Journal Article

Habitual sleep disturbances and migraine: a Mendelian randomization study

Anttila, Verneri, Nielsen, Christopher S., Webber, Caleb, Olesen, Jes, Färkkilä, Markus, Mihailov, Evelin, Adams, Hieab H. H., Kubisch, Christian, Winsvold, Bendik S., Daghlas, Iyas, Farh, Kai‐How, Schürks, Markus, Muona, Mikko, Stefansson, Kari, Kallela, Mikko, Ikram, M. Arfan, Smith, George Davey, Sandor, Cynthia, Hinds, David A., Uitterlinden, Andre G., Boomsma, Dorret I., Esko, Tonu, Hrafnsdottir, Maria Gudlaug, Belin, Andrea C., Kaprio, Jaakko, Martin, Nicholas G., Järvelin, Marjo‐Riitta, Terwindt, Gisela M., Mägi, Reedik, Zwart, John‐Anker, Sarin, Antti‐Pekka, Muller‐Myhsok, Bertram, Wedenoja, Juho, Byrnes, Andrea E., Stergiakouli, Evie, Ferrari, Michel D., Kaunisto, Mari, Eriksson, Johan G., Pedersen, Linda M., Buring, Julie E., Quaye, Lydia, Cuenca‐Leon, Ester, Palotie, Aarno, Dichgans, Martin, Heath, Andrew C., Artto, Ville, Stefansson, Hreinn, Werge, Thomas, Pärn, Kalle, Aromaa, Arpo J., Kurth, Tobias, Kurki, Mitja I., Vgontzas, Angeliki, Ligthart, Lannie, van Duijn, Cornelia M., Montgomery, Grant W., Pers, Tune H., Huang, Hailiang, Männikkö, Minna, Palta, Priit, Schreiber, Stefan, Gordon, Scott

2020

Overview

Objective Sleep disturbances are associated with increased risk of migraine, however the extent of shared underlying biology and the direction of causal relationships between these traits is unclear. Delineating causality between sleep patterns and migraine may offer new pathophysiologic insights and inform subsequent intervention studies. Here, we used genetic approaches to test for shared genetic influences between sleep patterns and migraine, and to test whether habitual sleep patterns may be causal risk factors for migraine and vice versa. Methods To quantify genetic overlap, we performed genome‐wide genetic correlation analyses using genome‐wide association studies of nine sleep traits in the UK Biobank (n ≥ 237,627), and migraine from the International Headache Genetics Consortium (59,674 cases and 316,078 controls). We then tested for potential causal effects between sleep traits and migraine using bidirectional, two‐sample Mendelian randomization. Results Seven sleep traits demonstrated genetic overlap with migraine, including insomnia symptoms (rg = 0.29, P < 10−31) and difficulty awakening (rg = 0.11, P < 10−4). Mendelian randomization analyses provided evidence for potential causal effects of difficulty awakening on risk of migraine (OR [95% CI] = 1.37 [1.12–1.68], P = 0.002), and nominal evidence that liability to insomnia symptoms increased the risk of migraine (1.09 [1.02–1.16], P = 0.02). In contrast, there was minimal evidence for an effect of migraine liability on sleep patterns or disturbances. Interpretation These data support a shared genetic basis between several sleep traits and migraine, and support potential causal effects of difficulty awakening and insomnia symptoms on migraine risk. Treatment of sleep disturbances may therefore be a promising clinical intervention in the management of migraine.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adult / Biobanks / Causality / Comorbidity / Consortia / Databases, Factual / Genome-Wide Association Study / Genomes / Headaches / Health risk assessment / Humans / Insomnia / Mendelian Randomization Analysis / Migraine / Migraine Disorders - etiology / Migraine Disorders - genetics / Sleep / Sleep Initiation and Maintenance Disorders - complications / Sleep Initiation and Maintenance Disorders - genetics / Sleep Wake Disorders - complications / Sleep Wake Disorders - genetics / Software / United Kingdom