Unveiling the shared etiology between gastrointestinal disorders and valvular heart diseases through a genome-wide pleiotropy study

This study explores the genetic link between gastrointestinal disorders and valvular heart disease (VHD), aiming to clarify shared mechanisms through a genome-wide pleiotropy analysis. We assessed the genetic correlation between six gastrointestinal disorders-including GERD, IBS, PUD, IBD, Crohn's disease, and ulcerative colitis-and VHD, employing methods like linkage disequilibrium score regression and pleiotropic analysis under a composite null hypothesis. Our results show significant genetic correlations, particularly with GERD (rg = 0.211), IBS (rg = 0.23), and PUD (rg = 0.21). Fifteen variants and 64 genes were identified with pleiotropic effects, implicating pathways associated with other conditions like heart defects and dermatitis. Additionally, gut microbiota, specifically Butyricicoccus, showed a causal effect on VHD and GERD. This study underscores that gastrointestinal-VHD comorbidity may stem from shared genetic pathways and microbial influences.