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Author (up) Winsvold, B.S.; Palta, P.; Eising, E.; Page, C.M.; van den Maagdenberg, A.M.; Palotie, A.; Zwart, J.-A. url  doi
  Title Epigenetic DNA methylation changes associated with headache chronification: A retrospective case-control study Type Journal Article
  Year 2018 Publication Cephalalgia : an International Journal of Headache Abbreviated Journal Cephalalgia  
  Volume 38 Issue 2 Pages 312-322  
  Keywords Adolescent; Adult; Case-Control Studies; CpG Islands/genetics; DNA Methylation/*genetics; Epigenesis, Genetic; Female; Genome-Wide Association Study; Headache Disorders/*genetics; Humans; Retrospective Studies; Young Adult; *Chronic headache; *cohort studies; *epigenetics  
  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.  
  Address 2 Institute of Clinical Medicine, University of Oslo, Oslo, Norway  
  Corporate Author International Headache Genetics Consortium Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0333-1024 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28103696 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2189  
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