Genome-wide DNA methylation scan in major depressive disorder.

Sarven Sabunciyan, Martin J. Aryee, Rafael A. Irizarry, Michael Rongione, Maree J. Webster, Walter E. Kaufman, Peter Murakami, Andree Lessard, Robert H. Yolken, Andrew P. Feinberg, James B. Potash, Consortium GenRED Consortium

Research output: Contribution to journalArticle

Abstract

While genome-wide association studies are ongoing to identify sequence variation influencing susceptibility to major depressive disorder (MDD), epigenetic marks, such as DNA methylation, which can be influenced by environment, might also play a role. Here we present the first genome-wide DNA methylation (DNAm) scan in MDD. We compared 39 postmortem frontal cortex MDD samples to 26 controls. DNA was hybridized to our Comprehensive High-throughput Arrays for Relative Methylation (CHARM) platform, covering 3.5 million CpGs. CHARM identified 224 candidate regions with DNAm differences >10%. These regions are highly enriched for neuronal growth and development genes. Ten of 17 regions for which validation was attempted showed true DNAm differences; the greatest were in PRIMA1, with 12-15% increased DNAm in MDD (p = 0.0002-0.0003), and a concomitant decrease in gene expression. These results must be considered pilot data, however, as we could only test replication in a small number of additional brain samples (n = 16), which showed no significant difference in PRIMA1. Because PRIMA1 anchors acetylcholinesterase in neuronal membranes, decreased expression could result in decreased enzyme function and increased cholinergic transmission, consistent with a role in MDD. We observed decreased immunoreactivity for acetylcholinesterase in MDD brain with increased PRIMA1 DNAm, non-significant at p = 0.08.While we cannot draw firm conclusions about PRIMA1 DNAm in MDD, the involvement of neuronal development genes across the set showing differential methylation suggests a role for epigenetics in the illness. Further studies using limbic system brain regions might shed additional light on this role.

Original languageEnglish (US)
Article numbere34451
JournalPLoS One
Volume7
Issue number4
StatePublished - 2012

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Major Depressive Disorder
DNA methylation
DNA Methylation
Genes
Genome
genome
Methylation
methylation
Brain
Acetylcholinesterase
acetylcholinesterase
brain
Epigenomics
epigenetics
Throughput
Limbic System
Genome-Wide Association Study
cholinergic agents
Frontal Lobe
Anchors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sabunciyan, S., Aryee, M. J., Irizarry, R. A., Rongione, M., Webster, M. J., Kaufman, W. E., ... GenRED Consortium, C. (2012). Genome-wide DNA methylation scan in major depressive disorder. PLoS One, 7(4), [e34451].

Genome-wide DNA methylation scan in major depressive disorder. / Sabunciyan, Sarven; Aryee, Martin J.; Irizarry, Rafael A.; Rongione, Michael; Webster, Maree J.; Kaufman, Walter E.; Murakami, Peter; Lessard, Andree; Yolken, Robert H.; Feinberg, Andrew P.; Potash, James B.; GenRED Consortium, Consortium.

In: PLoS One, Vol. 7, No. 4, e34451, 2012.

Research output: Contribution to journalArticle

Sabunciyan, S, Aryee, MJ, Irizarry, RA, Rongione, M, Webster, MJ, Kaufman, WE, Murakami, P, Lessard, A, Yolken, RH, Feinberg, AP, Potash, JB & GenRED Consortium, C 2012, 'Genome-wide DNA methylation scan in major depressive disorder.', PLoS One, vol. 7, no. 4, e34451.
Sabunciyan S, Aryee MJ, Irizarry RA, Rongione M, Webster MJ, Kaufman WE et al. Genome-wide DNA methylation scan in major depressive disorder. PLoS One. 2012;7(4). e34451.
Sabunciyan, Sarven ; Aryee, Martin J. ; Irizarry, Rafael A. ; Rongione, Michael ; Webster, Maree J. ; Kaufman, Walter E. ; Murakami, Peter ; Lessard, Andree ; Yolken, Robert H. ; Feinberg, Andrew P. ; Potash, James B. ; GenRED Consortium, Consortium. / Genome-wide DNA methylation scan in major depressive disorder. In: PLoS One. 2012 ; Vol. 7, No. 4.
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