Integrated multi-omics analysis reveals common genetic architecture between ulcerative colitis and psoriasis.

BACKGROUNDUlcerative colitis (UC) and psoriasis (PS) are both chronic inflammatory disorders that frequently occur together in clinical settings. Nevertheless, the common genetic basis and biological mechanisms underlying this comorbidity remain insufficiently understood.

METHODSWe integrated genome-wide association study summary data with UC and PS single-cell transcriptomic data and performed reference-atlas-based spatial mapping using an E16.5 mouse embryonic spatial transcriptomic atlas to comprehensively investigate their shared genetic relationships, polygenic overlap, tissue-specific enrichment, reference-atlas-based anatomical enrichment patterns, disease-relevant cell populations, and potential candidate genes.

RESULTSOur analyses demonstrated a significant common genetic foundation between UC and PS at both the global and local genomic scales, together with marked polygenic sharing. Enrichment and reference-atlas-based analyses suggested that UC- and PS-associated genetic signals converged on immune-, intestinal- and epidermis-related tissue contexts. Integration of the four-component descriptive prioritization framework identified T cells among the prioritized candidate cell types in both diseases, with concordant support from the CELLECT-S-LDSC and CELLECT-MAGMA components. In addition, several candidate genes, including PARK7, C2orf74, PUS10, and TNFSF15, were prioritized, among which PARK7 showed significant case-control differential expression in T-cell subsets in both UC and PS.

CONCLUSIONThese findings suggest that UC and PS may share genetic and biological features across tissue and cellular contexts. This study provides a hypothesis-generating framework for investigating their comorbidity and highlights candidate genes with potential therapeutic relevance.