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Chan, M. H.-M.

Publications and source records attributed to Chan, M. H.-M..

3 recordsLinked to original sources

Children's DNA Methylation and Family Dynamics in a Congo Basin Subsistence Community: Links with Parental Conflict and Fathers' Caregiving

Family environments may contribute to childrens long-term health through biological processes, including epigenetic regulation such as DNA methylation (DNAm). However, most studies in this area focus on Euro-American populations while also rarely including fathering data. The current study investigated childrens blood DNAm associations with positive (father caregiving) and negative (parental conflict) family dynamics in a smaller-scale subsistence society living in the Congo Basin rainforest. We measured DNAm from dried blood spots of 54 children (mean age=8.48 years) and conducted three epigenome-wide association studies aimed at discovering differential co-methylated regions (CMRs) associated with family dynamics. Via path models, we investigated the health implications and shared contribution of family factors of the identified CMRs. Differential DNAm associated with family dynamics was localized to genes related to stress, immunology, development, and aging, thus possibly linking to childrens physical health and were simultaneously connected to other family factors such as number of siblings. Our findings suggested similarities in biological embedding of family factors across socio-ecologically diverse contexts.

bioinformatics↗

Considerations for Cell Type Heterogeneity in Pediatric Salivary DNA Methylation Analyses: Comparison of Reference Panels & Stratification by Estimated Cell TypeProportion

Saliva is widely used in biomedical population research, including epigenetic analyses to investigate gene-environment interplay and identify biomarkers. Its minimally invasive collection procedure makes it ideal for studies in pediatric populations. Saliva is a heterogenous tissue composed of immune and buccal epithelial cells (BEC). Amongst the many epigenetic marks, DNA methylation (DNAm) is the most studied in human populations. Given DNAms integral role to cellular differentiation and maintenance, DNAm profiles are often highly cell type (CT)-specific and CT composition can drive salivary DNAm associations with environments or health as well as epigenetic age acceleration (EAA), discrepancy between chronological age and biological age derived from DNAm. To address this, reference-based CT deconvolution and statistically adjustment with estimated CT in DNAm analyses have become a common practice. However, it remains unclear how different CT reference panels--constructed from adult versus pediatric samples--affect DNAm results. Additionally, whether DNAm and EAA associations in saliva primarily originate from immune cells or BECs, or if they persist across saliva samples despite varying CT proportions, has yet to be examined. The current study used salivary DNAm samples obtained from 529 children (mean age=7.26 years, SD=0.26 years) in a community-based cohort, the Family Life Project. Our results highlighted the impact of estimated CT discrepancies across child and adult reference panels on DNAm associations. Upon stratifying the salivary DNAm samples into three subsamples--primarily BECs, primarily immune cells, and an approximately equal mix of both, we found significantly different EAAs across stratified samples when CT proportions were not accounted for. In both the context of DNAm and EAA associations, we detected stronger effects of cotinine concentrations, a tobacco smoke-exposure biomarker, in the subsample with primarily immune cells. We discussed the implications of our findings for the interpretation and replication of epigenetic research involving pediatric saliva samples.

bioinformatics↗

Cross-Tissue Specificity of Pediatric DNA Methylation Associated with Cumulative Family Adversity

BackgroundCumulative family adversity (cumulative FA), characterized by co-occurring stressors in a family context, may be biologically embedded through DNA methylation (DNAm) and contribute to later health outcomes. Materials & MethodsWe compared epigenome-wide DNAm associated with cumulative FA in buccal epithelial cells (BECs; n=218) and peripheral blood mononuclear cells (PBMCs; n=51) from 7-13-year-old children in Canada, accounting for sex, age, predicted cell-type proportion, and genetic ancestry. ResultsHigher levels of cumulative FA were associated with DNAm at seven sites, primarily in stress- and immune-related genes, only in PBMCs. Negative mother-child interaction contributed to this association. ConclusionsThe findings of this study suggested that PBMC DNAm can be used as a marker for biological embedding of cumulative FA.

genomics↗