# Caregiver-child interaction and early childhood development among preschool children in rural China: the possible role of blood epigenome-wide DNA methylation

## TL;DR

This study explores how DNA methylation in blood may link caregiver-child interactions to early childhood development in rural Chinese preschoolers.

## Contribution

It provides population-level epigenetic evidence that DNA methylation may mediate the impact of parenting on child development.

## Key findings

- 844 CpG sites were significantly associated with children's global neurodevelopmental scores.
- 395 CpG sites mediated the link between caregiver-child interaction and early childhood development.
- Several genes linked to neurodevelopment were associated with top CpG sites.

## Abstract

While the association between caregiver-child interaction and early childhood development (ECD) has been observed, the underlying biological mechanism remains to be elucidated.

This study aimed to examine the potential role of epigenome-wide DNA methylation in the association between caregiver-child interaction and ECD among preschool children living in rural China.

This study was conducted in a rural area in Central China. ECD was evaluated with the Gesell Development Diagnosis Scale (Chinese version), yielding a developmental quotient (DQ), i.e. global neurodevelopmental score (NDS). Caregiver-child interaction was assessed using the Brigance Parent-Child Interaction Scale. Of the 171 children aged 3–6 years who participated in ECD assessment and blood samples collection, a total of 64 were selected for epigenome-wide association study with Illumina Infinium MethylationEPIC v1.0 BeadChip array (850 K). The linear regression model in the R package “CpGassoc”was applied to identify CpG sites associated with global NDS and caregiver-child interaction. The causal inference test (CIT) was utilized to explore the potential mediation effect of DNA methylation.

Our epigenome-wide DNA methylation analysis revealed 844 CpG sites significantly associated with children’s global NDS (PFDR<0.05), while no CpG sites were found to be directly related to caregiver-child interaction after FDR correction. Mediation analysis indicated that 395 CpG sites mediated the association between caregiver-child interaction and children’s ECD before FDR correction; and among the genes with top 20 CpG sites, genes CFAP45 (cg07740897), PCDH9 (cg20666533), LAMC3 (cg14447608), FAM19A5 (cg13192640), PRKG1 (cg09071556), PLEKHG5 (cg05151739), TCERG1 (cg09189322), and MTRR (cg08075506) have been reported to be associated with neurodevelopment and related diseases.

Blood DNA methylation may mediate the association between caregiver-child interaction and ECD in preschool children. This provides population-level epigenetic evidence supporting parenting interventions for vulnerable preschool children who experience poor caregiver-child interaction, aiming to ensure optimal early development potential. However, future studies in diverse populations are needed to validate these findings.

The online version contains supplementary material available at 10.1186/s12864-025-11406-2.