Stratified shared genetic architecture of IBD and RA: an integrated analysis from polygenic overlap to directional heterogeneity

Despite modest genome-wide correlation, IBD and RA share a high degree of polygenic risk, and the apparent paradox is explained by mixed effect directions of shared variants. These results provide a stratified view of their shared genetic architecture and offer new insights into common immunological pathways contributing to comorbidity. As the GWAS datasets were predominantly of European ancestry, the generalizability of these findings to non-European populations remains uncertain, validation in ancestrally diverse cohorts is needed.