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<p>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 <i>Butyricicoccus</i>, showed a causal effect on VHD and GERD. This study underscores that gastrointestinal-VHD comorbidity may stem from shared genetic pathways and microbial influences.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月22日

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  • Jing Xu,
  • Zeye Liu,
  • Lianlian Wu,
  • Fengbo Pei,
  • Hong Jiang,
  • Chen Cheng,
  • Weixian Yang,
  • Jiansong Yuan,
  • Renato Polimanti,
  • Yuejin Yang

摘要

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.