BACKGROUND
Ulcerative 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.
METHODS
We 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.
RESULTS
Our 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.
CONCLUSION
These 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.
Guo Liu, Na Wu, Qing-Hua Luo et al.· Human Immunology· 0 citations
Background Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. Methods We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. Results Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy = 1.0573 × 10 − ⁴), adipose tissue (pCauchy = 1.5366 × 10 − ⁴), and liver (pCauchy = 1.0167 × 10 − ³). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy = 1.7823 × 10 − ⁴), with no significant liver or epidermal enrichment. Conclusion Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.
Guo Liu, Feng-Juan Gong, Guan-Hu Yang et al.· PLoS ONE· 0 citations
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