Multi-omics study of ancestry enriched associations in Hispanics/Latinos

摘要 这项建议建立在我们正在进行的研究遗传学和疾病风险的混合西班牙裔人口。 西班牙裔/拉丁裔是美国较大的种族/少数民族，他们的心脏代谢负担很高， 和炎症相关疾病。从遗传学上讲，西班牙裔是一个异质的人口组成， 多个祖先群体（主要是美洲原住民，西非，欧洲）从最近的混合。几 研究已经利用遗传祖先来解决疾病易感性的差异。本研究将 利用来自大型人口为基础的西班牙裔社区健康研究/研究的综合数据， 拉丁美洲人发现的祖先丰富的易感基因座。我们建议整合基因组学和多- 组学数据，以绘制遗传自祖先群体的基因组片段和变异， 疾病变异频率（目标1），使用新的方法精细定位基因组区域（目标2），以及 验证我们在All of Us研究中发现的西班牙裔/拉丁裔的临床相关性（目标3）。我们期望 深入了解与祖先相关的基因组区域和变异及其与疾病的关系 states.这一提议独特地补充了正在进行的大规模全基因组关联方法。我们的结果 可以提供对混合人群中疾病风险差异的见解。最终，这项研究可以 为个性化医疗提供信息，改善公共卫生。

ABSTRACT This proposal builds into our ongoing research in genetics and disease risk in admixed Hispanic populations. Hispanics/Latinos are the larger racial/ethnic minority in the U.S. They have a high burden of cardiometabolic and inflammatory related diseases. Genetically, Hispanics are an heterogenous population comprised of multiple ancestral groups (primarily Native American, West African, European) from recent admixture. Few studies have leveraged genetic ancestry to address differences in disease susceptibility. This study will leverage the comprehensive data from the large population-based Hispanic Community Health Study/Study of Latinos for discovery of ancestry-enriched susceptibility loci. We propose to integrate genomics and multi- omics data to map genomic segments and variants inherited from the ancestral population with the higher disease variant frequency (Aim 1), use new approaches for fine-mapping genomic regions (Aim 2), and validate our findings for clinical relevance in Hispanics/Latinos from the All of Us study (Aim 3). We expect to gain insights into the identified ancestry-related genomic regions and variants and their relationship to disease states. This proposal uniquely complements large ongoing genome wide association approaches. Our results may provide insights into differences in disease risk in admixed populations. Ultimately this research could inform personalized medicine and improve public health.