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Comparative genetic architectures of schizophrenia in East Asian and European populations
By
Max Lam,
Chia-Yen Chen,
Zhiqiang Li,
Alicia R. Martin,
Julien Bryois,
Xixian Ma,
Helena 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,
Qiang Wang,
Zhida Xu,
Hao Yu,
Feng Zhu,
Psychiatric Genomics Consortium - Schizophrenia Working Group,
Indonesia Schizophrenia Consortium,
Genetic REsearch on schizophreniA neTwork-China and Netherland (GREAT-CN),
Wei J. Chen,
Stephen Faraone,
Stephen J. Glatt,
Lin He,
Steven E. Hyman,
Hai-Gwo Hwu,
Tao Li,
Steven McCarroll,
Benjamin M Neale,
Pamela Sklar,
Dieter 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 Sham,
Nakao Iwata,
Kyung S. Hong,
Sibylle G Schwab,
Weihua Yue,
Ming Tsuang,
Jianjun Liu,
Xiancang Ma,
René S. Kahn,
Yongyong Shi,
Hailiang Huang
Posted 17 Oct 2018
bioRxiv DOI: 10.1101/445874
(published DOI: 10.1038/s41588-019-0512-x)
Schizophrenia is a severe psychiatric disorder with a lifetime risk of about 1% world-wide. Most large schizophrenia genetic studies have studied people of primarily European ancestry, potentially missing important biological insights. Here we present a study of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide significant schizophrenia associations in 19 genetic loci. Over the genome, the common genetic variants that confer risk for schizophrenia have highly similar effects in those of East Asian and European ancestry (rg=0.98), indicating for the first time that the genetic basis of schizophrenia and its biology are broadly shared across these world populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries revealed 208 genome-wide significant schizophrenia associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping more precisely isolated schizophrenia causal alleles in 70% of these loci. Despite consistent genetic effects across populations, polygenic risk models trained in one population have reduced performance in the other, highlighting the importance of including all major ancestral groups with sufficient sample size to ensure the findings have maximum relevance for all populations.
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