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Cephalalgia. 2018 Feb;38(2):312-322. doi: 10.1177/0333102417690111. Epub 2017 Jan 19.

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

Author information

1
1 FORMI and Department of Neurology, Oslo University Hospital, Oslo, Norway.
2
2 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
3
3 Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
4
4 Estonian Genome Center, University of Tartu, Tartu, Estonia.
5
5 Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
6
6 Norwegian Institute of Public Health, Oslo, Norway.
7
7 Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
8
8 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
9
9 Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, USA.
10
10 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA.
11
11 Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
12
12 Department of Neurology, Massachusetts General Hospital, Boston, USA.

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.

KEYWORDS:

Chronic headache; cohort studies; epigenetics

PMID:
28103696
DOI:
10.1177/0333102417690111

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