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Publications

Journal Article Ahead of print

PubMed: 42661060 DOI: 10.1038/s41380-026-03853-4

Higher frequencies of CNV deletions in bipolar disorder among Chinese Population.

Mol Psychiatry

Authors: Yong Wu, Xiangyu Li, Yaoyao Sun, Chuyi Zhang, Ping Sun, Li Hui, Ying Zhao, Xiaoyang Feng, Baokun Wang, Jianzhong Yang, Nan Zhang, Jing Yuan, Hongyan Jiang, Yuqi Cheng, Simeng Ma, Qian Gong, Xuyuan Yin, Yongfeng Yang, Wenqiang Li, Luxian Lv, Dongsheng Zhou, Xingxing Li, Xiaogang Chen, Chen Zhang, Xueqin Song, Wenxin Tang, Zhongchun Liu, Yongyong Shi, Xiao Xiao, Weihua Yue, Zhiqiang Li, Ming Li

Affiliations

  • State Key Laboratory of Genetic Evolution & Animal Models, Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
  • The Affiliated Hospital of Qingdao University & The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, Shandong, China.
  • School of Pharmacy, Qingdao University, Qingdao, Shandong, China.
  • Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
  • Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
  • Qingdao Mental Health Center, Qingdao, Shandong, China.
  • Suzhou Guangji Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Physical Education Department, Shanghai Jiao Tong University, Shanghai, China.
  • Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • The Key Laboratory of Mental Disorder Management in Zhejiang Province, Hangzhou, Zhejiang, China.
  • Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
  • Department of Psychiatry, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • The Second Affiliated Hospital of Henan Medical University, Henan Key Lab of Biological Psychiatry, Henan Medical University, Xinxiang, Henan, China.
  • Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China.
  • Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • National Clinical Research Center for Mental Disorders, Changsha, Hunan, China.
  • Clinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei, China.
  • Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China.
  • International Center for Primate Brain Research, Institute of Neuroscience, Center of Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences, Shanghai, China.
  • State Key Laboratory of Genetic Evolution & Animal Models, Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
  • Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
  • Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
  • PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
  • Chinese Institute for Brain Research, Beijing, China.
  • The Affiliated Hospital of Qingdao University & The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, Shandong, China.
  • School of Pharmacy, Qingdao University, Qingdao, Shandong, China.
  • Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China.
  • School of Public Health, Qingdao University, Qingdao, China.
  • State Key Laboratory of Genetic Evolution & Animal Models, Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
  • Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
  • KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Abstract

Although copy number variants (CNVs) represent well-established genetic contributors to schizophrenia (SCZ), their role in bipolar disorder (BD), especially within non-European ancestries, has been inadequately explored. We evaluated the genome-wide load of rare CNVs, encompassing deletions and duplications, in a Han Chinese sample of 3915 BD cases and 7820 ethnically matched controls. We observed a marked overrepresentation of rare deletions in BD patients relative to controls, with affected genes showing enrichment in neural signaling and dosage-dependent networks, indicating that haploinsufficiency in neurodevelopmental loci could underlie a central etiological pathway in BD. Among the 12 previously reported CNV loci from European cohorts, only deletions at 3q29 and 15q11.2 exhibited robust associations with BD susceptibility in Han Chinese individuals. Through genome-wide, gene-centric CNV association testing, we uncovered novel BD-linked loci, including deletions spanning GLIS2 and PAM16 at 16p13.3, GRID2IP at 7p22.1, and CFLAR at 2q33.1, alongside a duplication affecting ZNF878 and ZNF844 at 19p13.2. These disrupted genes are chiefly implicated in neuronal maturation, synaptic modulation, and mitochondrial dynamics. This work delivers the most thorough delineation of BD-associated CNVs in Han Chinese to date, underscoring the imperative for ancestry-inclusive research to comprehensively unravel psychiatric genomics and unveiling fresh mechanistic perspectives on BD etiology.

MeSH

Genes, Bipolar Disorder, Mental Disorders, Genome, Work, Neurosciences