Epigenetic Mechanisms Linking Early Life Adversity to Adult Cardiometabolic Disease Risk in a Prospective Birth Cohort in Ibadan, South West Nigeria

Early life adversity, including prenatal nutritional deprivation, household poverty, and childhood infection burden, is increasingly recognised as a programmable determinant of adult cardiometabolic disease risk through epigenetic pathways. This study investigates the epigenetic mechanisms linking early life adversity to adult cardiometabolic disease risk in a prospective birth cohort drawn from the Ibadan Pregnancy Cohort Study in South West Nigeria, followed longitudinally from birth to age 25. A nested case-control design within the cohort selects 400 participants (200 with cardiometabolic risk indicators and 200 matched controls) for detailed epigenetic profiling. Genome-wide DNA methylation analysis using Illumina EPIC arrays is applied to blood specimens, with differentially methylated regions identified using the R minfi and limma packages. Cardiometabolic outcomes including hypertension, insulin resistance, dyslipidaemia, and central adiposity are assessed through clinical measurements and fasting biochemistry. Structural equation modelling in R tests early life adversity scores as predictors of epigenetic age acceleration (Horvath and GrimAge clocks) and downstream cardiometabolic risk markers. The Developmental Origins of Health and Disease framework and Epigenetic Programming Theory provide the theoretical basis. Original contributions include the first genome-wide epigenetic analysis in a Nigerian birth cohort and a validated pathway model linking childhood poverty to adult cardiometabolic risk. Findings will advance translational epidemiology and inform early life intervention design. Keywords: epigenetics, early life adversity, cardiometabolic risk, birth cohort, South West Nigeria.