Genetic associations between systemic lupus erythematosus and pulmonary arterial hypertension

Objective Epidemiological studies have found a close association between systemic lupus erythematosus (SLE) and pulmonary arterial hypertension (PAH). The aim of this study was to explore the genetic correlation, shared genetic structure, and potential mechanisms between SLE and PAH.Methods Based on the summary data of large - scale genome - wide association studies (GWAS), we evaluated the genetic correlation between SLE and PAH and conducted cross - trait analysis. SMR analysis was used to analyze potential drug targets, and functional annotation and tissue - specific analysis were used as supplementary methods to explore the potential association between the two.Results We found a significant local genetic correlation between SLE and PAH (P < 0.05/2495). A total of 113 possible SNP loci (P < 5×10–8) related to both SLE and PAH were identified. Based on FUMA, 14 risk SNPs associated with both SLE and PAH were identified. Further SMR analysis revealed 27 overlapping potential druggable genes between the two. Based on the stratified LD score regression (S - LDSC) method and FUMA, SNP loci were mainly enriched in skin, whole blood, and liver tissues, while genes showed significant enrichment in whole blood, brain tissue, fibroblasts, and spleen.Conclusion Our study demonstrated the genetic association and shared structure between SLE and PAH and preliminarily revealed the potential regulatory mechanisms.