Transcriptome-Wide Association Studies of 81 traits in 79,294 Korean individuals

Genome-wide association studies (GWAS) have linked genetic loci to complex traits, but their interpretation is limited by linkage disequilibrium (LD) and difficulties in identifying causal genes. Transcriptome-wide association studies (TWAS) address these challenges by leveraging predicted gene expression to map genomic risk regions. However, TWAS reference panels are predominantly based on European ancestry, restricting their utility for other populations. Here, we developed a Korean-specific whole blood reference panel for transcriptome imputation and performed TWAS, examining 81 traits in 79,294 Korean individuals. This Korean panel showed improved predictive performance over the GTEx reference panel, identifying 348 significant gene-trait associations (Bonferroni-corrected P  < 0.05), including 232 novel associations, compared to 180 associations with GTEx. Furthermore, pathway analysis revealed unique biological processes in the Korean model, offering insights into diseases such as thyroid disease and type 2 diabetes. Drug repurposing identified promising candidates, including clopidogrel for angina and vorinostat for fatty liver. These findings highlight the value of population-specific approaches in genetic research.