Epigenome-Wide Association Study of Maternal Nutrition and Offspring Metabolic Outcomes in a Nigerian Birth Cohort

The developmental origins of health and disease (DOHaD) hypothesis proposes that maternal nutritional status during pregnancy epigenetically programmes offspring metabolic phenotypes with long-term health consequences. Epigenome-wide association studies (EWAS) of maternal nutrition and offspring metabolic outcomes have not been conducted in any sub-Saharan African birth cohort, leaving a significant gap in understanding epigenetic programming in low and middle-income country contexts. This dissertation conducted an EWAS of maternal nutrition and offspring metabolic outcomes in a prospective Nigerian birth cohort from Ogun State, South West Nigeria. Eight hundred mother-offspring pairs were enrolled at the Olabisi Onabanjo University Teaching Hospital antenatal clinic. Maternal dietary intake was assessed using a validated 24-hour dietary recall and food frequency questionnaire during the second trimester. Offspring cord blood and follow-up venous blood at 24 months were subjected to genome-wide DNA methylation profiling using the Illumina EPIC array. Offspring metabolic outcomes including BMI z-score, fasting glucose, and serum lipids were assessed at 24 months. Methylation sites in imprinted gene regions (IGF2, H19) and lipid metabolism gene promoters were significantly associated with maternal protein intake and offspring BMI z-score at follow-up. These EWAS findings provide the first epigenetic evidence for nutritional programming in Nigerian offspring. Keywords: EWAS, maternal nutrition, epigenetic programming, birth cohort, Nigeria