Irritable bowel syndrome and migraine: evidence from Mendelian randomization analysis in the UK Biobank

ABSTRACT

Background

Irritable Bowel Syndrome (IBS) and Migraine are two diseases featuring high prevalence. Previous studies have suggested a relationship between IBS and migraine, although the causal association remains unclear. The authors sought to explore the causal association between IBS and migraine, and to show the importance of migraine prevention in IBS patients.

Methods

This study conducted a Mendelian randomization analysis to explore the association of IBS with migraine. Genetic association with migraine was acquired from the UK Biobank (UKB) genetic databases (cases: 1,072; controls: 360,122). The authors performed estimation using Inverse Variance Weighting (IVW), along with Maximum Likelihood, MR-RAPS, MR-Egger, and Weighted Median for sensitivity analysis. Considering possible bias, they also conducted polymorphism, heterogeneity, and directional analysis.

Results

The IVW estimation genetically predicted the causal association between IBS and migraine (OR = 1.09, 95% CI 1.01 to 1.17, p = 0.03). Neither statistical horizontal pleiotropy (MR Egger p = 0.42; MR-PRESSO p = 0.78) nor possible heterogeneity (IVW Q = 26.15, p = 0.80) was found. Reverse causation was also not detected (p steiger<0.01).

Conclusion

Mendelian randomization analysis supported a potential causal association between IBS and migraine, providing enlightenment for disease prevention and control.

KEYWORDS:

• Migraine
• irritable bowel syndrome
• Mendelian randomization
• epidemiology
• UK Biobank

Supplemental data

Supplemental data for this article can be accessed here.

Article Highlights

• Mendelian randomization analysis is a gene-based approach that can estimate the causal relationship with published Genome-Wide Association Studies summary data.

• Some observational studies have pointed out the association between Irritable Bowel Syndrome and Migraine (IBS).

• This Mendelian randomization first establishes the causal association between the two diseases from a genetic perspective.

• Patients and clinicians should attach importance to migraine-related symptoms in IBS.

• Treatments and palliative measures concerning IBS and migraine should be developed accordingly.

This box summarizes key points contained in the article.

Acknowledgments

The authors appreciate MRC Integrative Epidemiology Unit (https://gwas.mrcieu.ac.uk/) and Neale Lab (http://www.nealelab.is/uk-biobank) for the publicly available summary data. The authors thank the blogger (orange_milk_sugar, W Chen) for helping them with the methods and H. Chen (Zhejiang University) with the language editing.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Availability of data and materials

All data used for the analysis were derived from published GWAS data. Migraine data are available at https://gwas.mrcieu.ac.uk/datasets/ukb-d-G43/

IBS data are available at https://gwas.mrcieu.ac.uk/datasets/ukb-d-K58/

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Author contributions

J. Chen, X. Chen, and Y. Xie contributed to data acquisition, analysis, and writing. Y Sun helped analyze the data. X. Wang and T. Hesketh contributed to the project's design and manuscript revision. All authors approved the final version of the manuscript.

Article highlights

• Mendelian randomization analysis is a gene-based approach that can estimate the causal relationship with published Genome-Wide Association Studies summary data.

• Some observational studies have pointed out the association between Irritable Bowel Syndrome and Migraine (IBS).

• This Mendelian randomization first establishes the causal association between the two diseases from a genetic perspective.

• Patients and clinicians should attach importance to migraine-related symptoms in IBS.

• Treatments and palliative measures concerning IBS and migraine should be developed accordingly.

Additional information

Funding

This paper was supported by the National Natural Science Foundation of China (81970494) and the Key Project of Research and Development Plan of Hunan Province (2019SK2041).