{"doi":"10.1101/2023.09.28.23296294","title":"Multi-ancestry Polygenic Mechanisms of Type 2 Diabetes Elucidate Disease Processes and Clinical Heterogeneity","abstract":"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/m 2 in the European subpopulation and 24.2 (22.9- 25.5) kg/m 2 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 2 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.","journal":"medRxiv","year":2023,"id":400978,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9342,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":988242,"name":"Aaron J. Deutsch","orcid":"0000-0001-6750-5335","position":1,"is_corresponding":false},{"id":23916,"name":"Carolyn McGrail","orcid":null,"position":2,"is_corresponding":false},{"id":852452,"name":"Hyunkyung Kim","orcid":"0000-0001-7964-3073","position":3,"is_corresponding":false},{"id":899978,"name":"Sarah Hsu","orcid":"0000-0001-9823-9711","position":4,"is_corresponding":false},{"id":316845,"name":"Ravi Mandla","orcid":"0000-0002-0782-0138","position":5,"is_corresponding":false},{"id":707669,"name":"Philip Schroeder","orcid":"0000-0002-9885-7787","position":6,"is_corresponding":false},{"id":326885,"name":"Kenneth E. Westerman","orcid":"0000-0001-7619-1868","position":7,"is_corresponding":false},{"id":470903,"name":"Łukasz Szczerbiński","orcid":"0000-0002-6201-0605","position":8,"is_corresponding":false},{"id":519738,"name":"Timothy D. Majarian","orcid":"0000-0002-0482-1602","position":9,"is_corresponding":false},{"id":472147,"name":"Varinderpal Kaur","orcid":null,"position":10,"is_corresponding":false},{"id":628967,"name":"Alice Williamson","orcid":"0000-0002-7599-9301","position":11,"is_corresponding":false},{"id":31471,"name":"Melina Claussnitzer","orcid":"0000-0003-2450-736X","position":12,"is_corresponding":false},{"id":1150,"name":"José C. Florez","orcid":"0000-0002-1730-9325","position":13,"is_corresponding":false},{"id":16116,"name":"Alisa K. Manning","orcid":"0000-0003-0247-902X","position":14,"is_corresponding":false},{"id":253982,"name":"Josep M. Mercader","orcid":"0000-0001-8494-3660","position":15,"is_corresponding":false},{"id":16068,"name":"Kyle J. Gaulton","orcid":"0000-0003-1318-7161","position":16,"is_corresponding":false},{"id":7372,"name":"Miriam S. Udler","orcid":"0000-0003-3824-9162","position":17,"is_corresponding":false},{"id":852453,"name":"Kirk Smith","orcid":"0000-0002-4338-4812","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37808749","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}