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Copy number variations in RNF216 and postsynaptic membrane–associated genes are associated with bipolar disorder: a case‐control study in the Japanese population.

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Title: Copy number variations in RNF216 and postsynaptic membrane–associated genes are associated with bipolar disorder: a case‐control study in the Japanese population.
Authors: Nakatochi, Masahiro (AUTHOR), Kushima, Itaru (AUTHOR), Aleksic, Branko (AUTHOR), Kimura, Hiroki (AUTHOR), Kato, Hidekazu (AUTHOR), Inada, Toshiya (AUTHOR), Torii, Youta (AUTHOR), Takahashi, Nagahide (AUTHOR), Yamamoto, Maeri (AUTHOR), Iwamoto, Kunihiro (AUTHOR), Nawa, Yoshihiro (AUTHOR), Iritani, Shuji (AUTHOR), Iwata, Nakao (AUTHOR), Saito, Takeo (AUTHOR), Ninomiya, Kohei (AUTHOR), Okochi, Tomo (AUTHOR), Hashimoto, Ryota (AUTHOR), Yamamori, Hidenaga (AUTHOR), Yasuda, Yuka (AUTHOR), Fujimoto, Michiko (AUTHOR)
Source: Psychiatry & Clinical Neurosciences. Jan2025, Vol. 79 Issue 1, p12-20. 9p.
Subjects: Japanese people, Bipolar disorder, Gene ontology, Odds ratio, Databases
Abstract: Aim: Bipolar disorder (BD) is a common psychiatric 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. Methods: 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‐based 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%. Results: The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66–14.89], false discovery rate < 10%). The BD‐associated CNV that corresponded with RNF216 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 GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05). Conclusion: We provide evidence that CNVs in RNF216 and postsynaptic membrane–related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD. [ABSTRACT FROM AUTHOR]
Copyright of Psychiatry & Clinical Neurosciences is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Copy number variations in RNF216 and postsynaptic membrane–associated genes are associated with bipolar disorder: a case‐control study in the Japanese population.
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Aim: Bipolar disorder (BD) is a common psychiatric 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. Methods: 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‐based 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%. Results: The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66–14.89], false discovery rate &lt; 10%). The BD‐associated CNV that corresponded with RNF216 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 GRM5 in this gene set showed a nominal significant association between cases and controls (P &lt; 0.05). Conclusion: We provide evidence that CNVs in RNF216 and postsynaptic membrane–related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Psychiatry &amp; Clinical Neurosciences is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.1111/pcn.13752
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