Association between Maternal Depression during Pregnancy and Newborn DNA Methylation

Abstract Around 15% to 65% of women globally experience depression during pregnancy, prevalence being particularly high in low- and middle-income countries. Prenatal depression has been associated with adverse birth and child development outcomes. DNA methylation (DNAm) may aid in understanding this association. In this project, we analyzed associations between prenatal depression and DNAm from cord blood from participants of the South African Drakenstein Child Health Study. We examined DNAm in an epigenome wide association study (EWAS) of 248 mother child pairs. DNAm was measured using the Infinium MethylationEPIC (N=145) and the Infinium HumanMethylation450 (N=103) arrays. Prenatal depression scores, obtained with the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Depression Inventory II (BDI-II), were analyzed as continuous and dichotomized variables. We used linear robust models to estimate associations between depression and newborn DNAm, adjusted for measured (smoking status, household income, sex, preterm birth, cell type proportions, and genetic principal components) and unmeasured confounding using Cate and Bacon algorithms. Bonferroni correction was used to adjust for multiple testing. DMRcate was used to test for differentially methylated regions (DMRs). Differential DNAm in GNAS (cg22798925, Δ beta per IQR(EPDS)=0.0066, p= 1.06 × 10 −7 ) was significantly associated with EPDS. For dichotomized BDI-II thresholds, Differential DNAm in CTNNA2 (cg04859497, Δ beta=-0.064, p= 8.09 × 10 −10 ) and OSBPL10 (cg27278221, Δ beta=-0.020, p= 5.40 × 10 −8 ) was significantly associated with the dichotomized BDI-II variables. Eight DMRs were associated with at least two depression scales. Further studies are needed to replicate these findings and investigate their biological impact.