{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T20:41:06Z","timestamp":1777063266120,"version":"3.51.4"},"reference-count":22,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["19\/0005994"],"award-info":[{"award-number":["19\/0005994"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["19\/005971"],"award-info":[{"award-number":["19\/005971"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["21\/0006335"],"award-info":[{"award-number":["21\/0006335"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007885","name":"European Association for the Study of Diabetes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007885","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T00200X\/1"],"award-info":[{"award-number":["MR\/T00200X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Exeter Biomedical Research Centre"},{"DOI":"10.13039\/501100019434","name":"NIHR Exeter Clinical Research Facility","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013589","name":"Research England","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013589","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["219606\/Z\/19\/Z"],"award-info":[{"award-number":["219606\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223187\/Z\/21\/Z"],"award-info":[{"award-number":["223187\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224600\/Z\/21\/Z"],"award-info":[{"award-number":["224600\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>ONECUT1 (also known as HNF6) is a transcription factor involved in pancreatic development and \u03b2-cell function. Recently, biallelic variants in ONECUT1 were reported as a cause of neonatal diabetes mellitus (NDM) in two subjects, and missense monoallelic variants were associated with type 2 diabetes and possibly maturity-onset diabetes of the young (MODY). Here we examine the role of ONECUT1 variants in NDM, MODY, and type 2 diabetes in large international cohorts of subjects with monogenic diabetes and &amp;gt;400,000 subjects from UK Biobank. We identified a biallelic frameshift ONECUT1 variant as the cause of NDM in one individual. However, we found no enrichment of missense or null ONECUT1 variants among 484 individuals clinically suspected of MODY, in whom all known genes had been excluded. Finally, using a rare variant burden test in the UK Biobank European cohort, we identified a significant association between heterozygous ONECUT1 null variants and type 2 diabetes (P = 0.006) but did not find an association between missense variants and type 2 diabetes. Our results confirm biallelic ONECUT1 variants as a cause of NDM and highlight monoallelic null variants as a risk factor for type 2 diabetes. These findings confirm the critical role of ONECUT1 in human \u03b2-cell function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db23-0498","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T15:34:45Z","timestamp":1693236885000},"page":"1729-1734","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":17,"title":["The Role of\n                    <i>ONECUT1<\/i>\n                    Variants in Monogenic and Type 2 Diabetes Mellitus"],"prefix":"10.2337","volume":"72","author":[{"given":"James","family":"Russ-Silsby","sequence":"first","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-8104","authenticated-orcid":false,"given":"Kashyap A.","family":"Patel","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-0089","authenticated-orcid":false,"given":"Thomas W.","family":"Laver","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3367-789X","authenticated-orcid":false,"given":"Gareth","family":"Hawkes","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-6687","authenticated-orcid":false,"given":"Matthew B.","family":"Johnson","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew N.","family":"Wakeling","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prashant P.","family":"Patil","sequence":"additional","affiliation":[{"name":"2The Society for the Rehabilitation of Crippled Children Narayana Health Children's Hospital, Mumbai, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-473X","authenticated-orcid":false,"given":"Andrew T.","family":"Hattersley","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-6135","authenticated-orcid":false,"given":"Michael N.","family":"Weedon","sequence":"additional","affiliation":[{"name":"1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, 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