{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:26:30Z","timestamp":1783398390553,"version":"3.54.6"},"reference-count":37,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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\/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"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,9,3]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>17q12 microdeletion and microduplication syndromes present as overlapping, multisystem disorders. We assessed the disease phenotypes of individuals with 17q12 CNV in a population-based cohort.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated 17q12 CNV using microarray data from 450 993 individuals in the UK Biobank and calculated disease status associations for diabetes, liver and renal function, neurological and psychiatric traits.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 11 17q12 microdeletions and 106 microduplications. Microdeletions were strongly associated with diabetes (p=2\u00d710<jats:sup>\u22127<\/jats:sup>) but microduplications were not. Estimated glomerular filtration rate (eGFR mL\/min\/1.73 m<jats:sup>2<\/jats:sup>) was consistently lower in individuals with microdeletions (p=3\u00d710<jats:sup>\u221212<\/jats:sup>) and microduplications (p=6\u00d710<jats:sup>\u221225<\/jats:sup>). Similarly, eGFR &lt;60, including end-stage renal disease, was associated with microdeletions (p=2\u00d710<jats:sup>\u22129<\/jats:sup>, p&lt;0.003) and microduplications (p=1\u00d710<jats:sup>\u22129<\/jats:sup>, p=0.009), respectively, highlighting sometimes substantially reduced renal function in each. Microduplications were associated with decreased fluid intelligence (p=3\u00d710<jats:sup>\u22124<\/jats:sup>). SNP association analysis in the 17q12 region implicated changes to <jats:italic>HNF1B<\/jats:italic> as causing decreased eGFR (NC_000017.11:g.37741642T&gt;G, rs12601991, p=4\u00d710<jats:sup>\u221221<\/jats:sup>) and diabetes (NC_000017.11:g.37741165C&gt;T, rs7501939, p=6\u00d710<jats:sup>\u221217<\/jats:sup>). A second locus within the region was also associated with fluid intelligence (NC_000017.11:g.36593168T&gt;C, rs1005552, p=6\u00d710<jats:sup>\u22129<\/jats:sup>) and decreased eGFR (NC_000017.11:g.36558947T&gt;C, rs12150665, p=4\u00d710<jats:sup>\u201315<\/jats:sup>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We demonstrate 17q12 microdeletions but not microduplications are associated with diabetes in a population-based cohort, likely caused by <jats:italic>HNF1B<\/jats:italic> haploinsufficiency. We show that both 17q12 microdeletions and microduplications are associated with renal disease, and multiple genes within the region likely contribute to renal and neurocognitive phenotypes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108615","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T13:25:20Z","timestamp":1663248320000},"page":"491-497","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Recurrent 17q12 microduplications contribute to renal disease but not diabetes"],"prefix":"10.1136","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-7615","authenticated-orcid":false,"given":"Stuart","family":"Cannon","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, 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