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. 2023 Mar 24;12(7):2482.
doi: 10.3390/jcm12072482.

Causal Link between Inflammatory Bowel Disease and Fistula: Evidence from Mendelian Randomization Study

Zongbiao Tan  1 , Shijie Zhu  2 , Chuan Liu  1 , Yang Meng  3 , Jiao Li  1 , Jixiang Zhang  1 , Weiguo Dong  1
Affiliations

Causal Link between Inflammatory Bowel Disease and Fistula: Evidence from Mendelian Randomization Study

Zongbiao Tan et al. J Clin Med. .

Abstract

Background: Previous observational studies have found that fistulas are common in Crohn's disease (CD) and less common in ulcerative colitis (UC). However, some patients have a fistula before diagnosis. Based on retrospective analysis, it was not possible to determine whether there was a bi-directional causal relationship between inflammatory bowel disease (IBD) and fistulas.

Methods: Data were extracted from the open GWAS database; 25,042 cases and 34,915 controls were included for IBD, and 6926 cases and 30,228 controls were included for fistula. Two-sample Mendelian randomization and multivariable Mendelian randomization were used in combination to determine the causal relationship between IBD and fistula.

Results: Forward MR showed that IBD increased the risk of colonic or urogenital fistula (FISTULA) (OR: 1.09, 95% CI: 1.05 to 1.13, p = 1.22 × 10-6), mainly associated with fissure and fistula of the anal and rectal regions (FISSANAL) (OR:1.10, 95% CI:1.06 to 1.14, p = 6.12 × 10-8), but not with fistulas involving the female genital tract (FEMGENFISTUL) (OR:0.97, 95% CI: 0.85 to 1.11, p = 0.669). Furthermore, both UC and CD increased the risk of FISTULA. However, after adjusting by MVMR, only CD increased the risk of FISTULA (OR: 1.06, 95% CI: 1.02 to 1.11, p = 0.004), and UC did not increase the risk of FISTULA (OR: 1.01, 95% CI: 0.95 to 1.06, p = 0.838). Reverse MR showed that fistulas did not increase the risk of IBD.

Conclusion: Our study confirms it is CD, rather than UC, that casually leads to an increased risk of fistula, but fistulas do not increase the risk of IBD.

Keywords: Mendelian randomization; fistula; genetic epidemiology; inflammatory bowel disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The workflow of this study.
Figure 2
Figure 2
Mendelian randomization (MR) results of IVW. Causal estimation of IBD effects on fistulas (IBD: inflammatory bowel disease; UC: ulcerative colitis; CD: Crohn’s disease; FISTULA: colonic or urogenital fistula; FISSANAL: fissure and fistula of anal and rectal region; FEMGENFISTUL: fistula involving female genital tract; NSNP: the number of single nucleotide polymorphisms used in MR analysis; OR: odds ratio; CI: confidence interval).
Figure 3
Figure 3
Multivariable Mendelian randomization (MVMR) results. Causal estimation of IBD subtype effects on fistulas (IBD: inflammatory bowel disease; UC: ulcerative colitis, CD: Crohn’s disease; FISTULA: colonic or urogenital fistula; FISSANAL: fissure and fistula of anal and rectal regions; FEMGENFISTUL: fistula involving female genital tract; NSNP: the number of single nucleotide polymorphisms used in MR analysis; OR: odds ratio; CI: confidence interval).
Figure 4
Figure 4
Mendelian randomization (MR) results of IVW. Causal estimation of fistula effects on IBD (IBD: inflammatory bowel disease; UC: ulcerative colitis; CD: Crohn’s disease; FISTULA: colonic or urogenital fistula; FISSANAL: fissure and fistula of anal and rectal regions; FEMGENFISTUL: fistula involving female genital tract; NSNP: the number of single nucleotide polymorphisms used in MR analysis; OR: odds ratio; CI: confidence interval).
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References

    1. Ng S.C., Shi H.Y., Hamidi N., Underwood F.E., Tang W., Benchimol E.I., Panaccione R., Ghosh S., Wu J.C.Y., Chan F.K.L., et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies. Lancet. 2017;390:2769–2778. doi: 10.1016/S0140-6736(17)32448-0. - DOI - PubMed
    1. Jairath V., Feagan B.G. Global burden of inflammatory bowel disease. Lancet Gastroenterol. Hepatol. 2020;5:2–3. doi: 10.1016/S2468-1253(19)30358-9. - DOI - PubMed
    1. Kaur M., Dalal R.L., Shaffer S., Schwartz D.A., Rubin D.T. Inpatient Management of Inflammatory Bowel Disease-Related Complications. Clin. Gastroenterol. Hepatol. 2020;18:1346–1355. doi: 10.1016/j.cgh.2019.12.040. - DOI - PubMed
    1. Rieder F., Zimmermann E.M., Remzi F.H., Sandborn W.J. Crohn’s disease complicated by strictures: A systematic review. Gut. 2013;62:1072–1084. doi: 10.1136/gutjnl-2012-304353. - DOI - PMC - PubMed
    1. Geldof J., Iqbal N., LeBlanc J.F., Anandabaskaran S., Sawyer R., Buskens C., Bemelman W., Gecse K., Lundby L., Lightner A.L., et al. Classifying perianal fistulising Crohn’s disease: An expert consensus to guide decision-making in daily practice and clinical trials. Lancet Gastroenterol. Hepatol. 2022;7:576–584. doi: 10.1016/S2468-1253(22)00007-3. - DOI - PubMed

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