Stress and DNA Methylation of Blood Leukocytes among Pregnant Latina Women

Abstract

Latinas experience physical and psychological stressors in pregnancy leading to increased morbidity and higher risk for adverse birth outcomes. Epigenetic changes, including DNA methylation (DNAm), have been proposed as markers to create more refined risk stratification, yet few of these studies have examined these changes in Latinas. We conducted a secondary analysis of stored blood leukocytes of Latina women (n = 58) enrolled in a larger National Institutes of Health funded R01 project (2011-2016). We examined DNAm on eight candidate stress genes to compare physically and psychologically stressed participants to healthy (low stress) participants. We found unique CpGs that were differentially methylated in stressed women early- and mid-pregnancy compared to the healthy group, though none remained significant after FDR correction. Both physical and psychological stress were associated with hypomethylation at two consecutive CpG sites on NR3C1 in early pregnancy and one CpG site on NR3C1 in mid-pregnancy before adjustment. Stress was also associated with hypomethylation at two CpG sites on FKBP5 in early and mid-pregnancy but were no longer significant after FDR adjustment. Though we did not find statistically significant differences in DNAm during pregnancy between stressed and healthy women in this sample, signals were consistent with previous findings. Future work in larger samples should further examine the associations between stress and DNAm in pregnancy as this mechanism may explain underlying perinatal health inequities.

Keywords: Hispanic; Latino; epigenetics; pregnancy; stress.

Figure 1

Flow chart of participant inclusion in the present study.

Figure 2

Venn diagram of the number of differentially methylated CpG sites before FDR adjustment in Physically and Psychologically stressed women relative to healthy women at T1 (A) and T2 (B).

Figure 3

CpG sites for candidate genes for each stress group by genomic position and time point. Significantly differentiated methylated sites (p-value < 0.05) are represented by their t-value with red indicating hypermethylation (darker red indicating more hypermethylated) and blue hypomethylation (darker blue indicating more hypomethylated) in stress groups relative to the healthy group.

Figure 4

Representative regional plots illustrating part of NR3C1 gene and investigated CpGs, highlighting the differentially methylated sites in psychologically (A) and physically (B) stressed women relative to healthy women, respectively, at Time 1. The upper panels present the log transformed p-values with red dotted line as the cutoff used (p ≤ 0.05). Below is the ENSEMBL track annotation and the correlation of methylation levels among all CpGs in this selected region.