Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

Davies, Matthew N., Krause, Lutz, Bell, Jordana T., Gao, Fei, Ward, Kirsten J., Wu, Honglong, Lu, Hanlin, Liu, Yuan, Tsai, Pei-Chein, Collier, David A., Murphy, Therese, Dempster, Emma, Mill, Jonathan, UK Brain Expression Consortium, Battle, Alexis, Mostafavi, Sara, Zhu, Xiaowei, Henders, Anjali, Byrne, Enda, Wray, Naomi R., Martin, Nicholas G., Spector, Tim D. and Wang, Jun (2014) Hypermethylation in the ZBTB20 gene is associated with major depressive disorder. Genome Biology, 15 4: R56.1-R56.12. doi:10.1186/gb-2014-15-4-r56


Author Davies, Matthew N.
Krause, Lutz
Bell, Jordana T.
Gao, Fei
Ward, Kirsten J.
Wu, Honglong
Lu, Hanlin
Liu, Yuan
Tsai, Pei-Chein
Collier, David A.
Murphy, Therese
Dempster, Emma
Mill, Jonathan
UK Brain Expression Consortium
Battle, Alexis
Mostafavi, Sara
Zhu, Xiaowei
Henders, Anjali
Byrne, Enda
Wray, Naomi R.
Martin, Nicholas G.
Spector, Tim D.
Wang, Jun
Title Hypermethylation in the ZBTB20 gene is associated with major depressive disorder
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-760X
Publication date 2014-04-02
Year available 2014
Sub-type Article (original research)
DOI 10.1186/gb-2014-15-4-r56
Open Access Status DOI
Volume 15
Issue 4
Start page R56.1
End page R56.12
Total pages 12
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 1105 Ecology, Evolution, Behavior and Systematics
1311 Genetics
1307 Cell Biology
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.
Formatted 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.
Keyword Genome-Wide Association
DNA-Methylation
Hippocampal Volume
Metaanalysis
Expression
Stress
Sample
Twins
Risk
Differentiation
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 259749
250157
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
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