Parenting Stress and DNA Methylation Among African-Americans in the Intergen Study

Purpose: The experiences of parenting can cause stress related to work, life events, environment, marital relationship, daily hassles, and child rearing responsibilities. African American (AA) mothers have higher levels of parenting stress than mothers of European Ancestry (EA), which can contribute to adverse health outcomes in both child and mother. Parenting stress among AA populations has been correlated with risk factors associated with health disparities in AA populations. This suggests parenting stress may contribute to overall maternal stress, influencing health outcomes of the mother and child similar to other forms of psychological stress. For example, in a previous study we observed higher diastolic blood pressure in AA caregivers reporting higher levels of parenting stress (Jacquelyn Y Taylor, Washington, Artinian, & Lichtenberg, 2007). Chemical modifications to the genome that do not alter the nucleotide sequence may alter gene expression are referred to as epigenetic changes, and recent evidence has implicated epigenetic alterations, such as changes in DNA methylation (DNAm), in the pathogenesis of complex disease states (Wright, Ralph, Ohm, & Anderson, 2013). General life stress and financial stress, have been associated with altered DNAm in AA populations (Chen, Miller, Yu, & Brody, 2016), although the relationship between parenting stress and DNAm have not yet been described. The purpose of this study was to examine the relationship between maternal parenting stress and DNAm among African American mothers and their children.

Methods: This study evaluated epigenome-wide DNAm in 74 mother-child dyads involved in our current prospective study examining the intergenerational impact of genetic and psychological factors on blood pressure. Extensive details on recruitment and statistical methods have been described elsewhere (Crusto, Barcelona de Mendoza, Connell, Sun, & Taylor, 2016; J. Y. Taylor, Wright, Crusto, & Sun, 2016). Briefly, AA mothers were recruited from the community who had a child between the ages of 3-5 years of age. Baseline demographic data and the Parenting Stress Index – Short Form (PSI) (Abidin, 1995) was obtained via audio self-assisted interviewing software. Saliva samples were collected from mothers and children for DNAm analyses with the Illumina Infinium Methylation EPIC (850K) BeadChip. PSI scores were calculated per instructions in the protocol manual (Abidin, 1995). DNAm data were assessed for quality and preprocessing using an established analytic pipeline for DNAm array data (J. Y. Taylor et al., 2016). Descriptive statistics were completed to describe the sample and linear mixed models were used to evaluate DNAm (depended variable) in mothers and children related to maternal parenting stress levels (primary independent variable) controlling for age and maternal smoking status. Models evaluating DNAm in children also controlled for sex of the child. All analyses were conducted in the R statistical computing environment controlling for cellular proportions significance was determined using a false discovery rate (FDR) of 0.05.

Results: Our maternal participants had a mean age of 32.35 years old and 24 percent indicated that they smoke cigarettes. The mean age of our children was 3.73 years old and 35 percent male. Significant variation in maternal DNA methylation in 95 CpG sites was associated with levels of parenting stress. Notably, the relationship between parenting stress and DNAm was inversely proportional at most sites (87%) had decreased DNAm with higher levels of parenting stress. Notably, we identified a change in DNAm associated with poly(ADP-ribose) polymerase-1 (PARP-1), which plays a key role in stress signaling. We did not identify any significant association with child DNAm related to maternal parenting stress. However, the observed DNAm patterns in the children mirrored DNAm patterns observed in their mothers.

Conclusion: Our study results suggest that parenting stress is associated with differential DNAm in mothers experiencing higher levels of parenting stress. Since the study did not collect multiple samples for DNAm over time, it is unclear if the DNAm differences observed were a direct result of parenting stress or were pre-existing differences that contribute to the mother’s response or perceived level of parenting stress. Altered DNAm in PARP-1 warrants further follow-up as the gene is known to play a key role in cellular function and response to stress. Alterations in the PARP-1 gene have been associated with genome instability, shorter lifespans, and spontaneous tumors in animal models (Luo & Kraus, 2012). Further studies are needed to determine if differences in DNAm at PARP-1 are associated with altered protein production or other measureable health effects.