Migraine, inflammatory bowel disease and celiac disease: A Mendelian randomization study
Welander NZ., Rukh G., Rask-Andersen M., Harder AVE., Gormley P., Anttila V., Winsvold BS., Palta P., Esko T., Pers TH., Farh KH., Cuenca-Leon E., Muona M., Furlotte NA., Kurth T., Ingason A., McMahon G., Ligthart L., Terwindt GM., Kallela M., Freilinger TM., Ran C., Gordon SG., Stam AH., Steinberg S., Borck G., Koiranen M., Quaye L., Adams HHH., Lehtimäki T., Sarin AP., Wedenoja J., Hinds DA., Buring JE., Schürks M., Ridker PM., Hrafnsdottir MG., Stefansson H., Ring SM., Hottenga JJ., Penninx BWJH., Färkkilä M., Artto V., Kaunisto M., Vepsäläinen S., Malik R., Heath AC., Madden PAF., Martin NG., Montgomery GW., Kurki M., Kals M., Mägi R., Pärn K., Hämäläinen E., Huang H., Byrnes AE., Franke L., Huang J., Stergiakouli E., Lee PH., Sandor C., Webber C., Cader Z., Muller-Myhsok B., Schreiber S., Meitinger T., Eriksson JG., Salomaa V., Heikkilä K., Loehrer E., Uitterlinden AG., Hofman A., van Duijn CM., Cherkas L., Pedersen LM., Stubhaug A., Nielsen CS., Männikö M., Mihailov E., Milani L., Göbel H., Esserlind AL., Christensen AF., Hansen TF., Werge T., Børte S., Cormand B., Eising E., Griffiths L., Hamalainen E., Hiekkala M., Kajanne R., Launer L., Lehtimaki T., Lessel D., Macaya A., Mangino M., Pedersen N., Posthuma D.
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.