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Background <p>Recent observational studies have revealed an inconclusive correlation between inflammatory bowel disease (IBD) and sepsis, accompanied by an uncertain understanding of the causal relationship between the two. To investigate the causality between IBD and sepsis, we employed a two-sample Mendelian randomization (MR) approach.</p> Methods <p>A genome-wide significant threshold (<i>P</i> &lt; 5 × 10<sup>–8</sup>) was achieved in order to identify single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for two types of IBD, such as Crohn's disease (CD) and ulcerative colitis (UC). Subsequently, the selected SNPs were assessed in relation to three categories of sepsis, namely sepsis, sepsis (critical care), and sepsis (28-day death in critical care). An inverse-variance weighted (IVW) estimation of MR was conducted, followed by sensitivity analysis on multiple dimensions.</p> Results <p>There was a significant association between genetic liability to CD (IVW: OR, 1.246; 95% CI, 1.090–1.423; <i>P</i> = 0.0012) with sepsis (28-day death in critical care), but not with sepsis (critical care) and sepsis. Whereas UC showed slightly, yet statistically insignificant, higher risk for sepsis (IVW: OR, 1.031; 95% CI, 0.988–1.064; <i>P</i> = 0.064).</p> Conclusion <p>Our study offers genetic evidence that supports a substantial causal relationship between CD and sepsis (28-day death in critical care). To enhance the specificity and objectivity of future research findings, it is recommended to specify the types of IBD and the severity of sepsis. Furthermore, the genetic risk loci related may become potential drug development targets.</p>

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Causal associations between inflammatory bowel disease and sepsis: a two-sample Mendelian randomization study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月17日

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  • Renyang Tong,
  • Ziting Liang,
  • Chengui Zhuo,
  • Xueyang Bai,
  • Ling Dao,
  • Lu Yu,
  • Ling Li,
  • Zhaohui Tong,
  • Youyou Du,
  • Longwei Xu

摘要

Background

Recent observational studies have revealed an inconclusive correlation between inflammatory bowel disease (IBD) and sepsis, accompanied by an uncertain understanding of the causal relationship between the two. To investigate the causality between IBD and sepsis, we employed a two-sample Mendelian randomization (MR) approach.

Methods

A genome-wide significant threshold (P < 5 × 10–8) was achieved in order to identify single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for two types of IBD, such as Crohn's disease (CD) and ulcerative colitis (UC). Subsequently, the selected SNPs were assessed in relation to three categories of sepsis, namely sepsis, sepsis (critical care), and sepsis (28-day death in critical care). An inverse-variance weighted (IVW) estimation of MR was conducted, followed by sensitivity analysis on multiple dimensions.

Results

There was a significant association between genetic liability to CD (IVW: OR, 1.246; 95% CI, 1.090–1.423; P = 0.0012) with sepsis (28-day death in critical care), but not with sepsis (critical care) and sepsis. Whereas UC showed slightly, yet statistically insignificant, higher risk for sepsis (IVW: OR, 1.031; 95% CI, 0.988–1.064; P = 0.064).

Conclusion

Our study offers genetic evidence that supports a substantial causal relationship between CD and sepsis (28-day death in critical care). To enhance the specificity and objectivity of future research findings, it is recommended to specify the types of IBD and the severity of sepsis. Furthermore, the genetic risk loci related may become potential drug development targets.