title: Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions.
abstract: OBJECTIVE
  As the primary relevant tissue (brain) for psychiatric disorders is commonly not available, we aimed to investigate whether blood can be used as a proxy in methylation studies on the basis of two models. In the 'signature' model methylation-disease associations occur because a disease-causing factor affected methylation in the blood. In the 'mirror-site' model the methylation status in the blood is correlated with the corresponding disease-causing site in the brain. MATERIALS, METHODS & RESULTS: Methyl-binding domain enrichment and next-generation sequencing of the blood, cortex and hippocampus from four haloperidol-treated and ten untreated C57BL/6 mice revealed high levels of correlation in methylation across tissues. Despite the treatment inducing a large number of methylation changes, this correlation remains high.
  
  
  CONCLUSIONS
  Our results show that, consistent with the signature model, factors that affect brain processes (i.e., haloperidol) leave biomarker signatures in the blood and, consistent with the mirror-site model, the methylation status of many sites in the blood mirror those in the brain.
authors.affiliation: Center for Biomarker Research & Personalized Medicine, School of Pharmacy, Virginia Commonwealth University, 1112 East Clay Street, PO Box 980533, Richmond, VA 23298, USA. kaaberg@vcu.edu
authors.forename: Karolina A
authors.initials: KA
authors.lastname: Aberg
authors.forename: Lin Y
authors.initials: LY
authors.lastname: Xie
authors.forename: Joseph L
authors.initials: JL
authors.lastname: McClay
authors.forename: Srilaxmi
authors.initials: S
authors.lastname: Nerella
authors.forename: Sarah
authors.initials: S
authors.lastname: Vunck
authors.forename: Sarah
authors.initials: S
authors.lastname: Snider
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Beardsley
authors.forename: Edwin J C G
authors.initials: EJ
authors.lastname: van den Oord
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000097:blood* / Q000235:genetics; D044127:Epigenesis, Genetic; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D001523:Mental Disorders / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D004268:DNA-Binding Proteins; D006220:Haloperidol
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