Contribution of copy number variants to schizophrenia in East Asian populations

Abstract Studies on schizophrenia-associated rare copy number variants (CNVs) have predominantly focused on people of European (EUR) ancestry. Here we present a rare CNV study of schizophrenia in East Asian (EAS) populations, comprising 20,903 cases and 23,258 controls. We observed a significantly elevated genome-wide rare CNV burden in EAS cases compared with controls. Cross-population comparisons showed largely consistent rare CNV effects on schizophrenia risk. In the EAS sample, we identified nine genome-wide-significant schizophrenia-associated rare CNV loci. Meta-analysis with EUR data yielded 14 significant loci, including 8 that reached genome-wide significance for the first time. Genes within these 14 loci were significantly less tolerant to loss-of-function variants than genes in other CNV loci. The new rare CNVs associated with schizophrenia in EAS populations showed higher carrier frequencies in EAS than in EUR populations (0.38% versus 0.0017%). Overall, this study underscores the importance of increasing population diversity to fully capture the genetic underpinnings of schizophrenia.

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Publication Details

Journal
Nature Genetics
Published
2026-09-11
DOI
https://doi.org/10.1038/s41588-026-02732-6
Primary Topic
Genomic variations and chromosomal abnormalities
Type
article
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0.00

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article

Contribution of copy number variants to schizophrenia in East Asian populations

Ikuo Otsuka, Woojae Myung, Makoto Arai, Qidi Feng et al.
Nature Genetics
Genomic variations and chromosomal abnormalities
article

Contribution of copy number variants to schizophrenia in East Asian populations

Ikuo Otsuka, Woojae Myung, Makoto Arai, Qidi Feng, Daniel P. Howrigan, Yaoyao Sun, Calwing Liao, Max Lam, Masanari Itokawa, Nakao Iwata, Benjamin M. Neale, Chih‐Min Liu, Jack Fu, Taishiro Kishimoto, Young‐Chul Chung, Akitoyo Hishimoto, Hiroshi Kunugi, Justin D. Tubbs, Se-joo Kim, Yujiro Yoshihara, Norio Ozaki, Masayuki Ide, Tetsuaki Arai, Kazufumi Akiyama, Yunfeng Ruan, Yoichiro Takayanagi, Kyooseob Ha, Ichiro Sora, Naohiro Arai, Takahiro A. Kato, Bhooma Thiruvahindrapuram, Hideyuki Okano, Mingrui Yu, Hai‐Gwo Hwu, Stephen W. Scherer, Stephen J. Glatt, Alice Zheng, Omar Shanta, Itaru Kushima, Eun‐Jeong Joo, Kotaro Hattori, Yanhui Liao, Shogyoku Bun, Bimal Jana, Takeo Yoshikawa, Zhenglin Guo, Akira Sawa, Hiroki Ishiguro, Kumiko Fujii, Kang Sim, Jen-Pang Wang, Juan Xu, Sayuri Ishiwata, Tetsuro Ohmori, Robert Ye, Heon‐Jeong Lee, Kyung-Sue Hong, Michihiro Toritsuka, Yasue Horiuchi, Dieter B. Wildenauer, Shigenobu Kanba, Shanshan Chen, Sung‐Wan Kim, Feng Zhu, Jess Wang, Takeo Saito, Teruhiko Higuchi, Cong Huai, Byung‐Dae Lee, Kazutaka Shimoda, Shusuke Numata, Jimmy Lee, Mark J. Daly, Guorui Zhao, René Kahn, Yong-Min Ahn, Wenzhao Shi, Ming Tsuang, Agung Kusumawardhani, Jun Miyata, Jianjun Liu, Michio Suzuki, Se-Hyun Kim, Shuken Boku, Yu Chen, Soyeon Kim, Masashi Ikeda, Masaru Mimura, Stanley Global Asia Initiatives, Hideto Niimura, Hong-Hee Won, Minoru Takebayashi, Toshiya Murai, Ruize Liu, Yuji Ozeki, Ji-Hyun Baek, Makoto Kinoshita, Sibylle G. Schwab, Lu Shen, Tomoko Toyota
article en

Abstract

Abstract Studies on schizophrenia-associated rare copy number variants (CNVs) have predominantly focused on people of European (EUR) ancestry. Here we present a rare CNV study of schizophrenia in East Asian (EAS) populations, comprising 20,903 cases and 23,258 controls. We observed a significantly elevated genome-wide rare CNV burden in EAS cases compared with controls. Cross-population comparisons showed largely consistent rare CNV effects on schizophrenia risk. In the EAS sample, we identified nine genome-wide-significant schizophrenia-associated rare CNV loci. Meta-analysis with EUR data yielded 14 significant loci, including 8 that reached genome-wide significance for the first time. Genes within these 14 loci were significantly less tolerant to loss-of-function variants than genes in other CNV loci. The new rare CNVs associated with schizophrenia in EAS populations showed higher carrier frequencies in EAS than in EUR populations (0.38% versus 0.0017%). Overall, this study underscores the importance of increasing population diversity to fully capture the genetic underpinnings of schizophrenia.

Nature Genetics
Broad Institute (US), Chonnam National University (KR), Agency for Science, Technology and Research (SG), University of Helsinki (FI), Kyushu University (JP), Harvard University (US), Seoul National University (KR), Central South University (CN), University of British Columbia (CA), Johns Hopkins University (US), Fujita Health University (JP), University of Tsukuba (JP), Shiga University of Medical Science (JP), National Health Research Institutes (TW), National University of Singapore (SG), National Taiwan University (TW), Nanyang Technological University (SG), The University of Western Australia (AU), Shanghai Jiao Tong University (CN), University of Toronto (CA), Yonsei University (KR), Korea University (KR), Peking University (CN), SUNY Upstate Medical University (US), Keio University (JP), University of Wollongong (AU), Eulji University (KR), Kyoto University (JP), RIKEN Center for Brain Science (JP), Hospital for Sick Children (CA), Samsung Medical Center (KR), Sir Run Run Shaw Hospital (CN), Seoul National University Bundang Hospital (KR), University of Indonesia (ID), Kyung Hee University (KR), University of California San Diego (US), Massachusetts General Hospital (US), Illawarra Health and Medical Research Institute (AU), Digital China Health (China) (CN), Tokyo Metropolitan Institute of Medical Science (JP), National Center of Neurology and Psychiatry (JP), Pusan National University Hospital (KR), First Affiliated Hospital of Xi'an Jiaotong University (CN), National Taiwan University Hospital (TW), Institute for Molecular Medicine Finland (FI), Institute of Mental Health (SG), SickKids Foundation (CA), RIKEN Center for Integrative Medical Sciences (JP), Second Xiangya Hospital of Central South University (CN), Peking University Sixth Hospital (CN), Hangzhou Medical College (CN), University of Toyama (JP), Nagoya University (JP), Nara Medical University (JP), Kobe University (JP), Genome Institute of Singapore (SG), University of Yamanashi (JP), Zhejiang University (CN), Dokkyo Medical University (JP), Jeonbuk National University (KR), Sungkyunkwan University (KR), Tokushima University (JP), Kumamoto University (JP), Icahn School of Medicine at Mount Sinai (US)
Stanley Center for Psychiatric Research, Broad Institute
Openalex Percentile: Top 11%
Genomic variations and chromosomal abnormalities
DOIOpen Access PDFOpenAlex
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