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

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http://hdl.handle.net/10138/300966

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Int Headache Genetics Consortium 2018 , ' Epigenetic DNA methylation changes associated with headache chronification : A retrospective case-control study ' , Cephalalgia , vol. 38 , no. 2 , pp. 312-322 . https://doi.org/10.1177/0333102417690111

Title: Epigenetic DNA methylation changes associated with headache chronification : A retrospective case-control study
Author: Int Headache Genetics Consortium
Date: 2018-02
Language: eng
Number of pages: 11
Belongs to series: Cephalalgia
ISSN: 0333-1024
URI: http://hdl.handle.net/10138/300966
Abstract: 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.
Subject: Chronic headache
cohort studies
epigenetics
NORD-TRONDELAG HEALTH
CHRONIC MIGRAINE
CELL-ADHESION
HUNT
VALIDITY
BRAIN
QUESTIONNAIRE
INTERNEURONS
OVERUSE
3112 Neurosciences
3124 Neurology and psychiatry
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