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.