Abstract
Understanding the role of epigenetic modifications in shaping phenotypic diversity is essential to unraveling complex traits and disease susceptibilities. African populations, including the Efik people of Cross River State, Nigeria, remain underrepresented in epigenetic research. This study investigates longitudinal epigenetic variation using a two-year follow-up of 300 individuals across three generations within the Efik community. We used high-throughput DNA methylation profiling (bisulfite sequencing), ATAC-seq, and RNA-seq to assess dynamic epigenetic changes. The analysis revealed that traditional dietary practices, environmental exposures, and socio-cultural norms significantly influenced methylation patterns and histone accessibility associated with immune responses and metabolic traits. Moreover, patterns consistent with transgenerational epigenetic inheritance were identified, particularly in loci associated with age-related diseases. These findings provide novel insights into population-specific epigenetic regulation and underscore the need for inclusive genomics research that integrates African diversity into global health paradigms.