Multi-ancestry genome-wide and transcriptome-wide association analyses identify new risk loci and genes for inflammatory bowel disease

Multi-ancestry GWAS meta-analyses in 63,415 Europeans and East Asians identify 60 previously unreported inflammatory bowel disease susceptibility loci, expanding the known genetic architecture.

• Why it matters: IBD genetics still leaves much heritable risk unexplained, and new loci and genes are needed to refine biological mechanisms and support precision-medicine research.
• What they did: The study integrated multi-ancestry TWAS, cell type-specific TWAS, alternative splicing, and alternative polyadenylation using RNA-seq from normal colon tissues (707 Europeans, 364 East Asians) to nominate 441 candidate risk genes.
• The result: Among these, 324 were not previously implicated by GWAS or TWAS, with 291 further supported by colocalization or summary-data-based Mendelian randomization, and 44 druggable genes linked to 221 approved or Phase II/III compounds.