title: Epigenetic genes and emotional reactivity to daily life events: a multi-step gene-environment interaction study.
abstract: Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery.
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Ehsan
authors: E
authors: Pishva
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Marjan
authors: M
authors: Drukker
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Wolfgang
authors: W
authors: Viechtbauer
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Jeroen
authors: J
authors: Decoster
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Dina
authors: D
authors: Collip
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Ruud
authors: R
authors: van Winkel
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Marieke
authors: M
authors: Wichers
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands; School of Psychology, Open University of the Netherlands, Heerlen, The Netherlands.
authors: Nele
authors: N
authors: Jacobs
authors: Department of Neurology, Ghent University Hospital, Ghent, Belgium.
authors: Evert
authors: E
authors: Thiery
authors: Centre of Human Genetics, University Hospital Leuven, and Department of Human Genetics, KU Leuven, Leuven, Belgium.
authors: Catherine
authors: C
authors: Derom
authors: Department of Clinical Psychological Science, Maastricht University, Maastricht, The Netherlands.
authors: Nicole
authors: N
authors: Geschwind
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Psychiatry, and Molecular Psychiatry, Laboratory of Translational Neuroscience, University of Würzburg, Würzburg, Germany.
authors: Daniel
authors: D
authors: van den Hove
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Tineke
authors: T
authors: Lataster
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Inez
authors: I
authors: Myin-Germeys
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, London, United Kingdom.
authors: Jim
authors: J
authors: van Os
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Bart P F
authors: BP
authors: Rutten
authors: School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Gunter
authors: G
authors: Kenis
mesh_terms: D000328:Adult; D004644:Emotions; D044127:Epigenesis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008875:Middle Aged; D057181:Pleasure; D020641:Polymorphism, Single Nucleotide; D013315:Stress, Psychological; D055815:Young Adult