Exploring the causal relationship between PAH and some autoimmune diseases using bidirectional Mendelian...

Area of Science:

• Genetics
• Immunology
• Cardiovascular Medicine

Background:

• The relationship between pulmonary arterial hypertension (PAH) and autoimmune diseases is not fully understood.
• Investigating causal links can reveal shared underlying mechanisms and inform treatment strategies.

Purpose of the Study:

• To assess the bidirectional causal associations between PAH and several autoimmune diseases.
• To identify common molecular pathways and key genes involved in the comorbidity of PAH and rheumatoid arthritis (RA).

Main Methods:

• Utilized bidirectional Mendelian randomization (MR) analysis with genome-wide association summary statistics.
• Performed sensitivity analyses (heterogeneity, pleiotropy, leave-one-out) for robust findings.
• Conducted transcriptome analysis, including GO, KEGG enrichment, and protein-protein interaction network analysis.

Main Results:

• A significant bidirectional causal relationship was identified between PAH and RA.
• Enrichment analysis highlighted the chemokine pathway and other inflammation-related signaling pathways as common mechanisms.
• Identified core genes (CCL5, CCL9, VCAM1) and key transcription factors (GATA1, JUN, RELA) in the disease association.

Conclusions:

• A bidirectional positive causal link exists between PAH and RA.
• Dysregulation of the chemokine pathway and inflammation-related signaling pathways are critical in the progression of both PAH and RA.
• Findings provide insights into the molecular basis of PAH-RA comorbidity.