{"doi":"10.2337/dc22-0295","title":"Questionnaire-Based Polyexposure Assessment Outperforms Polygenic Scores for Classification of Type 2 Diabetes in a Multiancestry Cohort","abstract":"OBJECTIVE: Environmental exposures may have greater predictive power for type 2 diabetes than polygenic scores (PGS). Studies examining environmental risk factors, however, have included only individuals with European ancestry, limiting the applicability of results. We conducted an exposome-wide association study in the multiancestry Personalized Environment and Genes Study to assess the effects of environmental factors on type 2 diabetes. RESEARCH DESIGN AND METHODS: Using logistic regression for single-exposure analysis, we identified exposures associated with type 2 diabetes, adjusting for age, BMI, household income, and self-reported sex and race. To compare cumulative genetic and environmental effects, we computed an overall clinical score (OCS) as a weighted sum of BMI and prediabetes, hypertension, and high cholesterol status and a polyexposure score (PXS) as a weighted sum of 13 environmental variables. Using UK Biobank data, we developed a multiancestry PGS and calculated it for participants. RESULTS: We found 76 significant associations with type 2 diabetes, including novel associations of asbestos and coal dust exposure. OCS, PXS, and PGS were significantly associated with type 2 diabetes. PXS had moderate power to determine associations, with larger effect size and greater power and reclassification improvement than PGS. For all scores, the results differed by race. CONCLUSIONS: Our findings in a multiancestry cohort elucidate how type 2 diabetes odds can be attributed to clinical, genetic, and environmental factors and emphasize the need for exposome data in disease-risk association studies. Race-based differences in predictive scores highlight the need for genetic and exposome-wide studies in diverse populations.","journal":"Diabetes Care","year":2022,"id":266208,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":384208,"name":"Dillon Lloyd","orcid":null,"position":1,"is_corresponding":false},{"id":280462,"name":"Adam Burkholder","orcid":"0000-0002-0237-6920","position":2,"is_corresponding":false},{"id":716990,"name":"Xiaoran Tong","orcid":"0000-0002-4648-3330","position":3,"is_corresponding":false},{"id":386016,"name":"John S. House","orcid":"0000-0002-8447-7871","position":4,"is_corresponding":false},{"id":502490,"name":"Eunice Lee","orcid":"0000-0002-4900-0955","position":5,"is_corresponding":false},{"id":34495,"name":"John B. Buse","orcid":"0000-0002-9723-3876","position":6,"is_corresponding":false},{"id":104613,"name":"Shepherd H. Schurman","orcid":"0000-0002-9133-7906","position":7,"is_corresponding":false},{"id":63126,"name":"David C. Fargo","orcid":"0000-0003-4728-2642","position":8,"is_corresponding":false},{"id":292564,"name":"Charles Schmitt","orcid":"0000-0002-3148-2263","position":9,"is_corresponding":false},{"id":104602,"name":"Janet E. Hall","orcid":"0000-0003-4644-3061","position":10,"is_corresponding":false},{"id":12629,"name":"Alison A. Motsinger‐Reif","orcid":"0000-0003-1346-2493","position":11,"is_corresponding":false},{"id":12245,"name":"Farida S. Akhtari","orcid":"0000-0002-1089-4488","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T00:26:54.081997Z","pmid":"36383734","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":[]}