Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study
Open Access
- 27 January 2023
- journal article
- research article
- Published by Wiley in Headache: The Journal of Head and Face Pain
- Vol. 63 (5), 642-651
- https://doi.org/10.1111/head.14470
Abstract
ObjectiveTo assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. BackgroundMigraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition. MethodsLinkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed. ResultsMigraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99-1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99-1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96-1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79-1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00-1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92-0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02-1.29, p = 0.025). However, the results were not significant after multiple testing correction. ConclusionsWe found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.Keywords
Funding Information
- Åke Wiberg Stiftelse
- Svenska Läkaresällskapet (SLS‐935235)
- Svenska Sällskapet för Medicinsk Forskning (SSMF 30072019)
- Vetenskapsrådet (2019‐01066)
This publication has 40 references indexed in Scilit:
- An atlas of genetic correlations across human diseases and traitsNature Genetics, 2015
- Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populationsNature Genetics, 2015
- Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regressionInternational Journal of Epidemiology, 2015
- UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old AgePLoS Medicine, 2015
- LD Score regression distinguishes confounding from polygenicity in genome-wide association studiesNature Genetics, 2015
- Migraine Associated with Gastrointestinal Disorders: Review of the Literature and Clinical ImplicationsFrontiers in Neurology, 2014
- Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related lociNature Genetics, 2013
- Prevalence of Migraine in Patients With Celiac Disease and Inflammatory Bowel DiseaseHeadache: The Journal of Head and Face Pain, 2012
- Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac diseaseNature Genetics, 2011
- Multiple common variants for celiac disease influencing immune gene expressionNature Genetics, 2010