{"doi":"10.1371/journal.pmed.1003972","title":"Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts","abstract":"BACKGROUND: Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. METHODS AND FINDINGS: We analyzed data from 35,759 men and women in the United States participating in the Nurses' Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. CONCLUSIONS: These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.","journal":"PLoS Medicine","year":2022,"id":241486,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6537,"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":230952,"name":"Marta Guasch‐Ferré","orcid":"0000-0001-8525-1404","position":1,"is_corresponding":false},{"id":230951,"name":"Jun Li","orcid":"0000-0003-3519-8638","position":2,"is_corresponding":false},{"id":230953,"name":"Wonil Chung","orcid":"0000-0002-5766-6247","position":3,"is_corresponding":false},{"id":246328,"name":"Yang Hu","orcid":"0000-0002-0200-5951","position":4,"is_corresponding":false},{"id":242825,"name":"Baoshan Ma","orcid":"0000-0003-1629-1968","position":5,"is_corresponding":false},{"id":38870,"name":"Yanping Li","orcid":"0000-0002-0412-2748","position":6,"is_corresponding":false},{"id":6854,"name":"Jae H. Kang","orcid":"0000-0003-4812-0557","position":7,"is_corresponding":false},{"id":264806,"name":"Peter Kraft","orcid":"0000-0002-4472-8103","position":8,"is_corresponding":false},{"id":35194,"name":"Liming Liang","orcid":"0000-0001-8261-3174","position":9,"is_corresponding":false},{"id":246331,"name":"Qi Sun","orcid":"0000-0002-8480-1563","position":10,"is_corresponding":false},{"id":21957,"name":"Paul W. Franks","orcid":"0000-0002-0520-7604","position":11,"is_corresponding":false},{"id":11268,"name":"JoAnn E. Manson","orcid":"0000-0002-9426-7595","position":12,"is_corresponding":false},{"id":806219,"name":"Walter C. Willet","orcid":null,"position":13,"is_corresponding":false},{"id":1150,"name":"José C. Florez","orcid":"0000-0002-1730-9325","position":14,"is_corresponding":false},{"id":55333,"name":"Frank B. Hu","orcid":"0000-0002-8233-6274","position":15,"is_corresponding":false},{"id":521105,"name":"Jordi Merino","orcid":"0000-0001-8312-1438","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:22:56.227656Z","pmid":"35472203","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":[]}