Hypermethylation in the ZBTB20 gene is associated with major depressive disorder.
UK Brain Expression Consortium
© 2014 Davies et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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. RESULTS: 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. CONCLUSIONS: Our 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.
The study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) Clinical Research Facility at Guy’s & St Thomas’ Davies et al. Genome Biology 2014, 15:R56 Page 9 of 12 http://genomebiology.com/2014/15/4/R56 NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. Matthew Davies is supported by the EU FP7 grant EuroBATS (No. 259749). Tim Spector is an NIHR senior Investigator and is holder of an ERC Advanced Principal Investigator award. Further funding support for this project was obtained from the European Research Council (project number 250157). The members of the UK Brain Expression Consortium (UKBEC) are: (1) Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK: John A Hardy, Mina Ryten, and Daniah Trabzuni; (2) Department of Medical and Molecular Genetics, King's College London, UK: Michael E Weale, Adaikalavan Ramasamy and Paola Forabosco; (3) Department of Pathology, The University of Edinburgh, Wilkie Building, Teviot Place, Edinburgh, UK: Colin Smith and Robert Walker. Australia: funding for phenotype and blood collection was from NHMRC grants to Nick Martin and NIH grants to Andrew Heath and Pamela Madden. We thank David Smyth for database management, Lisa Bowdler for sample preparation, and the twins for their cooperation.
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Vol. 15: R56
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