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Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

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Matthew N Davies, Lutz Krause, Jordana T Bell, Fei Gao, Kirsten J Ward, Honglong Wu, Hanlin Lu, Yuan Liu, Pei-Chein Tsai, David A Collier, Therese Murphy, Emma Dempster, Jonathan Mill, Alexis Battle, Sara Mostafavi, Xiaowei Zhu, Anjali Henders, Enda Byrne, Naomi R Wray, Nicholas G Martin & 3 more Tim D Spector, Jun Wang, UK Brain Expression Consortium

Original languageEnglish
Article numberR56
Number of pages12
JournalGENOME BIOLOGY
Volume15
Issue number4
DOIs
Published2014

King's Authors

Abstract

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.

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