Association between multiple sclerosis and inflammatory bowel diseases: a Mendelian randomization study_Chinese Journal of Evidence-Based Medicine

Authors：

XU Ting , YUAN Mingyang ,  HOU Deren

Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China;

Corresponding author：

HOU Deren, Email: hou0718@126.com

Keywords：

Mendelian randomization; Multiple sclerosis; Inflammatory bowel disease; Causal association

DOI：

10.7507/1672-2531.202311156

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To conduct a two-sample Mendelian randomization (MR) study to assess the bidirectional causal relationship between multiple sclerosis and inflammatory bowel disease. Methods We performed two-sample bidirectional MR analysis using publicly available genome-wide association study (GWAS) data. The primary analysis method used was the inverse variance weighted (IVW) method, with MR-Egger weighted median as a supplementary analysis. Sensitivity analyses were conducted. Results IVW, weighted median, and weighted mode all supported a causal relationship between multiple sclerosis and an increased risk of ulcerative colitis (OR=1.07, 95%CI 1.01 to 1.13, P=0.018), while no association was found between multiple sclerosis and Crohn's disease. Sensitivity analyses suggested that the study results were not affected by pleiotropy. Conclusion Genetic predisposition to multiple sclerosis is associated with an elevated risk of developing ulcerative colitis but not Crohn’s disease.

Citation： XU Ting, YUAN Mingyang, HOU Deren. Association between multiple sclerosis and inflammatory bowel diseases: a Mendelian randomization study. Chinese Journal of Evidence-Based Medicine, 2024, 24(8): 893-898. doi: 10.7507/1672-2531.202311156 Copy

1.	Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol, 2019, 26(1): 27-40.
2.	Koch-Henriksen N, Magyari M. Apparent changes in the epidemiology and severity of multiple sclerosis. Nat Rev Neurol, 2021, 17(11): 676-688.
3.	GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol, 2019, 18(5): 459-480.
4.	Compston A, Coles A. Multiple sclerosis. Lancet, 2008, 372(9648): 1502-1517.
5.	Henderson RD, Bain CJ, Pender MP. The occurrence of autoimmune diseases in patients with multiple sclerosis and their families. J Clin Neurosci, 2000, 7(5): 434-437.
6.	Konen FF, Möhn N, Witte T, et al. Treatment of autoimmunity: the impact of disease-modifying therapies in multiple sclerosis and comorbid autoimmune disorders. Autoimmun Rev, 2023, 22(5): 103312.
7.	Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol, 2014, 20(1): 91-99.
8.	Kimura K, Hunter SF, Thollander MS, et al. Concurrence of inflammatory bowel disease and multiple sclerosis. Mayo Clin Proc, 2000, 75(8): 802-806.
9.	Alkhawajah MM, Caminero AB, Freeman HJ, et al. Multiple sclerosis and inflammatory bowel diseases: what we know and what we would need to know. Mult Scler, 2013, 19(3): 259-265.
10.	Wang X, Wan J, Wang M, et al. Multiple sclerosis and inflammatory bowel disease: a systematic review and meta-analysis. Ann Clin Transl Neurol, 2022, 9(2): 132-140.
11.	Sekula P, Del Greco M F, Pattaro C, et al. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol, 2016, 27(11): 3253-3265.
12.	Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med, 2008, 27(8): 1133-1163.
13.	Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet, 2018, 50(5): 693-698.
14.	Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol, 2013, 178(7): 1177-1184.
15.	Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol, 2015, 44(2): 512-525.
16.	Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol, 2016, 40(4): 304-314.
17.	Bowden J, Del Greco MF, Minelli C, et al. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med, 2017, 36(11): 1783-1802.
18.	Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res, 2017, 26(5): 2333-2355.
19.	Nabizadeh F, Azizi A, Hejrati L, et al. Multiple sclerosis and ulcerative colitis: a systematic review and meta-analysis. Mult Scler J Exp Transl Clin, 2023, 9(3): 20552173231186516.
20.	Yang Y, Musco H, Simpson-Yap S, et al. Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases. Nat Commun, 2021, 12(1): 5641.
21.	Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet, 2012, 380(9853): 1606-1619.
22.	Sun Y, Zhang Z, Zheng CQ, et al. Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: a review. World J Gastroenterol, 2021, 27(22): 2963-2978.
23.	Maddur MS, Miossec P, Kaveri SV, et al. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol, 2012, 181(1): 8-18.
24.	Karagkouni A, Alevizos M, Theoharides TC. Effect of stress on brain inflammation and multiple sclerosis. Autoimmun Rev, 2013, 12(10): 947-953.
25.	Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun, 2016, 7: 12015.
26.	Miljković Đ, Jevtić B, Stojanović I, et al. ILC3, a central innate immune component of the gut-brain axis in multiple sclerosis. Front Immunol, 2021, 12: 657622.
27.	Camara-Lemarroy CR, Metz L, Meddings JB, et al. The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics. Brain, 2018, 141(7): 1900-1916.

