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Comparative genetic architectures of schizophrenia in East Asian and European populations

Lam, Max, Chen, Chia-Yen, Li, Zhiqiang, Martin, Alicia, Bryois, Julien, Ma, Xixian, Gaspar, Helena, Ikeda, Masashi, Beben, Benyamin, Brown, Brielin, Liu, Ruize, Wei, Zhou, Guan, Lili, Kamatani, Yoichiro, Kim, Sung-Wan, Kubo, Michiaki, Kusumawardhani, Agung, Liu, Chih-Min, Ma, Hong, Periyasamy, Sathish, Takahash, Atsushi, Xu, Zhida, Yu, Hao, Zhu, Feng, Chen, Wei, Faraone, Stephen, Glatt, Stephen, He, Lin, Hyman, Steven, Hwu, Hai-Gwo, McCarrol, Hwu, Neale, Benjamin, Sklar, Pamela, Wildenauer, Dieter, Yu, Xin, Zhan, Dai, Mowry, Bryan, Lee, Jimmy, Holmans, Peter, Xu, Shuhua, Sullivan, Patrick, Ripke, Stephan, O'Donovan, Michael, Daly, Mark, Qin, Shengying, Sham, Pak, Iwata, Nakao, Hong, Kyung, Schwab, Sibylle, Yue, Weihua, Tsuang, Ming, Liu, Jianjun, Ma, Xiancang, Kahn, René, Shi, Yongyong and Huang, Hailiang 2019. Comparative genetic architectures of schizophrenia in East Asian and European populations. Nature Genetics 51 , pp. 1670-1678. 10.1038/s41588-019-0512-x

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Abstract

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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Publisher: Nature
ISSN: 1061-4036
Date of First Compliant Deposit: 28 August 2019
Date of Acceptance: 5 June 2019
Last Modified: 22 May 2020 14:23
URI: http://orca.cf.ac.uk/id/eprint/125116

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