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, 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
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.