Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study.

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, 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. CONCLUSIONS: We 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.

Association between migraine prevalence, treatment with proton-pump inhibitors and CYP2C19 phenotypes in UK Biobank.

Proton-pump inhibitors (PPIs) are used to suppress gastric acid secretion in several gastrointestinal conditions. While these drugs are generally well tolerated, their long-term use may be associated with different adverse effects, including migraine. We analyzed the association between treatment with PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole) and migraine prevalence in the UK Biobank cohort through a cross-sectional analysis (using baseline data for 468,280 participants, 16,390 of whom had migraine) and a longitudinal analysis (including 145,007 participants with no migraine at baseline, of whom 3786 had probable migraine without aura [MWOA] and 9981 probable migraine with aura [MWA] or both MWOA and MWA at an average follow-up time of 10.06 years). We also evaluated the modulating role of the metabolizer phenotype of CYP2C19, the major enzyme involved in PPI clearance. Treatment with PPIs was associated with higher migraine prevalence at baseline (odds ratio [OR] = 1.25, p < 0.0001). CYP2C19 rapid metabolizer phenotype was associated with lower prevalence of migraine exclusively in participants treated with PPIs (OR = 0.89, p = 0.029). In addition, treatment with PPIs was associated with higher incidence of both probable MWOA (OR = 1.24, p = 0.002) and MWA (OR = 1.43, p < 0.0001) at follow-up. Treatment with PPIs and CYP2C19 poor metabolizer status were associated with higher incidence of probable chronic migraine exclusively in men. Our results suggest a significant association between treatment with PPIs and migraine in this large population-based cohort and support a potential relevant role of gender and CYP2C19 phenotype.

Migraine as a risk factor for mixed symptoms of peripartum depression and anxiety in late pregnancy: A prospective cohort study.

BACKGROUND: Migraine has been identified as a risk factor for peripartum depression. However, little is known about the contribution of anxiety to this association or potential changes throughout the peripartum period. METHODS: In a sample of 4,831 women from the Biology, Affect, Stress, Imaging and Cognition cohort in Sweden, participants were asked about history of migraine prior to pregnancy. The participants completed the Edinburgh Postnatal Depression Scale (EPDS) at gestational weeks 17 and 32 and postpartum week 6. Multinomial logistic regression analyses were used to assess associations between migraine and symptoms of depression, anxiety or mixed depression and anxiety, while adjusting for potential confounders. RESULTS: In crude estimates, migraine was associated with separate and mixed symptoms of depression and anxiety at most time points. After adjustments, migraine was associated with anxiety at week 17 (adjusted odds ratio: 1.69; 95% confidence interval: 1.11-2.54) and with mixed depression and anxiety at week 32 (adjusted odds ratio: 1.45; 95% confidence interval: 1.06-1.99). None of the other associations remained statistically significant after adjustments. LIMITATIONS: Migraine history was self-reported. Symptoms of depression and anxiety were based on the screening tool EPDS and not on clinical diagnoses. CONCLUSIONS: The results demonstrate that migraine may be a risk factor for anxiety in mid- pregnancy and mixed symptoms of peripartum depression and anxiety in late pregnancy. Inflammatory and hormonal factors may underlie the association between migraine, depression and anxiety across the peripartum period.

Migraine and gastrointestinal disorders in middle and old age: A UK Biobank study.

INTRODUCTION: Migraine is a prevalent condition causing a substantial level of disability worldwide. Despite this, the pathophysiological mechanisms are not fully understood. Migraine often co-occurs with gastrointestinal disorders, but the direction of a potential causal link is unclear. The aim of this project was to investigate the associations between migraine and several gastrointestinal disorders in the same cohort in order to determine the relative strengths of these associations. METHODS: This cross-sectional study examined whether migraine is associated with irritable bowel syndrome (IBS), peptic ulcers, Helicobacter pylori (HP) infections, celiac disease, Crohn's disease and ulcerative colitis. Baseline data covering 489,753 UK Biobank participants (migraine group: n = 14,180) were analyzed using Pearson's chi-square tests and adjusted binary logistic regression models. RESULTS: Migraine was significantly associated with IBS (odds ratio [OR] 2.24, 95% confidence interval [CI] 2.08-2.40, p <.001) and peptic ulcers (OR 1.55, 95% CI 1.35-1.77, p <.001). Migraine was not associated with HP infection (OR 1.34, 95% CI 1.04-1.73, p = .024), celiac disease (OR 1.29, 95% CI 1.04-1.60, p = .023), Crohn's disease (OR 1.08, 95% CI 0.80-1.45, p = .617) or ulcerative colitis (OR 1.00, 95% CI 0.79-1.27, p = .979) after adjusting for multiple testing. CONCLUSIONS: Migraine was associated with IBS and peptic ulcers in this large population-based cohort. The associations with HP infection, celiac disease, Crohn's disease, and ulcerative colitis did not reach significance, suggesting a weaker link between migraine and autoimmune gastrointestinal conditions or HP infection.