Genomic resources and references for genetic investigation of an understudied population

项目摘要 不幸的是，全基因组关联研究的益处将可转移性限制为 研究了少数民族人口。GWAS的参与者通常是欧洲血统和可转让的 从GWAS获得的基因组洞察力取决于两个历史中的种群之间的亲缘关系有多密切 或特征。因此，当涉及到对疾病的理解时，存在着越来越大的差距 非欧洲人群的发病率和遗传风险因素。还有一些因素阻碍了这项研究 包括有限的队列大小，缺乏基因组资源，以及混血史和 可能使研究设计和分析复杂化的人口结构。然而，对少数群体的重点研究 已证明，即使样本量较小的群体也能提供特定于群体的遗传洞察力。 这项提案的目标是(1)为夏威夷土著少数民族人口创造基因组资源 对于准确和系统的分析是必要的，以及(2)利用这些资源和独特的 夏威夷原住民的人口历史，以确定与复杂特征相关的遗传风险因素。这些 目标将有助于减少当前和未来夏威夷原住民研究的障碍，还将缩小 我们对他们人口健康的了解。为了实现这一点，目标1和目标2专注于创造 分别是夏威夷原住民特有的归罪参考图和重组图。一个 已有研究表明，特定于群体的归因参考组可以提高基因的归因质量 既有常见的，也有罕见的变异，否则就不会被纳入基因研究。重组图 是一种关键资源，用于基于单倍型的推理(如本地祖先推理或身份- 按血统片段检测)，这对夏威夷土著等混杂种群至关重要。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长 发现处于纯合子状态，并使用血统定位图来识别与疾病相关的区域 以前显示夏威夷原住民(肥胖症、2型糖尿病或心血管疾病)的风险增加 疾病)。总而言之，这项工作将提供夏威夷原住民和相关物种特有的基因组资源 但也要探索可能影响所有人口的特征和疾病之间的关系。

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.