{"doi":"10.1001/jama.2014.6511","title":"Association of a Low-Frequency Variant in<i>HNF1A</i>With Type 2 Diabetes in a Latino Population","abstract":null,"journal":"JAMA","year":2014,"id":602531,"datarank":0.8419692159582107,"base_score":5.6131281063880705,"endowment":5.6131281063880705,"self_citation_contribution":0.8419692159582107,"citation_network_contribution":0.0,"self_endowment_contribution":0.8419692159582107,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":273,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336163,"name":"Ingvild Aukrust","orcid":"0000-0002-4379-5654","position":1,"is_corresponding":false},{"id":338085,"name":"Lise Bjørkhaug","orcid":null,"position":2,"is_corresponding":false},{"id":16104,"name":"Noël P. Burtt","orcid":null,"position":3,"is_corresponding":false},{"id":79259,"name":"Josep M. Mercader","orcid":null,"position":4,"is_corresponding":false},{"id":1545283,"name":"Humberto García-Ortiz","orcid":null,"position":5,"is_corresponding":false},{"id":1077188,"name":"Alicia Huerta-Chagoya","orcid":null,"position":6,"is_corresponding":false},{"id":614890,"name":"Hortensia Moreno-Macías","orcid":"0000-0003-1677-9189","position":7,"is_corresponding":false},{"id":442031,"name":"Geoffrey Walford","orcid":"0000-0001-6896-9625","position":8,"is_corresponding":false},{"id":557682,"name":"Jason Flannick","orcid":"0000-0002-3618-795X","position":9,"is_corresponding":false},{"id":16098,"name":"Amy L. Williams","orcid":"0000-0003-0737-0533","position":10,"is_corresponding":false},{"id":1545287,"name":"María J. Gómez-Vázquez","orcid":null,"position":11,"is_corresponding":false},{"id":1545288,"name":"Juan C. Fernandez-Lopez","orcid":null,"position":12,"is_corresponding":false},{"id":1545289,"name":"Angélica Martínez-Hernández","orcid":null,"position":13,"is_corresponding":false},{"id":557531,"name":"Federico Centeno-Cruz","orcid":"0000-0002-3512-4519","position":14,"is_corresponding":false},{"id":1545290,"name":"Elvia Mendoza-Caamal","orcid":null,"position":15,"is_corresponding":false},{"id":1545291,"name":"Cristina Revilla-Monsalve","orcid":null,"position":16,"is_corresponding":false},{"id":1545292,"name":"Sergio Islas-Andrade","orcid":null,"position":17,"is_corresponding":false},{"id":557534,"name":"Emilio J. Córdova","orcid":"0000-0002-7556-3137","position":18,"is_corresponding":false},{"id":557541,"name":"Xavier Soberón","orcid":"0000-0002-4498-5628","position":19,"is_corresponding":false},{"id":1545293,"name":"María E. González-Villalpando","orcid":null,"position":20,"is_corresponding":false},{"id":1008690,"name":"E. Henderson","orcid":null,"position":21,"is_corresponding":false},{"id":11264,"name":"Lynne R. Wilkens","orcid":"0000-0001-8408-4536","position":22,"is_corresponding":false},{"id":716,"name":"Loic Le Marchand","orcid":null,"position":23,"is_corresponding":false},{"id":1545297,"name":"Olimpia Arellano-Campos","orcid":null,"position":24,"is_corresponding":false},{"id":1545298,"name":"Maria L. Ordóñez-Sánchez","orcid":null,"position":25,"is_corresponding":false},{"id":1545299,"name":"Maribel Rodríguez-Torres","orcid":null,"position":26,"is_corresponding":false},{"id":613207,"name":"Rosario Rodríguez-Guillén","orcid":null,"position":27,"is_corresponding":false},{"id":1545300,"name":"Laura Riba","orcid":null,"position":28,"is_corresponding":false},{"id":338082,"name":"Laeya A. Najmi","orcid":null,"position":29,"is_corresponding":false},{"id":426941,"name":"Suzanne B.R. Jacobs","orcid":"0000-0002-8103-1700","position":30,"is_corresponding":false},{"id":1545301,"name":"Timothy Fennell","orcid":null,"position":31,"is_corresponding":false},{"id":103601,"name":"Stacey Gabriel","orcid":null,"position":32,"is_corresponding":false},{"id":189,"name":"Pierre Fontanillas","orcid":"0000-0002-8944-4454","position":33,"is_corresponding":false},{"id":253983,"name":"Craig L. Hanis","orcid":"0000-0002-4880-5348","position":34,"is_corresponding":false},{"id":16126,"name":"Donna M. Lehman","orcid":"0000-0001-8547-9927","position":35,"is_corresponding":false},{"id":90078,"name":"Christopher P. Jenkinson","orcid":"0000-0002-1862-4714","position":36,"is_corresponding":false},{"id":90082,"name":"Hanna E. Abboud","orcid":null,"position":37,"is_corresponding":false},{"id":16103,"name":"Graeme I. Bell","orcid":null,"position":38,"is_corresponding":false},{"id":1545302,"name":"Maria L. Cortes","orcid":null,"position":39,"is_corresponding":false},{"id":1035,"name":"Michael Boehnke","orcid":"0000-0002-6442-7754","position":40,"is_corresponding":false},{"id":1518048,"name":"Clicerio González-Villalpando","orcid":null,"position":41,"is_corresponding":false},{"id":1099,"name":"Lorena Orozco","orcid":"0000-0002-5801-9180","position":42,"is_corresponding":false},{"id":11270,"name":"Christopher A. Haiman","orcid":"0000-0002-0097-9971","position":43,"is_corresponding":false},{"id":1545303,"name":"Teresa Tusié-Luna","orcid":null,"position":44,"is_corresponding":false},{"id":5021,"name":"Carlos A. Aguilar-Salinas","orcid":null,"position":45,"is_corresponding":false},{"id":16113,"name":"David Altshuler","orcid":"0000-0002-7250-4107","position":46,"is_corresponding":false},{"id":90171,"name":"Pål R. Njølstad","orcid":"0000-0003-0304-6728","position":47,"is_corresponding":false},{"id":1252347,"name":"Jose C. Florez","orcid":null,"position":48,"is_corresponding":false},{"id":1085,"name":"Daniel G. MacArthur","orcid":"0000-0002-5771-2290","position":49,"is_corresponding":false},{"id":21669,"name":"Karol Estrada","orcid":"0000-0003-3224-2955","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Association of a Low-Frequency Variant in<i>HNF1A</i>With Type 2 