1. Dobson R, Giovannoni G. Multiple sclerosis - a review. Eur J Neurol, 2019, 26(1): 27-40.
2. Koch-Henriksen N, Magyari M. Apparent changes in the epidemiology and severity of multiple sclerosis. Nat Rev Neurol, 2021, 17(11): 676-688.
3. GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol, 2019, 18(5): 459-480.
4. Compston A, Coles A. Multiple sclerosis. Lancet, 2008, 372(9648): 1502-1517.
5. Henderson RD, Bain CJ, Pender MP. The occurrence of autoimmune diseases in patients with multiple sclerosis and their families. J Clin Neurosci, 2000, 7(5): 434-437.
6. Konen FF, Möhn N, Witte T, et al. Treatment of autoimmunity: the impact of disease-modifying therapies in multiple sclerosis and comorbid autoimmune disorders. Autoimmun Rev, 2023, 22(5): 103312.
7. Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol, 2014, 20(1): 91-99.
8. Kimura K, Hunter SF, Thollander MS, et al. Concurrence of inflammatory bowel disease and multiple sclerosis. Mayo Clin Proc, 2000, 75(8): 802-806.
9. Alkhawajah MM, Caminero AB, Freeman HJ, et al. Multiple sclerosis and inflammatory bowel diseases: what we know and what we would need to know. Mult Scler, 2013, 19(3): 259-265.
10. Wang X, Wan J, Wang M, et al. Multiple sclerosis and inflammatory bowel disease: a systematic review and meta-analysis. Ann Clin Transl Neurol, 2022, 9(2): 132-140.
11. Sekula P, Del Greco M F, Pattaro C, et al. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol, 2016, 27(11): 3253-3265.
12. Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med, 2008, 27(8): 1133-1163.
13. Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet, 2018, 50(5): 693-698.
14. Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol, 2013, 178(7): 1177-1184.
15. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol, 2015, 44(2): 512-525.
16. Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol, 2016, 40(4): 304-314.
17. Bowden J, Del Greco MF, Minelli C, et al. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med, 2017, 36(11): 1783-1802.
18. Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res, 2017, 26(5): 2333-2355.
19. Nabizadeh F, Azizi A, Hejrati L, et al. Multiple sclerosis and ulcerative colitis: a systematic review and meta-analysis. Mult Scler J Exp Transl Clin, 2023, 9(3): 20552173231186516.
20. Yang Y, Musco H, Simpson-Yap S, et al. Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases. Nat Commun, 2021, 12(1): 5641.
21. Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet, 2012, 380(9853): 1606-1619.
22. Sun Y, Zhang Z, Zheng CQ, et al. Mucosal lesions of the upper gastrointestinal tract in patients with ulcerative colitis: a review. World J Gastroenterol, 2021, 27(22): 2963-2978.
23. Maddur MS, Miossec P, Kaveri SV, et al. Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies. Am J Pathol, 2012, 181(1): 8-18.
24. Karagkouni A, Alevizos M, Theoharides TC. Effect of stress on brain inflammation and multiple sclerosis. Autoimmun Rev, 2013, 12(10): 947-953.
25. Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun, 2016, 7: 12015.
26. Miljković Đ, Jevtić B, Stojanović I, et al. ILC3, a central innate immune component of the gut-brain axis in multiple sclerosis. Front Immunol, 2021, 12: 657622.
27. Camara-Lemarroy CR, Metz L, Meddings JB, et al. The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics. Brain, 2018, 141(7): 1900-1916.

Chinese Journal of Evidence-Based Medicine

Association between multiple sclerosis and inflammatory bowel diseases: a Mendelian randomization study

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content