Molecular mechanisms underlying psoriasis and depression: an integrated analysis using mendelian randomization, transcriptomics, and single-cell sequencing

Background Psoriasis, an immune-mediated systemic inflammatory disease affecting skin, vessels, and joints, often co-occurs with depression. Routine depression screening is vital, as mood disorders link to inflammation, visible lesions, and functional limitations. Methods The study integrated Mendelian randomization (MR), transcriptomics, and single-cell omics via public databases to explore comorbidity mechanisms. Results MR identified 340 psoriasis-related and 307 depression-related eQTL-gene associations; 9 intersected. LASSO found 4 key Genes ( MAP3K20, WARS2, TBXAS1, ABHD15 ), enriched in IL-17/NF-κB/FoxO pathways, cholesterol metabolism, and synaptic cycling. They correlated with immune infiltration, ferroptosis, and specific cell localization. Folic acid (from CTD) targeted 3 genes. Conclusion These 4 genes mediate comorbidity via inflammation, immune metabolism, and ferroptosis. Folic acid pathways have therapeutic value, laying a foundation for precision therapy.