Genetic and multi-omic insights into inflammation and metabolism in a French Polynesian cohort
Year: 2026
Type: article
Abstract: Inflammatory and metabolic diseases are a major global health burden, and their genetic mechanisms differ between populations. 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. Here we combine whole-genome sequencing with blood metabolite and gene-activity profiling in a gout-focused cohort of 1,043 French Polynesian participants, and show that such variants shape molecular traits and disease risk. Hundreds alter metabolite levels, gene expression or splicing but are absent or rare in global reference datasets. Findings include a gene-disrupting variant in ANGPTL8 that lowers lipids and inflammatory markers; an LRMDA variant linked to type 2 diabetes; and a signal at the alpha-globin locus suggestive of thalassemia trait. Integrating molecular and phenotypic data further implicates WDR1 as an additional causal gout gene at the SLC2A9 locus. Genomic research in underrepresented populations thus reveals broadly relevant disease mechanisms. A study of French Polynesians found hundreds of genetic variants that are common locally but rare worldwide and that alter metabolite levels and gene activity, including variants linked to lipid levels, type 2 diabetes and gout.
Source: Nature Communications
Authors: Tristan Pascart, Iman Hamid, Anne-Katrin Emde, Olivia A. Gray, Jaye Moors, Baptiste Gérard, Melissa Hendershott, Sarah LeBaron von Baeyer, Vehia Wheeler, Mathilde Boissel, Erwan Oehler, Valérie Chune, Thomas Bardin, Cristian Preda, Megan Leask, Laura Yerges-Armstrong, Kaja A. Wasik, Keolu Fox, Tony R. Merriman, Stephane E. Castel
Institutions: Centre Hospitalier Universitaire de Rouen, Australian National University, University of French Polynesia, Institut Pasteur de Lille, Université Paris Cité, Bioscar, Hôpital Lariboisière, Université de Lille, Centre Hospitalier Universitaire de Lille, Centrale Lille Institut, University of Otago, University of California San Diego, University of Alabama at Birmingham
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7223471890
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