학술논문

Comparative genetic architectures of schizophrenia in East Asian and European populations
Document Type
article
Source
Nature Genetics. 51(12)
Subject
Genetics
Human Genome
Serious Mental Illness
Schizophrenia
Brain Disorders
Mental Health
Prevention
Aetiology
2.1 Biological and endogenous factors
Mental health
Good Health and Well Being
Asian People
Case-Control Studies
Asia
Eastern
Genetics
Population
Genome-Wide Association Study
Humans
Polymorphism
Single Nucleotide
White People
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Indonesia Schizophrenia Consortium
Genetic REsearch on schizophreniA neTwork-China and the Netherlands
Biological Sciences
Medical and Health Sciences
Developmental Biology
Language
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.