Genomic resources and references for genetic investigation of an understudied population

受研究群体遗传研究的基因组资源和参考资料

• 批准号: 10490836
• 负责人: Bryan Ly Dinh
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490836
• 关键词: Admixture; African American population; Alleles; American; Biotechnology; Cardiovascular Diseases; Characteristics; Chromosome Mapping; Communities; Complex; Cost efficiency; Data; Detection; Disease; Disparity; Drops; European; European ancestry; Frequencies; Functional disorder; Future; Gene Frequency; Genetic; Genetic Markers; Genetic Recombination; Genetic Risk; Genetic Variation; Genetic study; Genomic Segment; Genomics; Genotype; Goals; Haplotypes; Hawaii; Hawaiian population; Health; High Prevalence; Immigration; Incidence; Individual; Investigation; Island; Latino; Linkage Disequilibrium; Maps; Methods; Minority Groups; Morphologic artifacts; Native Hawaiian; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Participant; Polynesian; Population; Population Genetics; Population Sizes; Process; Public Health; Recording of previous events; Research; Research Design; Research Infrastructure; Resource Development; Resources; Risk; Risk Assessment; Sample Size; Scientist; Structure; Technology; Testing; Underserved Population; Variant; Work; cohort; design; disorder risk; experience; genetic analysis; genetic association; genetic resource; genetic risk factor; genome resource; genome wide association study; human disease; identity by descent; improved; insight; rare variant; research and development; theories; tool; trait

Project Summary The benefit of genome-wide association studies (GWAS) unfortunately has limited transferability to less studied minority populations. Participants of GWAS are typically of European descent and transferability of genomic insights gained from GWAS is dependent on how closely related the populations are in either history or characteristics. As a result, there exists a growing disparity when it comes to the understanding of disease incidence and genetic risk factors for non-European populations. There are also factors that impede the study of minority populations including limited cohort size, the lack of genomic resources, and admixture history and population structure that may complicate the study design and analysis. However, focused studies of minority populations, even with smaller sample sizes, have been shown to provide population-specific genetic insights. The goals of this proposal are (1) to generate genomic resources for the Native Hawaiian minority population necessary for accurate and systematic analyses, and (2) to leverage these resources and the unique population history of Native Hawaiians to identify genetic risk factors associated with complex traits. These goals will help reduce the barriers to current and future studies of Native Hawaiians and also reduce the gap in our understanding of health in their population. In order to accomplish this, Aim 1 and Aim 2 focus on creating an imputation reference panel and recombination map specific to the Native Hawaiians, respectively. An imputation reference panel specific to a population has been shown to increase genotype imputation quality of both common and rare variants that would not otherwise be included in a genetic study. A recombination map is a critical resource that is utilized in haplotype-based inference (such as local ancestry inference or identity- by-descent segment detection), which is critical for admixed populations such as the Native Hawaiians. Lastly, in Aim 3, we will use these resources and exploit the population history of the Native Hawaiians to identify genomic regions associated with complex traits. We will leverage the expected increase in deleterious alleles found in homozygous state and use identity-by-descent mapping to identify regions associated with diseases previously shown to have elevated risks in Native Hawaiians (obesity, type-2 diabetes, or cardiovascular diseases). In summary, this work will provide genomic resources specific to the Native Hawaiians and related populations, but also explore the relationship between traits and disease that may impact all populations.

项目摘要 不幸的 研究的少数群体。 GWAS的参与者通常是欧洲下降和可转让性 从GWAS获得的基因组见解取决于人群在任一史中的亲密关系 或特征。结果，在理解疾病时存在越来越大的差异 非欧洲人口的发生率和遗传危险因素。还有一些因素阻碍了研究 少数族裔人口包括有限的队列规模，缺乏基因组资源以及混合历史以及 可能使研究设计和分析复杂化的人群结构。但是，针对少数族裔的研究 人群，即使样本量较小，也已被证明提供了特定于人群的遗传见解。 该提案的目标是（1）为夏威夷原住民人口生成基因组资源 准确有系统的分析所必需的，（2）利用这些资源和独特的资源 夏威夷原住民的人口历史，以识别与复杂性状相关的遗传危险因素。这些 目标将有助于减少夏威夷原住民的当前和未来研究的障碍，并减少差距 我们对他们人口健康的理解。为了实现这一目标，目标1和目标2专注于创建 分别针对本地夏威夷人的参考小组和重组图。一个 已证明特定于人群的参考面板可以提高基因型插补质量 遗传研究中不包含的常见变体和稀有变体。重组图 是基于单倍型的推断中使用的关键资源（例如本地祖先推理或身份 - 偏远地区的检测），这对于像夏威夷原住民这样的混合人群至关重要。最后， 在AIM 3中，我们将使用这些资源并利用夏威夷原住民的人口历史来确定 与复杂性状相关的基因组区域。我们将利用有害等位基因的预期增加 在纯合状态下发现并使用逐渐映射的身份来识别与疾病相关的区域 先前显示的夏威夷本地人（肥胖，2型糖尿病或心血管疾病）的风险升高 疾病）。总而言之，这项工作将提供特定于夏威夷人的基因组资源及相关 人群，但还探讨了可能影响所有人群的特征与疾病之间的关系。