Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.

It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining >/=5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment.

Cancer in Kosrae State, Federated States of Micronesia.

Little is known about the impact of cancer and the extent of cancer-related services in Kosrae. The purpose of this study, funded by the National Cancer Institute, was to document the state of cancer awareness and services in Kosrae and to begin to identify cancer-care needs. Findings suggest that cancer is the eighth-leading cause of death in Kosrae, although a number of factors contribute to a possible undercount of cancer cases. Cancer-related services are limited. A number of needs were identified, and an action plan was developed based on three priority areas: 1) establishing a cancer registry; 2) increasing public awareness about cancer risk, prevention, and detection; and 3) expanding cancer screening and detection programs.