Diabetes in a Latino Population","abstract":"IMPORTANCE: Latino populations have one of the highest prevalences of type 2 diabetes worldwide. OBJECTIVES: To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships. DESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14,276 participants and characterized in experimental assays. MAIN OUTCOME AND MEASURES: Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function. RESULTS: A single rare missense variant (c.1522G>A [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48; 95% CI, 2.83-10.61; P = 4.4 × 10(-7)) in hepatocyte nuclear factor 1-α (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P = .19). CONCLUSIONS AND RELEVANCE: Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function. This finding may have implications for screening and therapeutic modification in this population, but additional studies are required.","is_dataset_classified":null,"base_score":5.6131281063880705,"endowment":5.6131281063880705,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24915262","pmcid":"PMC4425850","openalex_id":"https://openalex.org/W2055830789","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA054281","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK053889","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"P01 HL045522","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA080205","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA144034","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA80205","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01DK047482","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R35CA53890","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U01 CA063464","title":null},{"funder_name":"NCI NIH HHS","grant_id":"U01 CA164973","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA063464","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA055069","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK098032","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK062370","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01DK085501","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA054281","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK033665","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK042273","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R35 CA053890","title":null},{"funder_name":"NCI NIH HHS","grant_id":"UM1 CA164973","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK020572","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK057295","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01HL24799","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R37 CA054281","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK057295","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01DK085526","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA164973","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA063464","title":null},{"funder_name":"European Commission","grant_id":"293574","title":"Novel Tools for Early Childhood Predisposition to Obesity"}],"total_grants":29,"fwci":23.4919,"citation_percentile":0.99755092,"influential_citations":0,"citation_trend":[{"year":2014,"count":6},{"year":2015,"count":23},{"year":2016,"count":31},{"year":2017,"count":24},{"year":2018,"count":32},{"year":2019,"count":23},{"year":2020,"count":17},{"year":2021,"count":23},{"year":2022,"count":27},{"year":2023,"count":27},{"year":2024,"count":22},{"year":2025,"count":13},{"year":2026,"count":5}],"oa_status":"bronze","license":"other-oa","oa_locations":[{"url":"https://jamanetwork.com/journals/jama/articlepdf/1878720/joi140076.pdf","host_type":"journal"},{"url":"https://jamanetwork.com/journals/jama/articlepdf/1878720/joi140076.pdf","host_type":"publisher"},{"url":"http://jamanetwork.com/journals/jama/fullarticle/1878720","host_type":"publisher"},{"url":"https://doi.org/10.1001/jama.2014.6511","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24915262","host_type":"repository"},{"url":"http://hdl.handle.net/1956/18878","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4425850","host_type":"repository"},{"url":"https://dx.doi.org/10.1001/jama.2014.6511","host_type":""},{"url":"https://hdl.handle.net/1956/18878","host_type":""},{"url":"http://dx.doi.org/10.1001/jama.2014.6511","host_type":""},{"url":"https://doi.org/https://doi.org/10.1001/jama.2014.6511","host_type":""}],"fields_of_study":["Pancreatic function and diabetes","Genetic Associations and Epidemiology","Genomics and Rare Diseases","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Adult","Aged","Diabetes Mellitus, Type 2","Female","Genotype","Hispanic or Latino","Humans","Male","Mexico","Middle Aged","United States","Sequence Analysis, DNA","Age of Onset","Mutation, Missense","Hepatocyte Nuclear Factor 1-alpha"],"keywords":["Medicine","HNF1A","Type 2 diabetes","Diabetes mellitus","Missense mutation","Odds ratio","Population","Allele frequency","Maturity onset diabetes of the young","Internal medicine","Genetics","Allele","Endocrinology","Gene","Mutation","Biology","Adult","Male","Genotype","Mutation, Missense","610","Hispanic or Latino","Sequence Analysis, DNA","Middle Aged","United States","Diabetes Mellitus, Type 2","Humans","Female","Hepatocyte Nuclear Factor 1-alpha","Age of Onset","Mexico","Aged"],"sdg_mappings":[{"sdg_number":2,"sdg_label":"2. Zero hunger"},{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":10,"sdg_label":"10. No inequality"},{"sdg_number":16,"sdg_label":"16. Peace & justice"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T19:39:17.477911Z","pmid":null,"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":[]}