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.

项目概要 遗憾的是，全基因组关联研究 (GWAS) 的优势限制了其可转移性。 研究了少数民族人口。 GWAS 的参与者通常具有欧洲血统，并且具有可转移性 从 GWAS 获得的基因组见解取决于任一历史中人群的相关程度 或特征。因此，人们对疾病的理解存在越来越大的差异。 非欧洲人群的发病率和遗传风险因素。也有一些因素阻碍了研究 少数族群的数量有限，包括队列规模有限、缺乏基因组资源以及混合历史和 人口结构可能会使研究设计和分析变得复杂。然而，针对少数民族的研究 即使样本量较小，人群也已被证明可以提供特定于人群的遗传见解。 该提案的目标是 (1) 为夏威夷原住民少数民族生成基因组资源 准确和系统分析所必需的，以及（2）利用这些资源和独特的 夏威夷原住民的人口历史，以确定与复杂性状相关的遗传风险因素。这些 目标将有助于减少夏威夷原住民当前和未来研究的障碍，并缩小差距 我们对其人口健康状况的了解。为了实现这一目标，目标 1 和目标 2 重点关注创造 分别针对夏威夷原住民的插补参考面板和重组图。一个 特定人群的插补参考面板已被证明可以提高基因型插补质量 常见和罕见的变异，否则不会包含在基因研究中。重组图谱 是用于基于单倍型的推理（例如本地血统推理或身份推理）的关键资源 按血统分段检测），这对于夏威夷原住民等混合人群至关重要。最后， 在目标 3 中，我们将利用这些资源并利用夏威夷原住民的人口历史来识别 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血统身份映射来识别与疾病相关的区域 先前显示夏威夷原住民的风险较高（肥胖、2 型糖尿病或心血管疾病） 疾病）。总之，这项工作将提供夏威夷原住民和相关人群特有的基因组资源。 人群，还探索可能影响所有人群的性状和疾病之间的关系。