DNA methylation patterns in T lymphocytes are generally stable in human pregnancies but CD3 methylation is associated with perinatal psychiatric symptoms

OBJECTIVES: To determine whether DNA methylation patterns in genes coding for selected T-lymphocyte proteins are associated with perinatal psychiatric distress or with complications of pregnancy. METHODS: T lymphocyte DNA was obtained from pregnant women across three time points in pregnancy and the postpartum period and epigenetic patterns were assessed using Illumina 450 ​K Methylation Beadchips. Seven selected genes critical for T cell function were analyzed for methylation changes during pregnancy and for associations of methylation patterns with psychiatric distress or with pregnancy complications, with particular attention paid to spatial aggregations of methyl groups, termed ‘hotspots,’ within the selected genes. RESULTS: In the candidate gene approach, DNA methylation density within a single cluster of 9 contiguous CpG loci within the CD3 gene was found to be strongly associated with anxiety and depression in mid- and late pregnancy, and weakly associated with the presence of complications of pregnancy. Average DNA methylation density across each of the seven genes examined, and assay-wide, was found to be relatively stable across pregnancy and postpartum, but methylation within the CD3 hotspot was more malleable and changes over time were coordinated across the nine cytosines in the hotspot. CD3 CpGs did not pass array-wide tests for significance, but CpG clusters in two other genes, DTNBP1 and OXSR1, showed array-wide significant associations with anxiety. CONCLUSIONS: Despite the need for tolerating the fetal hemi-allograft, overall DNA methylation patterns in T lymphocytes are generally stable over the mid to late course of human pregnancies and postpartum. However, site-specific changes in DNA methylation density in CD3 appear linked to both symptoms of depression and anxiety in pregnancy and, less strongly, to adverse pregnancy outcomes.