{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:02:41Z","timestamp":1791547361731,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21wm0425007"],"award-info":[{"award-number":["JP21wm0425007"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21dm0207075"],"award-info":[{"award-number":["JP21dm0207075"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ak0101113"],"award-info":[{"award-number":["JP21ak0101113"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21dk030710"],"award-info":[{"award-number":["JP21dk030710"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ek0109488"],"award-info":[{"award-number":["JP21ek0109488"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21km0405216"],"award-info":[{"award-number":["JP21km0405216"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ek0109411"],"award-info":[{"award-number":["JP21ek0109411"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06277"],"award-info":[{"award-number":["16H06277"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H05090"],"award-info":[{"award-number":["17H05090"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H04040"],"award-info":[{"award-number":["18H04040"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K07543"],"award-info":[{"award-number":["21K07543"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07942"],"award-info":[{"award-number":["20K07942"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K17087"],"award-info":[{"award-number":["19K17087"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K19720"],"award-info":[{"award-number":["15K19720"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H00194"],"award-info":[{"award-number":["21H00194"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K19511"],"award-info":[{"award-number":["18K19511"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H04815"],"award-info":[{"award-number":["21H04815"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008667","name":"SENSHIN Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Eating disorders (EDs) are complex, multifactorial psychiatric conditions. Previous studies identified pathogenic copy number variations associated with NDDs (NDD\u2010CNVs) in ED patients. However, no statistical evidence for an association between NDD\u2010CNVs and EDs has been demonstrated. Therefore, we examined whether NDD\u2010CNVs confer risk for EDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using array comparative genomic hybridization (aCGH), we conducted a high\u2010resolution CNV analysis of 71 severe female ED patients and 1045 female controls. According to the American College of Medical Genetics guidelines, we identified NDD\u2010CNVs or pathogenic\/likely pathogenic CNVs in NDD\u2010linked loci. Gene set analysis was performed to examine the involvement of synaptic dysfunction in EDs. Clinical data were retrospectively examined for ED patients with NDD\u2010CNVs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the samples analyzed with aCGH, 70 severe ED patients (98.6%) and 1036 controls (99.1%) passed our quality control filtering. We obtained 189 and 2539 rare CNVs from patients and controls, respectively. NDD\u2010CNVs were identified in 10.0% (7\/70) of patients and 2.3% (24\/1036) of controls. Statistical analysis revealed a significant association between NDD\u2010CNVs and EDs (odds ratio\u00a0=\u00a04.69, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0023). NDD\u2010CNVs in ED patients included 45,X and deletions at <jats:italic>KATNAL2<\/jats:italic>, <jats:italic>DIP2A<\/jats:italic>, <jats:italic>PTPRT<\/jats:italic>, <jats:italic>RBFOX1<\/jats:italic>, <jats:italic>CNTN4<\/jats:italic>, <jats:italic>MACROD2<\/jats:italic>, and <jats:italic>FAM92B<\/jats:italic>. Four of these genes were related to synaptic function. In gene set analysis, we observed a nominally significant enrichment of rare exonic CNVs in synaptic signaling in ED patients (odds ratio\u00a0=\u00a02.55, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0254).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study provides the first preliminary evidence that NDD\u2010CNVs may confer risk for severe EDs. The pathophysiology may involve synaptic dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13430","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T10:29:09Z","timestamp":1653474549000},"page":"423-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Contribution of copy number variations to the risk of severe eating disorders"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5178","authenticated-orcid":false,"given":"Itaru","family":"Kushima","sequence":"first","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Medical Genomics Center Nagoya University Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Imaeda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Clinical Oncology and Chemotherapy Nagoya University Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"National Hospital Organization Higashiowari National Hospital  Nagoya Japan"},{"name":"The Clinical Research Center, National Hospital Organization Nagoya Medical Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Oya\u2010Ito","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Nutrition Shubun University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nakatochi","sequence":"additional","affiliation":[{"name":"Public Health Informatics Unit, Department of Integrated Health Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Aleksic","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-4898","authenticated-orcid":false,"given":"Norio","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Institute for Glyco\u2010core Research (iGCORE) Nagoya University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30059-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291720005474"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.114.153221"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.16121402"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0439-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2010.107"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/YPG.0000000000000172"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2112560118"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.022"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0655-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0033-5"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.002"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10989"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjgenmed.2016.27"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13908"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138659"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105778"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3303"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-021-09399-6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.020"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000150542.16969.CC"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.289"},{"key":"e_1_2_8_25_1","article-title":"Depression\u2010like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis","volume":"133","author":"Lim SH","year":"2020","journal-title":"J. Cell Sci."},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100783"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000461"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.181990.114"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2020.1809186"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01223-y"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/eat.20029"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78654-y"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12536"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.88"}],"container-title":["Psychiatry and Clinical Neurosciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcn.13430","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pcn.13430","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcn.13430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T22:47:15Z","timestamp":1692744435000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcn.13430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,20]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1111\/pcn.13430"],"URL":"https:\/\/doi.org\/10.1111\/pcn.13430","archive":["Portico"],"relation":{},"ISSN":["1323-1316","1440-1819"],"issn-type":[{"value":"1323-1316","type":"print"},{"value":"1440-1819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,20]]},"assertion":[{"value":"2022-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}