Study Report

CitationDavies MN, 2014 PubMed
Full InfoDavies MN, Krause L, Bell JT, Gao F, Ward KJ, Wu H, Lu H, et al. (2014) Hypermethylation in the ZBTB20 gene is associated with major depressive disorder.Genome Biology 2014, 15:R56 doi:10.1186/gb-2014-15-4-r56

Hypothesis or Background Although genetic variation is believed to contribute to an individual¡¯s susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder.
Sample Informationa total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression; an independent cohort of 356 unrelated case-control individuals.
Method Detail"In this study we used methylated DNA immunoprecipitation combined with ultra-deep sequencing (MeDIP-seq) to provide comprehensive coverage of the methylomic landscape in order to compare blood samples between MZT pairs discordant for MDD in two independent datasets;The overall design was a meta-analysis of whole blood genome-wide methylation in two cohorts of MZT pairs discordant for MDD, followed by replication in an independent case-control group and exploration of expression and methylation signals in independent brain tissue samples."
Method Keywordsultra-deep sequencing (MeDIP-seq);methylated DNA immunoprecipitation;meta-analysis
Result"Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder."
ConclusionsOur results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease.

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