Habitual sleep disturbances and migraine: a Mendelian randomization study

Iyas Daghlas, Angeliki Vgontzas, Yanjun Guo, Daniel I Chasman, Richa Saxena, International Headache Genetics Consortium, Thomas Folkmann Hansen (Medlem af forfattergruppering), Jes Olesen (Medlem af forfattergruppering), Ann-Louise Esserlind (Medlem af forfattergruppering), Mona Ameri Chalmer (Medlem af forfattergruppering), Lisette Kogelman (Medlem af forfattergruppering)

Abstract

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.

OriginalsprogEngelsk
TidsskriftAnnals of Clinical and Translational Neurology
Vol/bind7
Udgave nummer12
Sider (fra-til)2370-2380
Antal sider11
ISSN2328-9503
DOI
StatusUdgivet - okt. 2020

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