This excerpt describes a study investigating teh relationship between mitochondrial DNA copy number (mtDNA-CN) and DNA methylation (DNAm) in children, and how thes factors relate to cognitive development. Here’s a breakdown of the key elements:
1. Study Population and Design:
The study involves children from a cohort in Mexico City.
Data was collected at multiple time points, including the 2nd trimester of pregnancy, birth, and at 48 months of age.
2. Measurements:
mtDNA-CN: Measured in cord blood.
DNAm: Measured in cord blood and at 48 months of age using the EPIC array.
Cognitive Function: Assessed at 48 months using the McCarthy Scales of Children’s Abilities (MSCA). The MSCA provides scores for motor, memory, perceptual-performance (perception), quantitative, and verbal skills, and also a General Cognitive Index (GCI or Cognition).
Covariates: A range of maternal and child characteristics were collected as potential confounders. these include:
Socioeconomic status (SES)
Maternal psychosocial stress (Negative Life Events – NLE)
Maternal age
pre-pregnancy BMI
parity
Education
Child sex
Birthweight z-scores
Gestational age
Cell-type proportions from DNAm data
Environmental tobacco smoke
3. Data Processing and Analysis:
mtDNA-CN Normalization: Values were normalized to account for differences in DNA extraction methods.
DNAm Data Filtering: Probes were removed based on location (X and Y chromosomes), sequence characteristics (non-CG dinucleotides), cross-hybridization potential, and proximity to common SNPs.
MitoCarta Annotation: CpGs were annotated based on overlap with genes in the MitoCarta 3.0 database, which contains details on mitochondrial-related genes.
Surrogate Variable Analysis (SVA): Surrogate variables were calculated to account for genomic inflation and unmeasured confounding.
Statistical Modeling: Robust regression using the limma package in R was used to assess the association between mtDNA-CN and DNAm. Models were adjusted for a comprehensive set of covariates.
Multiple Testing Correction: P-values were adjusted for the false finding rate (FDR) using the Benjamini-Hochberg method.
4. Key Research Questions (inferred):
Does mtDNA-CN in cord blood predict DNAm patterns in cord blood and/or at 48 months of age?
Are there specific DNAm sites (notably those related to mitochondrial function) that are associated with mtDNA-CN?
How do mtDNA-CN and dnam relate to cognitive development in children?
* Are these associations influenced by environmental factors and maternal characteristics?
this study aims to understand the complex interplay between mitochondrial function (as reflected by mtDNA-CN), epigenetic modifications (DNAm), and cognitive development in children, while carefully considering potential confounding factors.