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ORIGINAL RESEARCH article

Front. Genet.
Sec. Statistical Genetics and Methodology
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1326817

Mediators of the association between depression levels and migraine: a Mendelian randomization study

Provisionally accepted
Yang Li Yang Li 1Ge Luo Ge Luo 1Xuena Wang Xuena Wang 1Liwang Zhou Liwang Zhou 1Hui Liu Hui Liu 1Yang Zhang Yang Zhang 1Min Yan Min Yan 1,2*
  • 1 Department of Anesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
  • 2 Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, China

The final, formatted version of the article will be published soon.

    Background: An association between depression and migraine has been reported in observational studies; however, conventional observational studies are prone to bias. This study aims to investigate the causal relationship between depression and migraine and to quantify the mediating effects of known risk factors. Methods: We applied two-sample Mendelian randomization and utilized single nucleotide polymorphisms as genetic instruments for exposure (depression) and mediators (sleep traits). We utilized summary data on genome-wide association studies for depression, sleep-related traits mediators and migraine. For depression, genome-wide association studies (depression) were utilized as a test cohort for the primary analysis. Moreover, genome-wide association studies (major depressive disorder) were utilized to test the stability of the results for the validation cohort. IVW and MR-Egger regression were applied to test the heterogeneity, and Cochran’s Q statistics were calculated to quantitatively evaluate the heterogeneity. MR-PRESSO analyses were utilized to examine and correct possible horizontal pleiotropy through removing outliers, and leave-one-out analyses were utilized to identify outlier SNPs. Results: Genetically predicted depression was associated with migraine (OR = 1.321, 95% CI: 1.184-1.473, P < 0.001). Furthermore, risk factors insomnia was associated with migraine risk (OR = 1.766, 95% CI: 1.120-2.784, P = 0.014). The mediator insomnia accounted for 19.5% of the total effect of depression on migraine. Conclusion: These results support a potential causal effect of depression on migraine, partly mediated by insomnia. Therefore, the enhancement of sleep quality and difficulty in falling asleep may reduce the migraine burden occasioned by depression.

    Keywords: causality, Depression, Mendelian Randomization Analysis, Migraine Disorders, Risk factors

    Received: 28 Feb 2024; Accepted: 13 May 2024.

    Copyright: © 2024 Li, Luo, Wang, Zhou, Liu, Zhang and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Min Yan, Department of Anesthesiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.