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.

DNMT3A Moderates Cognitive Decline in Subjects with Mild Cognitive Impairment: Replicated Evidence from Two Mild Cognitive Impairment Cohorts

“…More specifically, MCI subjects carrying the TT genotype at rs11887120 in DNMT3A in both cohorts showed greater cognitive decline over time than CC carriers. In addition, we observed statistically significant associations between SNP rs1265764 in DNMT3A and change in cognitive decline over time in both cohorts, albeit that the direction of effect was opposite to each other in the two samples, which may be related to 'flip-flop' patterns of genetic association [12].…”

Epigenetic dysfunctional diseases and therapy for infection and inflammation

“…Epigenetic states are also modified by the emotional health of an individual as studies were done with psychosis, psychotic disorders, and severe depression [101]. Anti-androgenic compound ‘vinclozolin’, an anti-fungal agent used in vineyards or chemical methoxychlor, an oestrogenic compound used as a pesticide, can cause reproductive abnormalities in laboratory animals.…”

Epigenetics and Child Psychiatry: Ethical and Legal Issues

“…Epigenetics seeks to elucidate these interactions affecting gene expression, such as the influence of child maltreatment on those with genetic vulnerability (Yang et al, ). Recent research has shown how daily events can have an impact on the epigenetic regulatory genes and that emotional responses may be moderated by the genetic variations in the genes that control epigenetic processes (Pishva et al, ). Studies also indicate that epigenetic mechanisms are especially vulnerable to disruption during critical phases of development, including gestation, infancy, puberty, and old age (Feinberg, ; Kerverne, ).…”