Uncovering the Mechanisms of Gene-Diet Interactions in Obesity Susceptibility Among Nigerian Adults: A Nutrigenomics Approach

The aetiology of obesity involves complex gene-diet interactions that modulate individual responses to dietary patterns and contribute to differential obesity susceptibility. Nutrigenomics, the science of how diet interacts with individual genetic variation to influence health, remains underdeveloped in the context of Nigerian and African genetic backgrounds. This study investigated mechanisms of gene-diet interactions in obesity susceptibility among Nigerian adults using a nutrigenomics approach, with recruitment conducted across research centres in Lagos, Enugu, and Kano. A case-control design enrolled 300 obese adults matched with 300 lean controls of comparable age, sex, and geographic origin. Whole-exome sequencing was performed on all participants to identify common obesity-associated single nucleotide polymorphisms. Dietary intake was assessed using a validated culturally adapted food frequency questionnaire, and major dietary patterns were derived through factor analysis. Gene-diet interaction analyses were conducted using regression models with multiplicative interaction terms, with correction for population stratification and multiple testing. Results revealed significant interactions between the FTO rs9939609 variant and Western dietary pattern adherence in modifying obesity risk. Carriers of the risk allele who consumed high-fat, high-sugar diets showed a three-fold elevated obesity odds compared to non-carriers on similar diets. Protective gene-diet interactions were identified between a flavonoid-rich traditional dietary pattern and a variant in the MC4R gene region. The study provides the first comprehensive nutrigenomics dataset from the Nigerian population and advances precision nutrition research for African populations. Keywords: nutrigenomics, gene-diet interaction, obesity, Nigerian adults, precision nutrition