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Despite this burden, they remain substantially underrepresented in genome-wide association studies (GWAS), limiting discovery of ancestry-relevant disease biology (2). This limits biological insight and hampers genomic discovery. Here we integrated genome-wide signatures of recent positive selection across 13 South Asian populations (3,4) with cross-trait genetic association data (3,4). We identified 1,797 genes residing within regions under recent positive selection and prioritised 65 shared across South Asia. Selection-prioritised loci were enriched for credible sets from the largest trans-ancestry T2D GWAS and for partitioned polygenic score clusters implicated in lipodystrophy-like fat distribution, obesity and proinsulin biology. Multi-trait fine-mapping recovered established T2D loci, including\n                  <jats:italic>RBM6<\/jats:italic>\n                  and\n                  <jats:italic>PEPD<\/jats:italic>\n                  , and identified a signal at\n                  <jats:italic>MAPT<\/jats:italic>\n                  associated with hepatic insulin resistance, erythrocytic traits and HbA1c in two independent south Asian cohorts (5\u20137). These findings demonstrate that signatures of recent positive selection can be integrated with genetic association data to prioritise metabolically relevant loci and provide a complementary route to genetic discovery in underrepresented populations.\n                <\/jats:p>","DOI":"10.64898\/2026.03.12.26348237","type":"posted-content","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:20:23Z","timestamp":1773426023000},"source":"Crossref","is-referenced-by-count":0,"title":["Selection-guided discovery in South Asians implicates the MAPT locus in insulin resistance"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8267-883X","authenticated-orcid":false,"given":"Erwan","family":"Pennarun","sequence":"first","affiliation":[{"name":"Wolfson Institute of Population Health, Queen Mary University of London, United Kingdom"},{"name":"Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, 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