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.

中文翻译：

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东亚和欧洲人群精神分裂症的比较遗传结构。

精神分裂症是一种使人衰弱的精神疾病，全球范围内的终生风险约为 1%。大规模精神分裂症遗传学研究主要针对欧洲血统样本进行报告，可能遗漏了重要的生物学见解。在这里，我们报告了迄今为止东亚参与者的最大研究（22,778 例精神分裂症病例和 35,362 例对照），确定了 19 个基因位点中的 21 个全基因组显着关联。赋予精神分裂症风险的常见遗传变异在东亚和欧洲血统之间具有高度相似的影响（遗传相关性 = 0.98 ± 0.03），表明精神分裂症的遗传基础及其生物学在人群中广泛共享。一项包括来自东亚和欧洲血统的个体的固定效应荟萃分析在 176 个遗传位点（53 个新颖）中确定了 208 个显着关联。跨祖先精细定位减少了 44 个基因座中的候选因果变异集。当跨祖先转移时，多基因风险评分降低了性能，强调了包括足够的主要祖先群体样本以确保它们在人群中的普遍性的重要性。