TY  - JOUR
A1  - Vangeel, Elise Beau
A1  - Pishva, Ehsan
A1  - Hompes, Titia
A1  - van den Hove, Daniel
A1  - Lambrechts, Diether
A1  - Allegaert, Karel
A1  - Freson, Kathleen
A1  - Izzi, Benedetta
A1  - Claes, Stephan
T1  - Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for \(GABBR1\)
JF  - Clinical Epigenetics
N2  - Background: There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach.
Methods: We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity.
Results: Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old.
Conclusions: In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.
KW  - DNA methylation
KW  - GABBR1
KW  - gender differences
KW  - HPA axis
KW  - pregnancy anxiety
KW  - prenatal stress
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173825
VL  - 9
ER  - 
TY  - JOUR
A1  - Pishva, Ehsan
A1  - Drukker, Marjan
A1  - Viechtbauer, Wolfgang
A1  - Decoster, Jeroen
A1  - Collip, Dina
A1  - van Winkel, Ruud
A1  - Wichers, Marieke
A1  - Jacobs, Nele
A1  - Thiery, Evert
A1  - Derom, Catherine
A1  - Geschwind, Nicole
A1  - van den Hove, Daniel
A1  - Lataster, Tineke
A1  - Myin-Germeys, Inez
A1  - van Os, Jim
A1  - Rutten, Bart P. F.
A1  - Kenis, Gunter
T1  - Epigenetic Genes and Emotional Reactivity to Daily Life Events: A Multi-Step Gene-Environment Interaction Study
JF  - PLOS ONE
N2  - 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.
KW  - DNA methylation
KW  - de-novo methylation
KW  - psychotic experiences
KW  - DNMT3A
KW  - glucocorticoid receptor
KW  - stress
KW  - mammalian development
KW  - psychiatry
KW  - cortisol
KW  - cells
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115956
SN  - 1932-6203
VL  - 9
IS  - 6
ER  -