DNA modification study of major depressive disorder: beyond locus-by-locus comparisons

Oh, Gabriel, Wang, Sun-Chong, Pal, Mrinal, Chen, Zheng Fei, Khare, Tarang, Tochigi, Mamoru, Ng, Catherine, Yang, Yeqing A., Kwan, Andrew, Kaminsky, Zachary A., Mill, Jonathan, Gunasinghe, Cerisse, Tackett, Jennifer L., Gottesman, Irving I., Willemsen, Gonneke, de Geus, Eco J. C., Vink, Jacqueline M., Slagboom, P. Eline, Wray, Naomi R., Heath, Andrew C., Montgomery, Grant W., Turecki, Gustavo, Martin, Nicholas G., Boomsma, Dorret I., McGuffin, Peter, Kustra, Rafal and Petronis, Art (2014) DNA modification study of major depressive disorder: beyond locus-by-locus comparisons. Biological Psychiatry, 77 3: 246-255. doi:10.1016/j.biopsych.2014.06.016


Author Oh, Gabriel
Wang, Sun-Chong
Pal, Mrinal
Chen, Zheng Fei
Khare, Tarang
Tochigi, Mamoru
Ng, Catherine
Yang, Yeqing A.
Kwan, Andrew
Kaminsky, Zachary A.
Mill, Jonathan
Gunasinghe, Cerisse
Tackett, Jennifer L.
Gottesman, Irving I.
Willemsen, Gonneke
de Geus, Eco J. C.
Vink, Jacqueline M.
Slagboom, P. Eline
Wray, Naomi R.
Heath, Andrew C.
Montgomery, Grant W.
Turecki, Gustavo
Martin, Nicholas G.
Boomsma, Dorret I.
McGuffin, Peter
Kustra, Rafal
Petronis, Art
Title DNA modification study of major depressive disorder: beyond locus-by-locus comparisons
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
1873-2402
Publication date 2014-01-02
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2014.06.016
Open Access Status DOI
Volume 77
Issue 3
Start page 246
End page 255
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2015
Language eng
Formatted abstract
Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined.

Methods: We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies.

Results: In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD.

Conclusions: Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations.
Keyword DNA modification
Epigenetic outliers
Epigenetics
Heteroscedasticity
Major depressive disorder
Molecular networks
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 1 July 2014.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Medicine Publications
 
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