Study Reveals Potential Causal Relationship Between Insomnia and Migraine


New study findings indicate individuals genetically predisposed to insomnia have a higher chance of suffering from migraine.

Individuals genetically predisposed to insomnia have an increased risk of migraine, according to study results published in Pharmacogenomics and Personalized Medicine. Findings did not show those suffering migraine were more likely to report insomnia.

Both migraine and sleep disorders are common conditions that impact quality of life of patients around the world, and although the relationship between insomnia and migraine has been evaluated in previous studies, findings are largely inconsistent, researchers wrote.

To determine whether insomnia is causally related to development of migraine, the investigators conducted a case-control study and bidirectional Mendelian randomization (MR) analysis.

MR was selected for use, as the tool “utilizes genetic variants associated with exposure variables as genetic instruments to infer the causality” and “is rarely affected by confounding bias and reverse causation due to the random assortment of genetic variants at conception,” they explained.

Data were gleaned from the largest genome-wide association study (GWAS) of 1,331,010 participants. Genetic instruments for migraine were collected from the largest meta-analysis of migraineurs, which included 59,674 patients and 31, 078 controls; both cohorts were made up of Chinese individuals.

Migraine incidence was measured via a diagnostic interview and structured questionnaire based on International Classification of Headache Disorders, 3rd edition, diagnostic criteria.

No significant differences related to age, gender, and body mass index were found between migraineurs and controls. However, migraineurs did report a higher percentage of family history of migraine and drinking habits.

Analyses revealed:

  • Patients with insomnia have significantly higher risk of migraine (adjusted odds ratio [OR] 4.29; 95% CI, 3.21-5.74; P <.001) compared with those without insomnia
  • Both those with insomnia sometimes (OR, 3.51; 95% CI, 2.47-4.98; P <.001) and those with usual insomnia (OR, 5.42; 95% CI, 3.78-7.76; P <.001) have a higher risk of migraine
  • The bidirectional 2-sample MR analysis showed insomnia was significantly associated with higher risk of migraine (OR, 1.24; 95% CI, 1.11-1.38; P = 1.01×10-4), and the results were validated in the UK Biobank data
  • There was no indication for directional pleiotropy effects as assessed by the MR-Egger intercept (P >.05); however, sensitivity analyses by MR-Egger did not validate the findings of the inverse-variance weighted (IVW) method
  • Using the IVW method, no significant causal relationship was found between genetically predicted migraine and insomnia risk (OR, 1.01; 95% CI, 1.00-1.02; P = .159); results also showed no indication for directional pleiotropy effects as assessed by the MR-Egger intercept (P >.05)

“A bidirectional 2-sample MR analysis was conducted and revealed that insomnia was causally related to the development of migraine. Collectively, our study highlights insomnia as a potentially modifiable risk factor for migraine,” the researchers wrote.

The inclusion of self-reported insomnia complaints as opposed to objective measures in the case-control study marks a limitation to the analysis, while “collider bias remains an issue in MR analysis, and the possible pleiotropy effect might be concealed by small sample size,” the authors cautioned.

In addition, stratified analyses of the major migraine subtypes were not carried out, and overlapping samples in the 2-sample MR analysis may have led to overestimated results.

Overall, “we observed that insomnia was significantly associated with higher risk of migraine. Both epidemiological study and MR analysis suggested that increased migraine risk was confined to subjects with a genetic predisposition to insomnia,” the researchers concluded.

“Further research should be directed towards exploring the molecular and cellular mechanisms underlying the effect of insomnia on increasing the likelihood of migraine. Nonetheless, these findings have potential implications for improving the sleep quality to reduce the burden of migraine.”


Chu S, Wu Z, Wu Z, Wu J, Qian Y. Association between insomnia and migraine risk: a case-control and bidirectional Mendelian randomization study. Pharmgenomics Pers Med. Published online August 13, 2021. doi:10.2147/PGPM.S305780

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