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Exploring the Genetic Relationship Between Migraine Subtypes, Depression And Anxiety Using Polygenic Scores

Doppenberg AC, Nyholt DR, Martin NC, Wray NR, Hickie I, Olsen CM, Whiteman DC, Thomas JT et al.

2026

16,532 participants

Abstract

Migraine is a disabling neurological disorder that frequently co-occurs with depression and anxiety. While prior research suggests a genetic association between these conditions, little is known about the genetic relationships underlying specific migraine subtypes. Bivariate genetic correlations between migraine with depression and anxiety were estimated using Linkage-Disequilibrium Score Regression (LDSC), drawing on publicly available large-scale Genome-Wide Association Study data for these traits. In addition, PGS were constructed using the same data and applied to two target cohorts for out-of-sample prediction of migraine and its subtypes. These were a depression-enriched cohort ( Australian Genetics of Depression Study ; N=12,601), and an unselected population cohort ( QSkin Study of Sun and Health ; N=16,532). Migraine subtypes were defined according to standard criteria and comprised a broad migraine without aura phenotype and three nested subtypes: migraine with aura, and chronic migraine with and without aura. We found significant genetic correlations between migraine and depression ( r g =0.29), as well as between migraine and anxiety ( r g =0.32). Across both cohorts, Migraine ( OR ≈1.35) and Depression PGS ( OR ≈1.12) were significantly associated with all measures of migraine and its subtypes. Depression PGS remained significantly associated with all non-chronic migraine subtypes after controlling for migraine and anxiety PGS, suggesting an independent…

How strong is the evidence?

Evidence Hub reads this as a cohort study. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 16,532 participants or records.

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