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（GWAS）的益处限制了向更少的人的转移性。 研究少数民族。GWAS的参与者通常具有欧洲血统， 从GWAS中获得的基因组见解取决于两个历史时期人群的密切关系 或特征。因此，在对疾病的理解方面， 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 少数群体，包括有限的队列规模，缺乏基因组资源，和混合历史， 可能使研究设计和分析复杂化的人群结构。然而，对少数群体的重点研究 人口，即使样本量较小，已被证明可以提供特定人群的遗传见解。 该提案的目标是（1）为夏威夷土著少数民族人口提供基因组资源 准确和系统的分析所必需的，（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 这些目标将有助于减少夏威夷土著人当前和未来研究的障碍，并缩小以下方面的差距 我们对他们人群健康的理解。为了实现这一目标，目标1和目标2专注于创建 一个插补参考面板和重组地图具体到夏威夷土著人，分别。一个 特定于群体插补参考组已被证明提高了 常见和罕见的变异，否则将不包括在遗传研究中。重组图谱 是在基于单倍型的推断（例如本地祖先推断或身份推断）中利用的关键资源， 通过血统段检测），这对于混合人口如夏威夷土著人至关重要。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， 与复杂性状相关的基因组区域。我们将利用预期的有害等位基因的增加 在纯合状态下发现，并使用血统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升高（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土著人和相关的基因组资源。 人口，但也探索性状和疾病之间的关系，可能会影响所有人群。

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.