Trans-Ancestry Psychiatric Genomics in Admixed Populations: Advances, Challenges, and Future Directions

Area of Science:

• Genetics
• Psychiatry
• Population Genetics

Background:

• Early genome-wide association studies (GWAS) for psychiatric disorders primarily focused on European populations.
• This limited the comprehensive understanding of genetic architecture across diverse ancestries.

Purpose of the Study:

• To synthesize current research on the shared and ancestry-specific genetic architecture of major psychiatric disorders.
• To highlight the implications of genetic diversity for psychiatric disorder research.

Main Methods:

• Review of multi-ancestry genome-wide association studies (GWAS).
• Analysis of trans-ancestral meta-analyses, fine-mapping studies, and polygenic risk score evaluations.
• Inclusion of local ancestry and rare/structural variant studies.

Main Results:

• Common genetic liability for psychiatric disorders is largely consistent across ancestries, indicated by high genetic correlations and shared biological pathways.
• Differences in locus transferability, fine-mapping resolution, and polygenic score performance are attributed to variations in linkage disequilibrium, allele frequencies, and local ancestry.
• Rare and structural variants play a significant role in ancestry-specific risk.

Conclusions:

• Psychiatric disorders exhibit a shared polygenic foundation within distinct ancestry-specific genomic contexts.
• Context-dependent penetrance influences disorder manifestation.
• Integrating diverse and admixed populations is essential for advancing biological discovery and ensuring equitable clinical translation in psychiatry.