Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions. (August 2013)

• Record Type: Journal Article
• Authors: Aberg, Karolina A; Xie, Lin Y; McClay, Joseph L; Nerella, Srilaxmi; Vunck, Sarah; Snider, Sarah; Beardsley, Patrick M; van den Oord, Edwin JCG
• Is Part Of: Epigenomics. Volume 5:Number 4(2013)
• Page Start: 367
• Page End: 377
• Publication Date: 2013-08
• Subjects: antipsychotic -- DNA methylation -- methyl-CpG binding domain -- methylome-wide association study -- mirror-site model -- next-generation sequencing -- signature model; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi.13.36
• Languages: English
• ISSNs: 1750-1911

Abstract

Aim: 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.Conclusion: 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.