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

Early genome-wide association studies (GWAS) of psychiatric disorders were conducted predominantly in European populations, limiting the understanding of genetic architecture across ancestries.

To summarize current evidence on shared and ancestry-specific genetic architecture in major psychiatric disorders.

We reviewed findings from multi-ancestry GWAS, trans-ancestral meta-analyses, fine-mapping, polygenic risk score, and local ancestry studies.

Common-variant liability is largely shared across ancestries, with high genetic correlations and overlapping biological pathways. However, locus transferability, fine-mapping resolution, and polygenic score performance differ because of variation in linkage disequilibrium, allele frequencies, environmental exposures, and local ancestry. Rare and structural variants further contribute to ancestry-specific risk.

Psychiatric disorders are characterized by a shared polygenic substrate embedded within ancestry-specific genomic architecture and context-dependent penetrance. Future studies should integrate diverse and admixed populations to improve biological discovery and equitable clinical translation.