@article{e0fa7d3452b9447aa946d488dda811f3,
title = "Comparative genetic architectures of schizophrenia in East Asian and European populations",
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.",
keywords = "Asian Continental Ancestry Group/genetics, Case-Control Studies, European Continental Ancestry Group/genetics, Far East, Genetics, Population, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Schizophrenia/genetics",
author = "Max Lam and Chia-Yen Chen and Zhiqiang Li and Martin, \{Alicia R\} and Julien Bryois and Xixian Ma and Helena Gaspar and Masashi Ikeda and Beben Benyamin and Brown, \{Brielin C\} and Ruize Liu and Wei Zhou and Lili Guan and Yoichiro Kamatani and Sung-Wan Kim and Michiaki Kubo and Kusumawardhani, \{Agung A A A\} and Chih-Min Liu and Hong Ma and Sathish Periyasamy and Atsushi Takahashi and Zhida Xu and Hao Yu and Feng Zhu and Chen, \{Wei J\} and Stephen Faraone and Glatt, \{Stephen J\} and Lin He and Hyman, \{Steven E\} and Hai-Gwo Hwu and McCarroll, \{Steven A\} and Neale, \{Benjamin M\} and Pamela Sklar and Wildenauer, \{Dieter B\} and Xin Yu and Dai Zhang and Mowry, \{Bryan J\} and Jimmy Lee and Peter Holmans and Shuhua Xu and Sullivan, \{Patrick F\} and Stephan Ripke and O'Donovan, \{Michael C\} and Daly, \{Mark J\} and Shengying Qin and Pak Sham and Nakao Iwata and Hong, \{Kyung S\} and Schwab, \{Sibylle G\} and Kahn, \{Ren{\'e} S\}",
note = "Funding Information: We thank K. Kendler, J. McGrath, J. Walters, D. Levinson and M. Owen for helpful discussions. We thank S. Awathi, V. Trubetskoy and G. Panagiotaropoulou for support with the RICOPILI analysis pipeline. We thank SURFsara and Digital China Health for computing infrastructure for this study. M.L. acknowledges the National Medical Research Council Research Training Fellowship award (grant number: MH095:003/008-1014). A.R.M. acknowledges funding from K99MH117229. B.B. acknowledges funding support from the National Health and Medical Research Council (NHMRC; funding numbers 1084417 and 1079583). L.G. acknowledges the National Key Research and Development Program of the Ministry of Science and Technology of China (2016YFC1306802). M.I., Y.K. and N.I. acknowledge the Strategic Research Program for Brain Sciences (grant number JP19dm0107097) and Advanced Genome Research and Bioinformatics Study toFacilitate Medical Innovation (GRIFIN) of Platform Program for Promotion of Genome Medicine (P3GM) (grant numbers JP19km0405201 and JP19km0405208) from the Japan Agency for Medical Research and Development. Y.K., M.K. and A.T. acknowledge the BioBank Japan Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan. S.-W.K. acknowledges a grant of the Korean Mental Health Technology Research and Development Project (HM15C1140). W.J.C. acknowledges the Ministry of Education, Taiwan ({\textquoteleft}Aim for the Top University Project{\textquoteright} to National Taiwan University; 2011–2017), Ministry of Science and Technology, Taiwan (MOST 103-2325-B-002-025), National Health Research Institutes, Taiwan (NHRI-EX104-10432PI), NIH/NHGRI grant U54HG003067, NIMH grant R01 MH085521 and NIMH grant R01 MH085560. S.J.G. acknowledges R01 MH08552. B.J.M. acknowledges Australian NHMRC grant 496698. H.-G.H. acknowledges the Ministry of Education, Taiwan ({\textquoteleft}Aim for the Top University Project{\textquoteright} to National Taiwan University; 2011–2017), MOST, Taiwan (MOST 103-2325-B-002-025), NIH/ NHGRI grant U54HG003067, NIMH grants R01 MH085521 and R01 MH085560, and NHRI, Taiwan (NHRI-EX104-10432PI). P. Sklar acknowledges U01MH109536. B.J.M. acknowledges Australian NHMRC grant 496698. J. Lee acknowledges the National Medical Research Council Translational and Clinical Research Flagship Programme (grant number: NMRC/TCR/003/2008) and the National Medical Research Council under the Centre Grant Programme (grant number: NMRC/CG/004/2013). P.H. acknowledges funding support from the Medical Research Council (MR/L010305/1). S.X. acknowledges funding support from the Strategic Priority Research Program (XDB13040100) and Key Research Program of Frontier Sciences (QYZDJ-SSW-SYS009) of the Chinese Academy of Sciences, as well as the National Natural Science Foundation of China (NSFC; grants 91731303, 31525014 and 31771388), UK Royal Society–Newton Advanced Fellowship (NAF/R1/191094), Program of Shanghai Academic Research Leader (16XD1404700), National Key Research and Development Program (2016YFC0906403) and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01). P.F.S. acknowledges PGC funding from U01 MH109528 and U01 MH1095320. M.J.D. acknowledges NIH/NIMH 5U01MH109539-02. M.C.O.{\textquoteright}D. acknowledges funding from MRC (G0800509) and NIMH (reference: 1U01MH109514-01). S.Q. acknowledges the National Key Research and Development Program of China (2016YFC0905000 and 2016YFC0905002) and the Shanghai Key Laboratory of Psychotic Disorders (13dz2260500). K.S.H. acknowledges a grant from the National Research Foundation of Korea (2015R1A2A2A01002699), funded by the Ministry of Science, ICT and Future Planning. D.B.W. and S.G.S. acknowledge funding support from the NHMRC (grant 513861). W.Y. acknowledges the National Key Research and Development Program of China (2016YFC1307000), NSFC (81571313) and the Peking University Clinical Scientist Program, supported by {\textquoteleft}the Fundamental Research Funds for the Central Universities{\textquoteright} (BMU2019LCKXJ012). M.T. acknowledges R01 MH085560 (Expanding Rapid Ascertainment Networks of Schizophrenia Families in Taiwan). J. Liu acknowledges funding support from the Agency for Science, Technology and Research, Singapore. Xiancang Ma acknowledges (and was principal investigator on) the National NSFC Surface project (81471374). Y.S. acknowledges the National Key Research and Development Program of China (2016YFC0903402), NSFC (31325014, 81130022 and 81421061) and 973 Program (2015CB559100). H.H. acknowledges support from NIH K01DK114379, NIH R21AI139012, the Zhengxu and Ying He Foundation and the Stanley Center for Psychiatric Research. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = dec,
doi = "10.1038/s41588-019-0512-x",
language = "English",
volume = "51",
pages = "1670--1678",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "12",
}