Polynesian genomes reveal rare variants shaping gout, diabetes and blood lipids

A whole-genome sequencing study of 1,043 French Polynesian participants has uncovered hundreds of genetic variants that are common in Polynesian communities but absent or rare in global reference datasets, and that influence metabolite levels, gene expression and gene splicing. The cohort was assembled with a focus on gout, an inflammatory disease whose genetic mechanisms are known to differ between populations. The findings, published in Nature Communications, combine genome sequences with blood metabolite measurements and gene-activity profiling.

Among the specific discoveries, the researchers identified a gene-disrupting variant in ANGPTL8 that is associated with lower lipid levels and lower inflammatory markers. They also found a variant in LRMDA linked to type 2 diabetes, and a signal at the alpha-globin locus suggestive of thalassemia trait, an inherited blood condition affecting hemoglobin production.

By integrating the molecular data with phenotypic information, the study further implicated WDR1 as an additional causal gene for gout at the SLC2A9 locus, a genomic region previously associated with the disease. This connects a locally common variant to a molecular mechanism relevant to gout risk.

The stepwise settlement of the Pacific has left Polynesian communities with variants that are locally common and globally rare, yet these communities remain underrepresented in genomic research. Because most global reference datasets lack these variants, their effects on molecular traits and disease risk have largely gone undetected. The study shows that sequencing underrepresented populations can reveal disease mechanisms with relevance beyond the population studied.

The work is an observational genetic association study in a single cohort; the reported links between variants and traits are associations, and the alpha-globin finding is described as suggestive rather than definitive. The article was released as an accepted, peer-reviewed version ahead of final editorial formatting and remains subject to further edits before the final version of record.

Subject of Research: Genetic and multi-omic analysis of inflammation- and metabolism-related traits in an underrepresented French Polynesian cohort

Article Title: Genetic and multi-omic insights into inflammation and metabolism in a French Polynesian cohort

Article References: Pascart, T., Hamid, I., Emde, A.-K., Gray, O. A., Moors, J., Gérard, B., Hendershott, M., LeBaron von Baeyer, S., Wheeler, V., Boissel, M., Oehler, E., Chune, V., Bardin, T., Preda, C., Leask, M., Yerges-Armstrong, L., Wasik, K. A., Fox, K., Merriman, T. R., & Castel, S. E. (2026). Genetic and multi-omic insights into inflammation and metabolism in a French Polynesian cohort. Nature Communications. https://doi.org/10.1038/s41467-026-78816-y

Image Credits: AI Generated

DOI: 10.1038/s41467-026-78816-y

Keywords: genomics, French Polynesia, gout, type 2 diabetes, whole-genome sequencing, blood metabolites, ANGPTL8, SLC2A9, underrepresented populations, gene expression, thalassemia trait, multi-omics