{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:55:09Z","timestamp":1768564509598,"version":"3.49.0"},"posted":{"date-parts":[[2023,9,29]]},"group-title":"Genetic and Genomic Medicine","reference-count":41,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  We identified genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from diverse groups, including non-European populations. We implemented soft clustering with 650 T2D-associated genetic variants, capturing known and novel T2D subtypes with distinct cardiometabolic trait associations. The twelve genetic clusters were distinctively enriched for single-cell regulatory regions. Polygenic scores derived from the clusters differed in distribution between ancestry groups, including a significantly higher proportion of lipodystrophy-related polygenic risk in East Asian ancestry. T2D risk was equivalent at a BMI of 30 kg\/m\n                  <jats:sup>2<\/jats:sup>\n                  in the European subpopulation and 24.2 (22.9- 25.5) kg\/m\n                  <jats:sup>2<\/jats:sup>\n                  in the East Asian subpopulation; after adjusting for cluster-specific genetic risk, the equivalent BMI threshold increased to 28.5 (27.1-30.0) kg\/m\n                  <jats:sup>2<\/jats:sup>\n                  in the East Asian group, explaining about 75% of the difference in BMI thresholds. Thus, these multi-ancestry T2D genetic subtypes encompass a broader range of biological mechanisms and help explain ancestry-associated differences in T2D risk profiles.\n                <\/jats:p>","DOI":"10.1101\/2023.09.28.23296294","type":"posted-content","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T14:25:16Z","timestamp":1695997516000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-4812","authenticated-orcid":false,"given":"Kirk","family":"Smith","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6750-5335","authenticated-orcid":false,"given":"Aaron 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H.","family":"Schroeder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-1868","authenticated-orcid":false,"given":"Kenneth E.","family":"Westerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6201-0605","authenticated-orcid":false,"given":"Lukasz","family":"Szczerbinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy 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