TY - JOUR
T1 - Comparative genetic architectures of schizophrenia in East Asian and European populations
AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium
AU - Indonesia Schizophrenia Consortium
AU - Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN)
AU - Lam, Max
AU - Chen, Chia Yen
AU - Li, Zhiqiang
AU - Martin, Alicia R.
AU - Bryois, Julien
AU - Ma, Xixian
AU - Gaspar, Helena
AU - Ikeda, Masashi
AU - Benyamin, Beben
AU - Brown, Brielin C.
AU - Liu, Ruize
AU - Zhou, Wei
AU - Guan, Lili
AU - Kamatani, Yoichiro
AU - Kim, Sung Wan
AU - Kubo, Michiaki
AU - Kusumawardhani, Agung A.A.A.
AU - Liu, Chih Min
AU - Ma, Hong
AU - Periyasamy, Sathish
AU - Takahashi, Atsushi
AU - Xu, Zhida
AU - Yu, Hao
AU - Zhu, Feng
AU - Chen, Wei J.
AU - Faraone, Stephen
AU - Glatt, Stephen J.
AU - He, Lin
AU - Hyman, Steven E.
AU - Hwu, Hai Gwo
AU - McCarroll, Steven A.
AU - Neale, Benjamin M.
AU - Sklar, Pamela
AU - Wildenauer, Dieter B.
AU - Yu, Xin
AU - Zhang, Dai
AU - Mowry, Bryan J.
AU - Lee, Jimmy
AU - Holmans, Peter
AU - Xu, Shuhua
AU - Sullivan, Patrick F.
AU - Ripke, Stephan
AU - O’Donovan, Michael C.
AU - Daly, Mark J.
AU - Qin, Shengying
AU - Sham, Pak
AU - Iwata, Nakao
AU - Hong, Kyung S.
AU - Schwab, Sibylle G.
AU - Ma, Xiancang
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85075373505
U2 - 10.1038/s41588-019-0512-x
DO - 10.1038/s41588-019-0512-x
M3 - 文章
C2 - 31740837
AN - SCOPUS:85075373505
SN - 1061-4036
VL - 51
SP - 1670
EP - 1678
JO - Nature Genetics
JF - Nature Genetics
IS - 12
ER -