Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for .

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,  = 45) and candidate gene methylation using EpiTYPER ( = 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 () revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson  = 0.517,  = 0.002; average methylation Pearson  = 0.332,  = 0.039). Cord blood 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 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for methylation in association with stress and provide grounds for further research.