{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T01:57:07Z","timestamp":1784685427606,"version":"3.55.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2019s 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically predicted depression was associated with migraine (OR = 1.321, 95% CI: 1.184\u20131.473, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). Furthermore, risk factors insomnia was associated with migraine risk (OR = 1.766, 95% CI: 1.120\u20132.784, <jats:italic>p<\/jats:italic> = 0.014). The mediator insomnia accounted for 19.5% of the total effect of depression on migraine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2024.1326817","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T04:28:12Z","timestamp":1717129692000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Mediators of the association between depression and migraine: a mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Yang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuena","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s10194-010-0282-4","article-title":"Migraine and psychiatric comorbidity: a review of clinical findings","volume":"12","author":"Antonaci","year":"2011","journal-title":"J. headache pain"},{"key":"B2","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s10194-012-0479-9","article-title":"Depression and risk of transformation of episodic to chronic migraine","volume":"13","author":"Ashina","year":"2012","journal-title":"J. headache pain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S61","DOI":"10.1007\/s10072-009-0071-5","article-title":"Migraine and psychiatric disorders: comorbidities, mechanisms, and clinical applications","volume":"30","author":"Baskin","year":"2009","journal-title":"Neurological Sci. official J. 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