Year: 2026
Type: article
Study design: Observational Study
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.
Source: Nature Genetics
Authors: Yu Chen, Qidi Feng, Max Lam, Mingrui Yu, Yaoyao Sun, Cong Huai, Bimal Jana, Jack Fu, Calwing Liao, Robert Ye, Soyeon Kim, Justin D. Tubbs, Omar Shanta, Bhooma Thiruvahindrapuram, Yawen Jen, Guorui Zhao, Jess Wang, Stanley Global Asia Initiatives, Sibylle G. Schwab, Rene Kahn, Kyung-Sue Hong, Ming Tsuang, Masanari Itokawa, Jianjun Liu, Stephen J. Glatt, Nakao Iwata, Masashi Ikeda, Jimmy Lee, Yunfeng Ruan, Ruize Liu, Yasue Horiuchi, Byung-Dae Lee, Eun-Jeong Joo, Woojae Myung, Kyooseob Ha, Hong-Hee Won, Ji-Hyun Baek, Young-Chul Chung, Sung-Wan Kim, Dieter B. Wildenauer, Agung Kusumawardhani, Hai-Gwo Hwu, Kang Sim, Akitoyo Hishimoto, Ikuo Otsuka, Ichiro Sora, Tomoko Toyota, Takeo Yoshikawa, Hiroshi Kunugi, Kotaro Hattori, Sayuri Ishiwata, Shusuke Numata, Tetsuro Ohmori, Makoto Arai, Yuji Ozeki, Kumiko Fujii, Se-Joo Kim, Heon-Jeong Lee, Yong-Min Ahn, Se-Hyun Kim, Kazufumi Akiyama, Kazutaka Shimoda, Makoto Kinoshita, Teruhiko Higuchi, Alice Zheng, Lu Shen, Takeo Saito, Yanhui Liao, Shanshan Chen, Toshiya Murai, Jun Miyata, Yujiro Yoshihara, Norio Ozaki, Itaru Kushima, Takahiro A. Kato, Shigenobu Kanba, Minoru Takebayashi, Shuken Boku, Toshifumi Kishimoto, Michihiro Toritsuka, Hiroki Ishiguro, Tetsuaki Arai, Masayuki Ide, Michio Suzuki, Yoichiro Takayanagi, Hideyuki Okano, Masaru Mimura, Hideto Niimura, Shogyoku Bun, Naohiro Arai, Juan Xu, Wenzhao Shi, Stephen W. Scherer, Feng Zhu, Chih-Min Liu, Zhenglin Guo, Daniel Howrigan, Mark Daly, Benjamin M. Neale, Akira Sawa, Jonathan Sebat, Michael E. Talkowski, Jinsong Tang, Xiancang Ma, Wei J. Chen, Shengying Qin, Weihua Yue, Tian Ge, Hailiang Huang
Institutions: Broad Institute, Massachusetts General Hospital, Stanley Center for Psychiatric Research, Harvard University, Nanyang Technological University, Institute of Mental Health, Peking University Sixth Hospital, Shanghai Jiao Tong University, Kyung Hee University, University of California San Diego, Hospital for Sick Children, Centre for Applied Genomics, National Health Research Institutes, National Taiwan University, University of Wollongong, Illawarra Health and Medical Research Institute, Icahn School of Medicine at Mount Sinai, University of British Columbia, Tokyo Metropolitan Institute of Medical Science, Agency for Science, Technology and Research, National University of Singapore, Genome Institute of Singapore, SUNY Upstate Medical University, Fujita Health University, Pusan National University Hospital, Eulji University, Seoul National University, Seoul National University Bundang Hospital, Samsung Medical Center, Sungkyunkwan University, Jeonbuk National University, The University of Western Australia, University of Indonesia, Kobe University, RIKEN Center for Integrative Medical Sciences, RIKEN Center for Brain Science, National Center of Neurology and Psychiatry, Tokushima University, Shiga University of Medical Science, Korea University, Dokkyo University, Dokkyo Medical University, Central South University, Sir Run Run Shaw Hospital, Second Xiangya Hospital of Central South University, Xiangya Hospital Central South University, Zhejiang University, Kyoto University, Nagoya University, Kyushu University, Kumamoto University, Nara Medical University, University of Yamanashi, University of Tsukuba, University of Toyama, Keio University, Digital China Health (China), University of Toronto, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, National Taiwan University Hospital, University of Helsinki, Institute for Molecular Medicine Finland, Johns Hopkins University, Peking University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7212308377