Migraine, Inflammatory Bowel Disease and Celiac Disease

A Mendelian Randomization Study

Nike Zoe Welander MSc; Gull Rukh PhD; Mathias Rask-Andersen PhD; Aster V. E. Harder MSc, MD; Arn M. J. M. van den Maagdenberg PhD; Helgi Birgir Schiöth PhD; Jessica Mwinyi MD, PhD

Disclosures

Headache. 2023;63(5):642-651.

Abstract and Introduction

Abstract

Objective: To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.

Background: Migraine 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.

Methods: Linkage 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.

Results: Migraine 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,

Table 1. Genetic correlations between gastrointestinal conditions and migraine.
Gastrointestinal condition	r _G	SE	Z	p	Intercept	SE
IBD	0.05	0.03	1.60	0.110	0.01	0.01
Crohn's disease	0.01	0.01	0.50	0.621	0.00	0.00
Ulcerative colitis	0.02	0.36	0.56	0.577	0.01	0.01
Celiac disease²⁶	−0.02	0.67	−0.33	0.742	0.01	0.03
Celiac disease²⁷	0.01	0.06	0.19	0.846	0.00	0.01

Note: Genetic correlations based on results from linkage disequilibrium score regression analyses. For celiac disease, two separate sets of summary statistics were used. The references to these publications are provided using superscript numerals. The intercept for the genetic covariance and its SE are also provided. The intercept is expected to be zero in the absence of confounding factors affecting both traits.
Abbreviations: IBD, inflammatory bowel disease; r_G , genetic correlation; SE, standard error; Z, Z score.