Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity.

ABSTRACT: 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/m² in the European subpopulation and 24.2 (22.9-25.5) kg/m² in the East Asian subpopulation; after adjusting for cluster-specific genetic risk

SUBMITTER: Smith K 

PROVIDER: S-EPMC10557820 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature