Epigenetic Mechanisms Linking Early Life Nutritional Exposures to Chronic Disease Risk in Nigerian Populations: A Conceptual and Empirical Investigation

The developmental origins of health and disease hypothesis proposes that early life nutritional exposures during critical windows of development programme epigenetic modifications that influence chronic disease susceptibility across the lifespan. While this field is advancing in high-income countries, empirical data from African populations including Nigeria remain critically scarce. This study investigated epigenetic mechanisms linking early life nutritional exposures to chronic disease risk in Nigerian populations, combining a theoretical synthesis with original empirical work conducted in Enugu, Ibadan, and Kano. A nested case-control design was embedded within an existing birth cohort, with 200 mother-child pairs assessed at delivery and followed for five years. Maternal nutritional biomarkers at third trimester were linked to neonatal epigenetic profiles derived from cord blood DNA methylation analysis at candidate gene loci relevant to adipogenesis, insulin signalling, and inflammatory pathways. Child cardiometabolic risk markers were assessed at age five. Mediation analysis and structural equation modelling were applied. Results showed that maternal micronutrient deficiency, specifically folate and vitamin B12, was associated with differential methylation at metabolic gene loci. Altered methylation patterns at birth predicted elevated BMI-for-age and insulin resistance at age five. These relationships were partially mediated by postnatal dietary quality. This study makes an original theoretical and empirical contribution to the emerging field of nutritional epigenetics in sub-Saharan Africa. Keywords: epigenetics, early nutrition, chronic disease, developmental origins, Nigerian populations