TY - JOUR

T1 - Habitual sleep disturbances and migraine

T2 - a Mendelian randomization study

AU - Daghlas, Iyas

AU - Vgontzas, Angeliki

AU - Guo, Yanjun

AU - Chasman, Daniel I.

AU - Saxena, Richa

AU - Pers, Tune H

AU - International Headache Genetics Consortium

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1002/acn3.51228

DO - 10.1002/acn3.51228

M3 - Journal article

C2 - 33125193

AN - SCOPUS:85102213760

VL - 7

SP - 2370

EP - 2380

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

SN - 2328-9503

IS - 12

ER -