Risk relationship between inflammatory bowel disease and urolithiasis: A two-sample Mendelian randomization study

PLoS One. 2024 Apr 9;19(4):e0301545. doi: 10.1371/journal.pone.0301545. eCollection 2024.

Abstract

Background: The causal genetic relationship between common parenteral manifestations of inflammatory bowel disease (IBD) and urolithiasis remains unclear because their timing is difficult to determine. This study investigated the causal genetic association between IBD and urolithiasis using Mendelian randomization (MR) based on data from large population-based genome-wide association studies (GWASs).

Methods: A two-sample MR analysis was performed to assess the potential relationship between IBD and urolithiasis. Specific single nucleotide polymorphism data were obtained from GWASs, including IBD (n = 59957) and its main subtypes, Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data on urolithiasis (n = 218792) were obtained from different GWAS studies. A random-effects model was analyzed using inverse-variance weighting, MR-Egger, and weighted medians.

Results: Genetic predisposition to IBD and the risk of urolithiasis were significantly associated [odds ratio (OR), 1.04 (95% confidence interval [CI], 1.00-.08), P = 0.01]. Consistently, the weighted median method yielded similar results [OR, 1.06 (95% CI, 1.00-1.12), P = 0.02]. The MR-Egger method also demonstrated comparable findings [OR, 1.02 (95% CI, 0.96-1.08), P = 0.45]. Both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and urolithiasis. CD was strongly associated with it in its subtype analysis [OR, 1.04 (95% CI, 1.01-1.07), P = 0.01], and UC was also causally associated with urolithiasis, although the association was not significant [OR, 0.99 (95% CI, 0.95-1.03), P = 0.71].

Conclusion: A unidirectional positive causal correlation was identified between IBD and urolithiasis, with varying degrees of association observed among the different subtypes of IBD. Recognizing the increased incidence of urolithiasis in patients with IBD is crucial in clinical practice. Early detection and surveillance of IBD, improved patient awareness, adoption of preventive strategies, and promotion of collaborative efforts among healthcare providers regarding treatment methodologies are vital for improving patient outcomes.

MeSH terms

  • Colitis, Ulcerative* / complications
  • Colitis, Ulcerative* / genetics
  • Crohn Disease* / complications
  • Crohn Disease* / genetics
  • Genome-Wide Association Study
  • Humans
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / genetics
  • Mendelian Randomization Analysis
  • Urolithiasis* / epidemiology
  • Urolithiasis* / genetics

Grants and funding

This work was supported by Key Research and Development Program of Tibet Autonomous Region (Grant No.XZ202001ZY0059G to Bin Zhu). The funders had no role in the study design, data collection, or analysis but provided the initial writing of the manuscript and the supervision, review, and editorial advice of subsequent articles. In addition to this, “There was no additional external funding received for this study”.