Associations of Modifiable Factors with Risk of Irritable Bowel Syndrome

Overview

Journal Front Nutr

Specialty Nutritional Sciences

Date 2024 Jul 16

PMID 39010855

Authors

Ying Chen

Hong Yang

Jie Song

Weiwei Chen

Ke Liu

Bin Liu

Peiyang Luo

Xiaohui Sun

Zhixing He

Yingying Mao

Ding Ye

Affiliations

Soon will be listed here.

Abstract

Background: Modifiable factors were found to be associated with the risk of irritable bowel syndrome (IBS) in observational studies, but whether these associations are causal is uncertain. We conducted a Mendelian randomization (MR) study to systematically explore the causal associations of modifiable factors with IBS.

Methods: Summary-level statistical data for IBS was obtained from a genome-wide association study (GWAS) meta-analysis of UK Biobank (40,548 cases and 293,220 controls) and the international collaborative Bellygenes initiative (12,852 cases and 139,981 controls). Genetic instruments associated with the exposures at the genome-wide significance ( < 5 × 10) level were selected from previous GWASs. Mendelian randomization was performed using inverse-variance weighted (IVW) method, supplemented with several sensitivity analyses to evaluate potentially causal relationships between identified contributing factors and IBS. Furthermore, we applied another database from FinnGen (8,116 IBS cases and 276,683 controls) to testify the reliability of the significant associations.

Results: Seven convincing modifiable factors were significantly associated with IBS after correction for multiple testing. Genetically predicted smoking initiation (OR = 1.12, 95% CI = 1.06-1.18, = 1.03 × 10), alcohol consumption (OR = 0.47, 95% CI = 0.34-0.64, = 3.49 × 10), sedentary behavior (OR = 1.17, 95% CI = 1.07-1.28, = 4.02 × 10), chronotype (OR = 0.92, 95% CI = 0.88-0.96, = 4.42 × 10), insomnia (OR = 1.19, 95% CI = 1.15-1.24, = 7.59 × 10), education (OR = 0.80, 95% CI = 0.74-0.88, = 5.34 × 10), and visceral adiposity (OR = 1.15, 95% CI = 1.06-1.24, = 7.96 × 10). We additionally identified several suggestive factors, including serum magnesium, serum phosphorus, physical activity, lifetime smoking, intelligence, lean body mass, and body mass index (BMI). After pooling the effect estimates from FinnGen, the associations remained significant except for chronotype.

Conclusion: This MR analysis verified several modifiable risk factors for IBS, thus prevention strategies for IBS should be considered from multiple perspectives on these risk factors.

Citing Articles

The burden of irritable bowel syndrome and functional dyspepsia in Poland: a cross-sectional study from West Pomeranian Voivodship.

Krynicka P, Kaczmarczyk M, Skonieczna-Zydecka K, Cembrowska-Lech D, Podsiadlo K, Dabkowski K BMC Gastroenterol. 2025; 25(1):8.

PMID: 39789471 PMC: 11715971. DOI: 10.1186/s12876-024-03580-6.

References

El-Salhy M, Ostgaard H, Gundersen D, Hatlebakk J, Hausken T . The role of diet in the pathogenesis and management of irritable bowel syndrome (Review). Int J Mol Med. 2012; 29(5):723-31. DOI: 10.3892/ijmm.2012.926. View

Chen J, Chen X, Xie Y, Sun Y, Wang X, Hesketh T . Irritable bowel syndrome and migraine: evidence from Mendelian randomization analysis in the UK Biobank. Expert Rev Gastroenterol Hepatol. 2021; 15(10):1233-1239. DOI: 10.1080/17474124.2021.1949290. View

Eijsbouts C, Zheng T, Kennedy N, Bonfiglio F, Anderson C, Moutsianas L . Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders. Nat Genet. 2021; 53(11):1543-1552. PMC: 8571093. DOI: 10.1038/s41588-021-00950-8. View

