Comparative genetic architectures of schizophrenia in East Asian and European populations

• Published in: Nature genetics Vol. 51; no. 12; pp. 1670 - 1678
• Main Authors: Lam, Max, Chen, Chia-Yen, Li, Zhiqiang, Martin, Alicia R., Bryois, Julien, Ma, Xixian, Gaspar, Helena, Ikeda, Masashi, Benyamin, Beben, Brown, Brielin C., Liu, Ruize, Zhou, Wei, Guan, Lili, Kamatani, Yoichiro, Kim, Sung-Wan, Kubo, Michiaki, Kusumawardhani, Agung A. A. A., Liu, Chih-Min, Ma, Hong, Periyasamy, Sathish, Takahashi, Atsushi, Xu, Zhida, Yu, Hao, Zhu, Feng, Chen, Wei J., Faraone, Stephen, Glatt, Stephen J., He, Lin, Hyman, Steven E., Hwu, Hai-Gwo, McCarroll, Steven A., Neale, Benjamin M., Sklar, Pamela, Wildenauer, Dieter B., Yu, Xin, Zhang, Dai, Mowry, Bryan J., Lee, Jimmy, Holmans, Peter, Xu, Shuhua, Sullivan, Patrick F., Ripke, Stephan, O’Donovan, Michael C., Daly, Mark J., Qin, Shengying, Sham, Pak, Iwata, Nakao, Hong, Kyung S., Schwab, Sibylle G., Yue, Weihua, Tsuang, Ming, Liu, Jianjun, Ma, Xiancang, Kahn, René S., Shi, Yongyong, Huang, Hailiang
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2019; Nature Publishing Group
• Subjects: 45/43; 45/47; 631/208/205/2138; 692/699/476/1799; Agriculture; Animal Genetics and Genomics; Asian Continental Ancestry Group - genetics; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Bipolar disorder; Cancer Research; Case-Control Studies; Comparative analysis; Consortia; European Continental Ancestry Group - genetics; Far East; Gene Function; Gene loci; Gene mapping; Genealogy; Genetic aspects; Genetic diversity; Genetic research; Genetic variance; Genetics, Population; Genome-Wide Association Study; Genomes; Genomics; Human Genetics; Humans; Mapping; Medical colleges; Medicin och hälsovetenskap; Mental disorders; Meta-analysis; Neurophysiology; Polymorphism, Single Nucleotide; Populations; Principal components analysis; Psychiatry; Quality control; Risk; Schizophrenia; Schizophrenia - genetics; Studies; Type 2 diabetes; Working groups; Far East; Singapore; Australia; Japan; China; Taiwan
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/s41588-019-0512-x

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. Genome-wide meta-analysis with individuals of East Asian or European ancestry identifies 176 loci associated with schizophrenia. Despite consistent genetic effects across populations, polygenic risk models trained in one population have reduced performance in the other population.