Association Between Insomnia and Migraine Risk: A Case–Control and Bidirectional Mendelian Randomization Study

BACKGROUND: The causal relationship between insomnia and migraine is contradictory and no study has been carried out among the Chinese population to date. METHODS: In this case, we conducted a case–control study and a bidirectional mendelian randomization (MR) analysis to determine whether insomnia is causally related to the development of migraine. The instrumental variables for insomnia were derived from the largest genome-wide association study of 1,331,010 participants, while the genetic instruments for migraine were available from the largest meta-analysis of migraine with 59,674 cases and 316,078 controls. RESULTS: In case–control study, subjects with insomnia have significantly higher risk of migraine (OR=4.29, 95% CI: 3.21–5.74, P<0.001), compared with those without insomnia. The bidirectional two-sample MR analysis revealed that 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. The results showed no indication for directional pleiotropy effects as assessed by the MR-Egger intercept (P>0.05). CONCLUSION: Conclusively, our study highlighted that increased migraine risk was confined to subjects with a genetic pre-disposition to insomnia, and these findings had potential implications for improving the sleep quality to reduce the burden of migraine.