DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort

Background and Aim Prenatal exposure to indoor air pollution (IAP) has been linked neurodevelopmental delay in toddlers. Changes DNA methylation (DNAm) have independently associated with both prenatal delayed neurodevelopment. Investigating DNAm as a mediator may help elucidate the biological pathways driving association between IAP delay. In this study, we aim identify differentially methylated CpG sites gene regions that mediate association. Methods We analyzed data from 142 mother-child pairs enrolled South African Drakenstein Child Health Study. cord blood was measured using Infinium MethylationEPIC HumanMethylation450 arrays. Particulate matter an aerodynamic diameter of 10m or less (PM10) inside participants’ homes during second trimester pregnancy. Neurodevelopment assessed at age 2 years Bayley Scales Infant Toddler Development III four domains (cognitive function, general adaptive behavior, language, motor function). used three high-dimensional mediation analysis techniques (HIMA, DACT gHMA) potential mediators, complemented causal assess robustness our results. Results Differential 29 4 (GOPC, RP11-74K11.1, DYRK1A, RNMT) found significantly PM10 cognitive Estimated proportion mediated (95%-confidence interval) ranged 0.29 (0.01,0.86) for cg00694520 0.54 (0.11,1.56) cg05023582. Conclusions DYRK1A several genes mapped to, including CNKSR1, IPO13, IFNGR1, LONP2, CDH1 are implicated neurodevelopment identified (cg23560546, cg22572779, cg15000966) previously fetal brain development. These findings suggest Keywords: particulate matter, neurodevelopment, blood, epigenetics, newborn