Molecular mechanisms underlying psoriasis and depression: an integrated analysis using mendelian randomization,...

Area of Science:

• Immunology
• Genetics
• Pharmacology

Background:

• Psoriasis is a systemic inflammatory disease frequently co-occurring with depression.
• Depression screening is crucial due to links between mood disorders, inflammation, and functional impairment in psoriasis patients.

Purpose of the Study:

• To investigate the underlying genetic and molecular mechanisms of psoriasis-depression comorbidity.
• To identify potential therapeutic targets for precision medicine.

Main Methods:

• Utilized Mendelian randomization (MR), transcriptomics, and single-cell omics.
• Integrated data from public databases to analyze gene associations.
• Employed LASSO regression to identify key genes.

Main Results:

• Identified 340 psoriasis-related and 307 depression-related eQTL-gene associations, with 9 intersecting.
• Discovered four key genes (MAP3K20, WARS2, TBXAS1, ABHD15) enriched in inflammatory and metabolic pathways.
• Observed correlations between these genes, immune infiltration, ferroptosis, and specific cell types. Folic acid targeted three genes.

Conclusions:

• The four identified genes mediate psoriasis-depression comorbidity through inflammation, immune metabolism, and ferroptosis.
• Folic acid pathways present therapeutic value, supporting precision therapy development.