Expressive

rs11230827 (RAB3IL1): Schizophrenia Risk Variant

Key takeaways

  • rs11230827 near RAB3IL1 is a genome-wide significant schizophrenia risk locus identified in one of the largest trans-ancestry psychiatric GWAS studies conducted.
  • The study combined over 22,000 East Asian schizophrenia cases with European cohorts, finding 208 significant loci including 53 novel ones.
  • Schizophrenia risk effects are nearly identical in East Asian and European populations, with a genetic correlation of 0.98.
  • Risk scores trained on one ancestry group perform less accurately in another, a key limitation to keep in mind.

Key takeaways

  • rs11230827 near RAB3IL1 is a genome-wide significant schizophrenia risk locus identified in one of the largest trans-ancestry psychiatric GWAS studies conducted.
  • The study combined over 22,000 East Asian schizophrenia cases with European cohorts, finding 208 significant loci including 53 novel ones.
  • Schizophrenia risk effects are nearly identical in East Asian and European populations, with a genetic correlation of 0.98.
  • Risk scores trained on one ancestry group perform less accurately in another, a key limitation to keep in mind.

What the research says A large trans-ancestry genome-wide association study (GWAS) of schizophrenia combined 22,778 East Asian cases and 35,362 controls from 20 sample collections across East Asia with European ancestry data, identifying 208 genome-wide significant associations in 176 loci, including 53 novel loci. Common variants conferring schizophrenia risk show highly similar effects in East Asian and European samples (genetic correlation rg = 0.98 +/- 0.03), indicating broadly shared biology. Trans-ancestry fine-mapping refined the candidate causal variant sets in 44 loci, improving the precision of genetic mapping for this disorder.

Reported associations

  • Schizophrenia: rs11230827, in the region of RAB3IL1 (RAB3 GTPase-interacting-like 1 - a gene involved in vesicle trafficking pathways), was identified as a genome-wide significant locus for schizophrenia risk in a trans-ancestry meta-analysis combining East Asian (22,778 cases, 35,362 controls) and European ancestry cohorts, as part of 208 significant loci (53 novel) identified in the study.

Evidence quality The source study is among the largest East Asian schizophrenia GWAS to date, with 22,778 cases and 35,362 controls across 20 sample collections, using a two-stage design with quality control, imputation, and fixed-effect meta-analysis with inverse-variance weighting. The high genetic correlation between East Asian and European samples (rg = 0.98 +/- 0.03) provides cross-ancestry support for identified loci, and trans-ancestry fine-mapping improved causal variant resolution in 44 loci. A key limitation is that polygenic risk scores (statistical scores that aggregate effects across many variants) performed approximately 45% as accurately in East Asian samples as in European samples when derived from European-only GWAS, indicating that ancestry-matched training data is important for generalizability across populations. No PMID was supplied for this study in the provided source metadata, so inline citation links are omitted.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11230827?

rs11230827 is a genetic variant located near the RAB3IL1 gene that has been associated with schizophrenia risk in a large trans-ancestry GWAS spanning East Asian and European populations.

What does the RAB3IL1 gene do?

RAB3IL1 stands for RAB3 GTPase-interacting-like 1. The research available focuses on its genetic association with schizophrenia risk and does not provide detail on its specific molecular function.

Is rs11230827 linked to schizophrenia?

Yes. rs11230827 near RAB3IL1 reached genome-wide significance for schizophrenia in a trans-ancestry meta-analysis that identified 208 significant loci in total, 53 of which were novel findings not previously reported.

Does this variant have the same effect in all ancestries?

The source study found a genetic correlation of 0.98 between East Asian and European populations, suggesting the risk effects are very similar. However, polygenic risk scores trained on one ancestry group perform notably less accurately when applied to another.

How large was the study that identified this variant?

The East Asian component included 22,778 schizophrenia cases and 35,362 controls from 20 sample collections across East Asia. A trans-ancestry meta-analysis also incorporated European ancestry participants, making this one of the largest studies of schizophrenia genetics to date.