Genetic analyses identify shared genetic components related to autoimmune and cardiovascular diseases

Objectives Autoimmune diseases (ADs) play a significant and intricate role in the onset of cardiovascular diseases (CVDs). Our study aimed to elucidate the shared genetic etiology between Ads and CVDs. Methods We conducted genome-wide pleiotropy analyses to investigate the genetic foundation comprehensively and shared etiology of six ADs and six CVDs. We analyze the genetic architecture and genetic overlap between these traits. Then, SNP-level functional annotation identified significant genomic risk loci and potential causal variants. Gene-level analyses explored shared pleiotropic genes, followed by pathway enrichment analyses to elucidate underlying biological mechanisms. Finally, we assess potential causal pathways between ADs and CVDs. Results Despite negligible overall genetic connections, our results revealed a significant genetic overlap between ADs and CVDs, indicating a complex shared genetic architecture spread throughout the genome. The shared loci implicated several genes, including ATXN2 , BRAP , SH2B3 , ALDH2 (all located at 12q24.11-12), RNF123 , MST1R , RBM6 , and UBA7 (all located at 3p21.31), all of which are protein-coding genes. Top biological pathways enriched with these shared genes were related to the immune system and intracellular signal transduction. Conclusions The extensive genetic overlap with mixed effect directions between ADs and CVDs indicates a complex genetic relationship between these diseases. It suggests overlapping genetic risk may contribute to shared pathophysiological and clinical characteristics and may guide clinical treatment and management.