Nature genetics · 2026
Contribution of copy number variants to schizophrenia in East Asian populations.
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Chen Yu, Feng Qidi, Lam Max, Yu Mingrui, Sun Yaoyao, Huai Cong, Jana Bimal, Fu Jack, Liao Calwing, Ye Robert, Kim Soyeon, Tubbs Justin D, Shanta Omar, Thiruvahindrapuram Bhooma, Jen Yawen, Zhao Guorui, Wang Jess, Stanley Global Asia Initiatives, Xu Juan, Shi Wenzhao, Scherer Stephen W, Zhu Feng, Liu Chih-Min, Guo Zhenglin, Howrigan Daniel, Daly Mark, Neale Benjamin M, Sawa Akira, Sebat Jonathan, Talkowski Michael E, Tang Jinsong, Ma Xiancang, Chen Wei J, Qin Shengying, Yue Weihua, Ge Tian, Huang Hailiang
Аннотация
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.