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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Comparative genetic architectures of schizophrenia in East Asian and European populations
AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium
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 - Yue, Weihua
AU - Knight, Jo
PY - 2019/12/31
Y1 - 2019/12/31
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.
U2 - 10.1038/s41588-019-0512-x
DO - 10.1038/s41588-019-0512-x
M3 - Journal article
C2 - 31740837
VL - 51
SP - 1670
EP - 1678
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 12
ER -