Comparative genetic architectures of schizophrenia in East Asian and European populations

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Indonesia Schizophrenia Consortium, Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN)

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1670-1678
Number of pages9
JournalNature Genetics
Volume51
Issue number12
DOIs
Publication statusPublished - 18 Nov 2019

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Schizophrenia
Genetic Loci
Population
Psychiatry
Meta-Analysis
Genome

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Schizophrenia Working Group of the Psychiatric Genomics Consortium, Indonesia Schizophrenia Consortium, & Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN) (2019). Comparative genetic architectures of schizophrenia in East Asian and European populations. Nature Genetics, 51(12), 1670-1678. https://doi.org/10.1038/s41588-019-0512-x
Schizophrenia Working Group of the Psychiatric Genomics Consortium ; Indonesia Schizophrenia Consortium ; Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN). / Comparative genetic architectures of schizophrenia in East Asian and European populations. In: Nature Genetics. 2019 ; Vol. 51, No. 12. pp. 1670-1678.
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Schizophrenia Working Group of the Psychiatric Genomics Consortium, Indonesia Schizophrenia Consortium & Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN) 2019, 'Comparative genetic architectures of schizophrenia in East Asian and European populations' Nature Genetics, vol. 51, no. 12, pp. 1670-1678. https://doi.org/10.1038/s41588-019-0512-x

Comparative genetic architectures of schizophrenia in East Asian and European populations. / Schizophrenia Working Group of the Psychiatric Genomics Consortium; Indonesia Schizophrenia Consortium; Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN).

In: Nature Genetics, Vol. 51, No. 12, 18.11.2019, p. 1670-1678.

Research output: Contribution to journalArticle

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Schizophrenia Working Group of the Psychiatric Genomics Consortium, Indonesia Schizophrenia Consortium, Genetic REsearch on schizophreniA neTwork-China and the Netherlands (GREAT-CN). Comparative genetic architectures of schizophrenia in East Asian and European populations. Nature Genetics. 2019 Nov 18;51(12):1670-1678. https://doi.org/10.1038/s41588-019-0512-x