Epigenetics of Developmental Disorders

Epigenetic features of developmental disorders in African children remain largely undescribed despite high and variable exposure burdens. We aimed to quantify blood-based epigenetic differences and their links to environmental exposures in Nigerian children. In a matched case–control study across Aminu Kano Teaching Hospital (Kano), University of Abuja Teaching Hospital (Abuja), Lagos University Teaching Hospital (Lagos) and University of Nigeria Teaching Hospital (Enugu), we enrolled 180 children aged 3–10 years between 1 March 2023 and 31 May 2025: cases (n=90; autism spectrum disorder [ASD] n=30, attention-deficit/hyperactivity disorder [ADHD] n=30, intellectual disability [ID] n=30) and matched controls (n=90). Genome-wide DNA methylation (Illumina EPIC), targeted histone marks (ChIP-qPCR), and small RNA sequencing were analysed in R 4.3.0 (minfi/limma/DMRcate; FDR<0.05). Primary result: global 5-methylcytosine was lower in cases (mean 4.8%±0.4) than controls (5.2%±0.5); ANOVA F(3,176)=9.02, p<0.001; mean difference −0.4%. Fifteen differentially methylated positions (Δβ 5–8%; including NR3C1 +7.4%, p<0.001) passed FDR. H3K9 acetylation was reduced (~15%) in cases, t(178)=−3.45, p=0.0007. MicroRNAs differed by diagnosis (e.g., let-7d lower in ADHD, fold-change 0.30, p=0.002; miR-145-5p higher in ASD, 1.7-fold, p<0.01). In multivariable logistic regression, higher methylation (OR 0.66 per +1% [95% CI 0.52–0.84], p=0.001), higher H3K9ac (OR 0.80 [0.68–0.95], p=0.014), higher let-7d (OR 0.88 [0.78–0.99], p=0.047), and lower blood lead (OR 1.25 per +1 µg/dL [1.12–1.39], p<0.001) independently predicted case status; AUC=0.81. An interaction was indicated, with ~9.5-fold higher odds for low methylation and lead levels greater than five µg/dL (95% CI 4.0–22, p = 0.01). In interviews (n = 15), parents described routine exposure to soot, proximity to landfills or smelters, and economic hardship. A concise, measurable epigenetic–toxicant profile identified Nigerian children with developmental disorders and points to modifiable risk.