Causal effect of psoriasis on aortic valve stenosis: a two-sample Mendelian randomization study

Area of Science:

• Cardiovascular Epidemiology
• Dermatology
• Genetics

Background:

• Epidemiological studies suggest a link between psoriasis and increased aortic valve stenosis (AS) risk.
• The precise impact of psoriasis on AS progression and the underlying mechanisms require further investigation.

Purpose of the Study:

• To investigate the causal relationship between psoriasis and AS using Mendelian randomization (MR).
• To identify potential biological mechanisms connecting psoriasis and AS.

Main Methods:

• A two-sample MR analysis utilized summary statistics from GWAS for psoriasis and AS.
• Gene expression, pathway enrichment, and protein-protein interaction analyses were performed.
• Transcriptional profiling of AS patients identified key genes and immune cell involvement.

Main Results:

• A significant causal relationship was found, with psoriasis genetic predisposition increasing AS risk (OR: 1.46).
• Fifteen hub genes, including HLA-C, HLA-B, ISG15, IFIT3, and MX2, and immune-related pathways were identified.
• Genes such as ISG15, MX2, OAS3, OASL, IFI6, and EPSTI1 showed higher expression in AS patients, implicating adaptive immunity.

Conclusions:

• This study provides strong evidence for a causal link between psoriasis and AS.
• Identified hub genes and immune pathways are crucial in the pathogenesis of both psoriasis and AS.