Hypermethylation in the ZBTB20 gene is associated with major depressive disorder.
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.
Matthew N
MN
Davies
Lutz
L
Krause
Jordana T
JT
Bell
Fei
F
Gao
Kirsten J
KJ
Ward
Honglong
H
Wu
Hanlin
H
Lu
Yuan
Y
Liu
Pei-Chein
PC
Tsai
David A
DA
Collier
Therese
T
Murphy
Emma
E
Dempster
Jonathan
J
Mill
Alexis
A
Battle
Sara
S
Mostafavi
Xiaowei
X
Zhu
Anjali
A
Henders
Enda
E
Byrne
Naomi R
NR
Wray
Nicholas G
NG
Martin
Tim D
TD
Spector
Jun
J
Wang
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics
D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C427486:ZBTB20 protein, human