Transgenerational Epigenetic Effects of Lead Exposure in Communities Near Mining Sites in Plateau State, North Central Nigeria

While the immediate health consequences of lead exposure in mining communities in Nigeria have been partially documented, the possibility that exposure in one generation may produce heritable epigenetic changes affecting subsequent generations remains entirely uninvestigated in the Nigerian context and represents a frontier in environmental health science. This dissertation investigates the potential transgenerational epigenetic effects of chronic lead exposure through a multigenerational study design in mining-affected communities in Barkin Ladi Local Government Area, Plateau State, North Central Nigeria. The study enrolled three-generational family units from lead-exposed and unexposed communities, comprising 320 grandparent-parent-offspring triads. Blood lead levels were measured in all enrolled participants using atomic absorption spectrophotometry. Whole blood DNA methylation profiling was conducted using reduced representation bisulfite sequencing, and differentially methylated regions were analyzed for associations with lead exposure levels, generation, and health outcomes including neurodevelopmental scores, growth indices, and immune function markers. Results revealed significant hypomethylation at fifteen genomic loci in lead-exposed grandparents, with partial methylation pattern persistence observed in unexposed grandchildren, suggesting potential epigenetic inheritance of lead-associated DNA methylation changes. Three differentially methylated regions mapped to genes involved in neurological development showed association with neurodevelopmental test scores in the third generation. The dissertation makes a pioneering contribution to the emerging field of environmental epigenetics in African populations and has significant implications for understanding the multigenerational health legacy of mining in Nigeria. Keywords: transgenerational epigenetics, lead exposure, mining communities, Plateau State, DNA methylation.