Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

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; Tim D Spector; Jun Wang; UK Brain Expression Consortium

doi:10.1186/gb-2014-15-4-r56

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

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 MartinTim D Spector, Jun Wang, UK Brain Expression Consortium

Research output: Contribution to journal › Article › peer-review

84 Citations (Scopus)

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.

Original language	English
Article number	R56
Number of pages	12
Journal	GENOME BIOLOGY
Volume	15
Issue number	4
DOIs	https://doi.org/10.1186/gb-2014-15-4-r56
Publication status	Published - 2014

Keywords

Adult
Aged
Case-Control Studies
DNA Methylation
Depressive Disorder, Major
Female
Gene Regulatory Networks
Humans
Male
Middle Aged
Nerve Tissue Proteins
Transcription Factors
Twins, Monozygotic

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Davies, M. N., Krause, L., Bell, J. T., Gao, F., Ward, K. J., Wu, H., Lu, H., Liu, Y., Tsai, P.-C., Collier, D. A., Murphy, T., Dempster, E., Mill, J., Battle, A., Mostafavi, S., Zhu, X., Henders, A., Byrne, E., Wray, N. R., ... UK Brain Expression Consortium (2014). Hypermethylation in the ZBTB20 gene is associated with major depressive disorder. GENOME BIOLOGY, 15(4), Article R56. https://doi.org/10.1186/gb-2014-15-4-r56

@article{83062d62063643faaf03c66a1020b72e,

title = "Hypermethylation in the ZBTB20 gene is associated with major depressive disorder",

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.",

keywords = "Adult, Aged, Case-Control Studies, DNA Methylation, Depressive Disorder, Major, Female, Gene Regulatory Networks, Humans, Male, Middle Aged, Nerve Tissue Proteins, Transcription Factors, Twins, Monozygotic",

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

year = "2014",

doi = "10.1186/gb-2014-15-4-r56",

language = "English",

volume = "15",

journal = "GENOME BIOLOGY",

issn = "1465-6906",

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number = "4",

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Davies, MN, Krause, L, Bell, JT, Gao, F, Ward, KJ, Wu, H, Lu, H, Liu, Y, Tsai, P-C , Collier, DA, Murphy, T, Dempster, E, Mill, J, Battle, A, Mostafavi, S, Zhu, X, Henders, A, Byrne, E, Wray, NR, Martin, NG, Spector, TD, Wang, J & UK Brain Expression Consortium 2014, 'Hypermethylation in the ZBTB20 gene is associated with major depressive disorder', GENOME BIOLOGY, vol. 15, no. 4, R56. https://doi.org/10.1186/gb-2014-15-4-r56

TY - JOUR

T1 - Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

AU - Davies, Matthew N

AU - Krause, Lutz

AU - Bell, Jordana T

AU - Gao, Fei

AU - Ward, Kirsten J

AU - Wu, Honglong

AU - Lu, Hanlin

AU - Liu, Yuan

AU - Tsai, Pei-Chein

AU - Collier, David A

AU - Murphy, Therese

AU - Dempster, Emma

AU - Mill, Jonathan

AU - Battle, Alexis

AU - Mostafavi, Sara

AU - Zhu, Xiaowei

AU - Henders, Anjali

AU - Byrne, Enda

AU - Wray, Naomi R

AU - Martin, Nicholas G

AU - Spector, Tim D

AU - Wang, Jun

AU - UK Brain Expression Consortium

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Case-Control Studies

KW - DNA Methylation

KW - Depressive Disorder, Major

KW - Female

KW - Gene Regulatory Networks

KW - Humans

KW - Male

KW - Middle Aged

KW - Nerve Tissue Proteins

KW - Transcription Factors

KW - Twins, Monozygotic

U2 - 10.1186/gb-2014-15-4-r56

DO - 10.1186/gb-2014-15-4-r56

M3 - Article

C2 - 24694013

SN - 1465-6906

VL - 15

JO - GENOME BIOLOGY

JF - GENOME BIOLOGY

IS - 4

M1 - R56

ER -

Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

Abstract

Keywords

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