Comparative genetic architectures of schizophrenia in East Asian and European populations

作者：Lam, Max, Chen, Chia-Yen, Zhiqiang Li, Alicia R. Martin, Julien Bryois, Xixian Ma, Héléna A. Gaspar, Masashi Ikeda, Beben Benyamin, Brielin C. Brown, Ruize Liu, Wei Zhou, Lili Guan, Yoichiro Kamatani, Sung‐Wan Kim, Michiaki Kubo, Agung Kusumawardhani, Chih‐Min Liu, Hong Ma, Sathish Periyasamy, Atsushi Takahashi, Zhida Xu, Hao Yu, Feng Zhu, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Indonesia Schizophrenia Consortium, Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN), Wei J. Chen, Stephen V. Faraone, Stephen J. Glatt, Lin He, Steven E. Hyman, Hai‐Gwo Hwu, Steven A. McCarroll, Benjamin M. Neale, Pamela Sklar, Dieter B. Wildenauer, Xin Yu, Dai Zhang, Bryan Mowry, Jimmy Lee, Peter Holmans, Shuhua Xu, Patrick F. Sullivan, Stephan Ripke, Michael O‘Donovan, Mark J. Daly, Shengying Qin, Pak C. Sham, Nakao Iwata, Kyung Sue Hong, Sibylle G. Schwab, Weihua Yue, Ming T. Tsuang, Jianjun Liu, Xiancang Ma, René S. Kahn, Yongyong Shi, Hailiang Huang · 发表于：Lancaster EPrints (Lancaster University) · 年份：2019 · 被引用次数：84 · 研究领域：Genetic Associations and Epidemiology、Genomic variations and chromosomal abnormalities、Genomics and Rare Diseases

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.