; genome wide association study; health data; health disparity; heart disease risk; high risk; high risk population; hypercholesterolemia; improved; indexing; innovation; men; mortality; multi-ethnic; portability; precision medicine; response; skills; statistics; targeted treatment

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.

项目概要/摘要 冠心病 (CHD) 是居住在西班牙裔/拉丁裔人口的主要原因之一 美国（U.S.）。西班牙裔/拉丁裔社区的冠心病发病率与非西班牙裔社区相似 白人人口；然而，西班牙裔/拉丁裔中冠心病的危险因素更为普遍。作为最大和 随着美国少数民族群体的不断扩大，西班牙裔/拉丁裔面临着不同的冠心病风险负担，尤其是当 人口年龄。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/拉丁裔男性中最常见的冠心病危险因素，也是第二大危险因素 女性中常见。此外，人们对高胆固醇的认识、治疗和控制水平 人口非常少。减轻冠心病负担的一种方法是针对性治疗和一级预防 高危人群。遗传风险评分 (GRS) 已在欧洲血统人群中用于识别那些 发生冠心病事件的风险较高，并且谁将从他汀类药物治疗中受益最多。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 的学习。虽然许多表型-基因型关联已在人群中推广，但 由于连锁差异，源自欧洲血统群体的 GRS 可能不是最佳的 不平衡、等位基因频率和遗传结构；尽管如此，研究表明，选择遗传 来自欧洲血统人群的强大全基因组关联研究（GWAS）文献中的变异 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 在未受研究的人群中。本研究的目的是利用先前构建的 GRS，使用 权重源自多种族队列分析，其中包括一小部分拉丁裔，以评估其 与 HCHS/SOL 队列中的事件 CHD 关联，以评估 GRS 与事件的关联 他汀类药物使用者的冠心病，并评估 GRS 是否比传统风险更好地预测冠心病 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 对缩小居住在美国的西班牙裔/拉丁裔的健康差距具有影响，并倡导 遗传研究中的不同人群。本提案中纳入的活动（研究设计、高级 统计、定量/计算方法和研究结果的呈现）涵盖了一组基本的 进入遗传流行病学跨学科领域的科学家所需要的研究技能 精准公共卫生。从开展这项研究中获得的应用经验与教学相结合 培训和个人指导，包括作为平台的综合研究培训计划 开启我作为遗传流行病学独立研究者的职业生涯。