Vanderbilt team finds 60 new IBD risk loci and 441 candidate genes in 63,415 cases

Researchers from Vanderbilt University and Vanderbilt University Medical Center (Nashville, USA) report a multi-ancestry genetic analysis of inflammatory bowel disease (IBD) in Nature Communications. A meta-analysis of genome-wide association studies (GWAS) covered 63,415 cases of European and East Asian ancestry and identified 60 previously unreported susceptibility loci doi.orgNature Communicationsdoi.orgOpen source ↗. The paper was published on 4 November 2026; the corresponding author is Xingyi Guo.

The authors state that they used genetic resources from earlier IBD GWAS, VA MVP, FinnGen, UKB, UKIBDGC and IIBDGC. The work is a statistical genetic study based on association data and gene expression, not a clinical trial.

From loci to genes

To move from associated loci to specific genes, the team combined several approaches: multi-ancestry transcriptome-wide association studies (TWAS), cell type-specific TWAS, and analyses of alternative splicing and alternative polyadenylation. The expression data came from RNA sequencing of normal colon tissue from 707 Europeans and 364 East Asians doi.orgNature Communicationsdoi.orgOpen source ↗.

This produced 441 candidate risk genes. Of these, 324 had not previously been implicated by GWAS or TWAS, and 291 of the 324 received further support from colocalization or summary-data-based Mendelian randomization analyses doi.orgNature Communicationsdoi.orgOpen source ↗.

Pathways and druggable genes

According to the authors, the identified genes converge on pathways central to IBD pathogenesis, for example immune regulation. More than half of the genes showed transcriptional dysregulation supported by single-cell and spatial omics analyses doi.orgNature Communicationsdoi.orgOpen source ↗.

The team also identified 44 druggable genes linked to 221 approved drugs or compounds in Phase II/III clinical development doi.orgNature Communicationsdoi.orgOpen source ↗. The material describes these as links between genes and compounds; it does not report testing of these compounds in IBD in this study.

The authors say the results deepen the understanding of IBD genetics and provide insights for future research relevant to precision medicine for the disease doi.orgNature Communicationsdoi.orgOpen source ↗.