Gout, an arthritic disease that causes joint inflammation from immune responses to urate crystals, was long known as the “disease of kings” and thought to only affect European royalty. Often overlooked, Māori and Pacific people have a prevalence of gout of approximately 6-8%, suggesting genetic factors as a possible contributor. >90% of Genome Wide Association Studies (GWAS), the gold standard for identifying genetic-disease association factors, include only individuals of European ancestry. Marginalized communities continue to be excluded from genetic studies, and resultant medical treatments may be less effective. Consequently, little knowledge exists of the genetic diversity of Polynesian people. Here, we aim to identify high frequency genetic variants specific to Polynesian people in previously identified genes that associate with gout. We used a dataset of 29.2 million genetic variants from a study cohort of 2,593 Polynesian people. The sample was restricted to variants that were: 1) rare (<0.1% minor allele frequency (MAF)) or not reported in 1000 Genomes or the Genome Aggregation Database (gnomAD); 2) common in Polynesia ( >1% MAF), and 3) within candidate gout genes. These variants (n=24,836) were tested in association analyses for gout. We ran logistic regressions and adjusted for age, sex, and principal-component vectors. We identified nine genetic variants within candidate gout genes that were strongly associated (p 1 x 10-4) with gout. These variants may be important for understanding the genetic factors of gout and may ultimately help develop personalized health therapeutics for historically marginalized populations of the Pacific.
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