Tu Q, Heitkemper M, Jarrett M, Buchanan D . Sleep disturbances in irritable bowel syndrome: a systematic review. Neurogastroenterol Motil. 2016; 29(3). DOI: 10.1111/nmo.12946. View

Sun Y, Chen X, Wang S, Deng M, Xie Y, Wang X . Gluten-free Diet Reduces the Risk of Irritable Bowel Syndrome: A Mendelian Randomization Analysis. Front Genet. 2021; 12:684535. PMC: 8660079. DOI: 10.3389/fgene.2021.684535. View

Savin Z, Kivity S, Yonath H, Yehuda S . Smoking and the intestinal microbiome. Arch Microbiol. 2018; 200(5):677-684. DOI: 10.1007/s00203-018-1506-2. View

Cremonini F, Camilleri M, Zinsmeister A, Herrick L, Beebe T, Talley N . Sleep disturbances are linked to both upper and lower gastrointestinal symptoms in the general population. Neurogastroenterol Motil. 2008; 21(2):128-35. PMC: 2642899. DOI: 10.1111/j.1365-2982.2008.01181.x. View

Fass R, Fullerton S, Tung S, Mayer E . Sleep disturbances in clinic patients with functional bowel disorders. Am J Gastroenterol. 2000; 95(5):1195-2000. DOI: 10.1111/j.1572-0241.2000.02009.x. View

Burgess S, Butterworth A, Thompson S . Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013; 37(7):658-65. PMC: 4377079. DOI: 10.1002/gepi.21758. View

10.

Liu H, Zou Y, Kan Y, Li X, Zhang Y . Prevalence and Influencing Factors of Irritable Bowel Syndrome in Medical Staff: A Meta-Analysis. Dig Dis Sci. 2022; 67(11):5019-5028. PMC: 8853241. DOI: 10.1007/s10620-022-07401-2. View

11.

Orr W, Fass R, Sundaram S, Scheimann A . The effect of sleep on gastrointestinal functioning in common digestive diseases. Lancet Gastroenterol Hepatol. 2020; 5(6):616-624. DOI: 10.1016/S2468-1253(19)30412-1. View

12.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

13.

Freuer D, Linseisen J, Meisinger C . Asthma and the risk of gastrointestinal disorders: a Mendelian randomization study. BMC Med. 2022; 20(1):82. PMC: 8925069. DOI: 10.1186/s12916-022-02283-7. View

14.

Peters H, de Vries W, vanBerge-Henegouwen G, Akkermans L . Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract. Gut. 2001; 48(3):435-9. PMC: 1760153. DOI: 10.1136/gut.48.3.435. View

15.

Sirri L, Grandi S, Tossani E . Smoking in Irritable Bowel Syndrome: A Systematic Review. J Dual Diagn. 2017; 13(3):184-200. DOI: 10.1080/15504263.2017.1322226. View

16.

Black C, Ford A . Global burden of irritable bowel syndrome: trends, predictions and risk factors. Nat Rev Gastroenterol Hepatol. 2020; 17(8):473-486. DOI: 10.1038/s41575-020-0286-8. View

17.

Roth B, Larsson E, Ohlsson B . Poor intake of vitamins and minerals is associated with symptoms among patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2022; 37(7):1253-1262. PMC: 9544605. DOI: 10.1111/jgh.15830. View

18.

Summa K, Voigt R, Forsyth C, Shaikh M, Cavanaugh K, Tang Y . Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation. PLoS One. 2013; 8(6):e67102. PMC: 3688973. DOI: 10.1371/journal.pone.0067102. View

19.

Lundstrom O, Manjer J, Ohlsson B . Smoking is associated with several functional gastrointestinal symptoms. Scand J Gastroenterol. 2016; 51(8):914-22. DOI: 10.1080/00365521.2016.1174878. View

20.

Reding K, Cain K, Jarrett M, Eugenio M, Heitkemper M . Relationship between patterns of alcohol consumption and gastrointestinal symptoms among patients with irritable bowel syndrome. Am J Gastroenterol. 2013; 108(2):270-6. PMC: 3697482. DOI: 10.1038/ajg.2012.414. View