Associations between surrogates of prenatal lead DNA methylation and adolescent neural network architecture

This is the authors' abstract. We don't add key points for this paper.

Lead (Pb) is a potent neurotoxicant that can adversely affect health and cognitive function. This study used an epigenetic score of prenatal Pb exposure to assess associations between lead-related methylation and brain structure in adolescents. We studied 181 adolescents from the Study in Adolescent Neural Development (SAND), a subsample of the Future of Families and Child Wellbeing study, part of a longitudinal cohort with significant representation of marginalized youths. Potential prenatal Pb exposure was computed based on DNA methylation (DNAm) samples collected at ages 9 and 15. Diffusion MRI scans were collected at age 15 and used to produce white matter connectivity network metrics: small-world propensity, global efficiency, modularity, and transitivity. A higher prenatal DNAm Pb score at age 9 was linked to decreased structural global network efficiency in adolescence (β = -0. 26, p = .017), transitivity (β = -0.22, p = 0.04), small-world propensity (β = -0. 246, p = .02), as well as increased modularity (β = 0.179, p = 0.03) . Age 9 Pb methylation scores were particularly linked to network efficiency where the connections to and from the frontal orbital subnetwork were individually excluded. This suggests that this subnetwork is particularly important in the association between structural brain networks and surrogates of prenatal Pb exposure. Results indicate that a DNA methylation surrogate of prenatal lead exposure is associated with differences in white matter connectivity organization.