Conflict of Interest: No conflict.
The Shared Genetics of Migraine and Anxious Depression
Article first published online: 3 NOV 2010
© 2010 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 50, Issue 10, pages 1549–1560, November/December 2010
How to Cite
Ligthart, L., Nyholt, D. R., Penninx, B. W.J.H. and Boomsma, D. I. (2010), The Shared Genetics of Migraine and Anxious Depression. Headache: The Journal of Head and Face Pain, 50: 1549–1560. doi: 10.1111/j.1526-4610.2010.01705.x
Financial support: This study was supported by grants from The Netherlands Organisation for Scientific Research, and the Centre for Medical Systems Biology (NWO-CMSB), Spinozapremie (NWO/SPI 56-464-14192), Borderline Personality Disorder Research Foundation, genome-wide analyses of European twin and population cohorts (EU/QLRT-2001-01254), resolving cause and effect in the association between regular exercise and psychological well-being (NWO-MW 904-61-19). Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org; NWO 480-05-003).
- Issue published online: 3 NOV 2010
- Article first published online: 3 NOV 2010
- Accepted for publication April 12, 2010.
Objectives.— To investigate (1) whether shared genetic factors influence migraine and anxious depression; (2) whether the genetic architecture of migraine depends on anxious depression; (3) whether the association between migraine and anxious depression is causal.
Background.— Migraine and anxious depression frequently occur together, but little is known about the mechanisms causing this association.
Methods.— A twin study was conducted to model the genetic architecture of migraine and anxious depression and the covariance between them. Anxious depression was also added to the model as a moderator variable to examine whether anxious depression affects the genetic architecture of migraine. Causal models were explored with the co-twin control method.
Results.— Modest but significant phenotypic (rP = 0.28), genetic (rG = 0.30), and nonshared environmental (rE = 0.26) correlations were found between the 2 traits. Interestingly, the heritability of migraine depended on the level of anxious depression: the higher the anxious depression score, the lower the relative contribution of genetic factors to the individual differences in migraine susceptibility. The observed risk patterns in discordant twins are most consistent with a bidirectional causal relationship.
Conclusions.— These findings confirm the genetic association between migraine and anxious depression and are consistent with a syndromic association between the 2 traits. This highlights the importance of taking comorbidity into account in genetic studies of migraine, especially in the context of selection for large-scale genotyping efforts. Genetic studies may be most effective when migraine with and without comorbid anxious depression are treated as separate phenotypes.