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disorder characterized by alterations between manic\/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene\u2010based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>RNF216<\/jats:italic> gene was significantly associated with BD (odds ratio,\u20094.51 [95% confidence interval, 1.66\u201314.89], false discovery rate &lt;\u200910%). The BD\u2010associated CNV that corresponded with <jats:italic>RNF216<\/jats:italic> also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of <jats:italic>GRM5<\/jats:italic> in this gene set showed a nominal significant association between cases and controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We provide evidence that CNVs in <jats:italic>RNF216<\/jats:italic> and postsynaptic membrane\u2013related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13752","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T09:18:52Z","timestamp":1728983932000},"page":"12-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Copy number variations in <scp><i>RNF216<\/i><\/scp> and postsynaptic membrane\u2013associated genes are associated with bipolar disorder: a case\u2010control study in the Japanese population"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-4837","authenticated-orcid":false,"given":"Masahiro","family":"Nakatochi","sequence":"first","affiliation":[{"name":"Public Health Informatics Unit, Department of Integrated Health Science Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5178","authenticated-orcid":false,"given":"Itaru","family":"Kushima","sequence":"additional","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":"Branko","family":"Aleksic","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-5639","authenticated-orcid":false,"given":"Toshiya","family":"Inada","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youta","family":"Torii","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya 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Toyama Graduate School of Medicine and Pharmaceutical Sciences  Toyama Japan"},{"name":"Research Center for Idling Brain Science University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry University of Toyama Graduate School of Medicine and Pharmaceutical Sciences  Toyama Japan"},{"name":"Research Center for Idling Brain Science University of Toyama  Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro A.","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenobu","family":"Kanba","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Graduate School of Medical Sciences Kyushu University  Fukuoka 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