Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities
Open Access
- 1 August 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in International Journal of Neuropsychopharmacology
- Vol. 16 (7), 1513-1528
- https://doi.org/10.1017/s1461145713000102
Abstract
Monoamine oxidase A (MAOA) harbours a polymorphic upstream variable-number tandem repeat (u-VNTR). The MAOA-L allele of the u-VNTR leads to decreased gene expression levels in vitro and has been found to increase the risk of conduct disorder in males with childhood adversities. Early-life adversities have been associated with hypermethylation of the glucocorticoid receptor (NR3C1). In this study, we first performed a genetic association analysis of the MAOA u-VNTR using individuals with depression (n = 392) and controls (n = 1276). Next, DNA methylation analyses of MAOA and NR3C1 were performed using saliva samples of depressed and control subgroups. Adult MAOA-L females with childhood adversities were found to have a higher risk of developing depression (p = 0.006) and overall MAOA methylation levels were decreased in depressed females compared to controls (mean depressed, 42% vs. mean controls, 44%; p = 0.04). One specific childhood adversity [early parental death (EPD)] was associated with hypermethylation of NR3C1 close to an NGFI-A binding site (mean EPD, 19% vs. mean non-EPD, 14%; p = 0.005). Regression analysis indicated that this association may be mediated by the MAOA-L allele (adjusted R2 = 0.24, ANOVA: F = 23.48, p < 0.001). Conclusively: (1) depression in females may result from a gene × childhood-adversity interaction and/or a dysregulated epigenetic programming of MAOA; (2) childhood-adversity subtypes may differentially impact DNA methylation at NR3C1; (3) baseline MAOA-genotypic variations may affect the extent of NR3C1 methylation.Keywords
This publication has 75 references indexed in Scilit:
- Monoamine oxidase A gene DNA hypomethylation – a risk factor for panic disorder?International Journal of Neuropsychopharmacology, 2012
- Conceptual and Methodological Issues in Neuroimaging Studies of the Effects of Child MaltreatmentArchives of Pediatrics & Adolescent Medicine, 2011
- Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-CarboxylcytosineScience, 2011
- Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult BrainCell, 2011
- Socioeconomic status and the brain: mechanistic insights from human and animal researchNature Reviews Neuroscience, 2010
- Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1Science, 2009
- Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuseNature Neuroscience, 2009
- Associations of a Regulatory Polymorphism of Monoamine Oxidase-A Gene Promoter (MAOA-uVNTR) With Symptoms of Depression and Sleep QualityPsychosomatic Medicine, 2007
- The Major Depression Inventory versus Schedules for Clinical Assessment in Neuropsychiatry in a population sampleSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 2005
- Epigenetic programming by maternal behaviorNature Neuroscience, 2004