Theoretical Framework for Understanding the Epigenetic Basis of Hypertension in West African Populations: Contributions from Nigerian Cohort Data

Hypertension in West African populations exhibits epidemiological characteristics that diverge from patterns observed in European cohorts, including earlier onset, greater severity, and differential pharmacogenomic responses to standard antihypertensive agents. These disparities remain inadequately explained by conventional behavioural and socioeconomic risk models, suggesting epigenetic mechanisms as an underexplored theoretical pathway. This study develops and tests a theoretical framework for understanding the epigenetic basis of hypertension in West African populations using a prospective cohort of 1,200 Nigerian adults aged 30 to 65 years recruited from six states representing all geopolitical zones. Genome-wide DNA methylation analysis is performed using Illumina EPIC arrays on peripheral blood samples at enrolment and repeated at three-year follow-up. Differentially methylated regions are identified using bioinformatic pipelines in R, and structural equation modelling in Stata tests the proposed epigenetic pathway model incorporating early life adversity, dietary sodium exposure, oxidative stress markers, and blood pressure trajectories. The Developmental Origins of Health and Disease theory and the Epigenetic Programming Framework provide the conceptual basis. Original theoretical contributions include a novel Contextualised Epigenetic Hypertension Model calibrated specifically to Nigerian population parameters, distinct from Eurocentric frameworks. Findings will advance mechanistic understanding of hypertension in West African populations and provide a basis for pharmacogenomically informed antihypertensive prescribing guidelines. Keywords: epigenetics, hypertension, West Africa, DNA methylation, Nigerian cohort.