In a study published in Pharmacogenomics and Personalized Medicine, researchers conducted a case-control study and a bidirectional mendelian randomization (MR) analysis to ascertain whether insomnia is causally related to the development of migraine. The authors wrote that MR, which utilizes genetic variants associated with exposure variables as genetic instruments to infer the causality, can be a beneficial tool for evaluating the role of insomnia in migraine occurrence. The instrumental variables for insomnia were developed from the largest genome-wide association study of 1,331,010 participants, whereas the genetic instruments for migraine were available from the largest meta-analysis of migraine comprising 59,674 cases and 316,078 controls.

The researchers discovered that subjects with insomnia had a considerably greater risk of migraine (odds ratio [OR] = 4.29; 95% CI, 3.21-5.74, P <.001) compared with those without insomnia. The bidirectional two-sample MR analysis showed that insomnia was significantly correlated with higher risk of migraine (OR = 1.24; 95% CI, 1.11-1.38, P = 1.01x10-4), and the results were validated in the UK Biobank data. The study results showed no indication for directional pleiotropy effects as evaluated by the MR-Egger intercept (P >.05).

The authors acknowledged several limitations to their study, and these should be considered when interpreting the results. First, the researchers used self-reported insomnia complaints rather than objective measures owing to the complexity of trait measurement. Second, because collider bias remains an issue in MR analysis, the possible pleiotropy effect might be obscured by a small sample size. Third, due to the limitation of the genome-wide association study summary statistics data, stratified evaluations of the major migraine subtypes were not conducted. Lastly, the authors stated that overlapping samples in the two-sample MR analysis may cause the results to be overemphasized and that larger studies exploring migraine subtypes are warranted.

The researchers concluded that in their study heightened migraine risk was confined to subjects with a genetic predisposition to insomnia but that these findings nonetheless have potential implications for improving sleep quality to diminish the migraine burden.

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