You are here

Cephalalgia DOI:10.1177/0333102417690111

Epigenetic DNA methylation changes associated with headache chronification: A retrospective case-control study.

Publication TypeJournal Article
Year of Publication2018
AuthorsWinsvold, BS, Palta, P, Eising, E, Page, CM, van den Maagdenberg, AMjm, Palotie, A, Zwart, J-A
Corporate AuthorsInternational Headache Genetics Consortium
Date Published2018 02
KeywordsAdolescent, Adult, Case-Control Studies, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Genome-Wide Association Study, Headache Disorders, Humans, Retrospective Studies, Young Adult

Background The biological mechanisms of headache chronification are poorly understood. We aimed to identify changes in DNA methylation associated with the transformation from episodic to chronic headache. Methods Participants were recruited from the population-based Norwegian HUNT Study. Thirty-six female headache patients who transformed from episodic to chronic headache between baseline and follow-up 11 years later were matched against 35 controls with episodic headache. DNA methylation was quantified at 485,000 CpG sites, and changes in methylation level at these sites were compared between cases and controls by linear regression analysis. Data were analyzed in two stages (Stages 1 and 2) and in a combined meta-analysis. Results None of the top 20 CpG sites identified in Stage 1 replicated in Stage 2 after multiple testing correction. In the combined meta-analysis the strongest associated CpG sites were related to SH2D5 and NPTX2, two brain-expressed genes involved in the regulation of synaptic plasticity. Functional enrichment analysis pointed to processes including calcium ion binding and estrogen receptor pathways. Conclusion In this first genome-wide study of DNA methylation in headache chronification several potentially implicated loci and processes were identified. The study exemplifies the use of prospectively collected population cohorts to search for epigenetic mechanisms of disease.


Alternate JournalCephalalgia
PubMed ID28103696