Genome-wide DNA methylation scan in major depressive disorder
| Autor: | 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., Consortium, GenRED, Holmans, Peter Alan |
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| Rok vydání: | 2011 |
| Předmět: |
Epidemiology
lcsh:Medicine Biochemistry Epigenesis Genetic 0302 clinical medicine Molecular cell biology lcsh:Science Genetics Psychiatry 0303 health sciences Molecular Epidemiology Multidisciplinary Brain Methylation Genomics Genome Scans Nucleic acids Mental Health CpG site Genetic Epidemiology DNA methylation Major depressive disorder Medicine Epigenetics DNA modification Research Article Biophysics Nerve Tissue Proteins Neuropsychiatric Disorders Biology 03 medical and health sciences Genome Analysis Tools medicine Humans Gene Genetic Association Studies 030304 developmental biology Depressive Disorder Major Mood Disorders lcsh:R dNaM Membrane Proteins DNA DNA Methylation medicine.disease PRIMA1 R1 lcsh:Q CpG Islands Gene expression 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 4, p e34451 (2012) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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