{"doi":"10.1172/jci197100","title":"Clonal hematopoiesis driven by Dnmt3a mutations promotes metabolic disease development in mice","abstract":"Clonal hematopoiesis (CH) is associated with an increased risk of non-hematologic chronic diseases including metabolic disorders, yet the causality remains poorly defined.DNMT3A is the most altered gene in CH, commonly through monoallelic loss-of-function (LOF) and Arg882His (RH) mutations.Here we demonstrate in a mouse model that CH driven by Dnmt3a RH and especially LOF promotes obesity, diabetes, and chronic liver disease, further exacerbated by high-fat diet (HFD). MainClonal hematopoiesis (CH) is defined as expansion of a blood-cell clone marked with somatic mutations absent diagnosis of hematologic malignancies.In addition to a risk of future leukemia, CH is notably associated with chronic nonhematologic diseases, such as inflammatory disorders and cardiovascular disease(1).Epidemiological studies found CH, especially driven by TET2 loss, was enriched in individuals with overweight, type 2 diabetes (T2D), and chronic liver disease(2, 3).Whether CH is a cause or a consequence of these comorbidities-a question of high translational significance-is incompletely understood.","journal":"Journal of Clinical Investigation","year":2025,"id":520154,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1046137,"name":"Qingchen Yuan","orcid":"0000-0003-4999-3931","position":1,"is_corresponding":false},{"id":1327928,"name":"Marco M. Buttigieg","orcid":"0000-0002-9584-9861","position":2,"is_corresponding":false},{"id":720235,"name":"Prabhjot Kaur","orcid":null,"position":3,"is_corresponding":false},{"id":1062037,"name":"Annalisse Mckee","orcid":null,"position":4,"is_corresponding":false},{"id":719726,"name":"Daniil E. Shabashvili","orcid":"0000-0003-4066-7953","position":5,"is_corresponding":false},{"id":860769,"name":"Caitlyn Vlasschaert","orcid":"0009-0003-8466-7602","position":6,"is_corresponding":false},{"id":27378,"name":"Alexander G. Bick","orcid":"0000-0001-5824-9595","position":7,"is_corresponding":false},{"id":270323,"name":"Michael J. Rauh","orcid":"0000-0002-8346-5537","position":8,"is_corresponding":false},{"id":589288,"name":"Olga A. Guryanova","orcid":"0000-0002-6514-8466","position":9,"is_corresponding":false},{"id":337659,"name":"Bowen Yan","orcid":"0000-0003-4730-6763","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T02:49:23.618703Z","pmid":"41027007","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":[]}