Deciphering the Interplay between Genetic Risk Scores and Lifestyle Factors on Individual Obesity Predisposition

Obesity's variability is significantly influenced by the interplay between genetic and environmental factors. We aimed to integrate the combined impact of genetic risk score (GRS_BMI) with physical activity (PA), sugar-sweetened beverages (SSB), wine intake, and eating habits score (EHS) on obesity predisposition risk. Adults' (n = 5824) data were analyzed for common obesity-related single nucleotide polymorphisms and lifestyle habits. The weighted GRS_BMI was constructed and categorized into quartiles (Qs), and the adjusted multivariate logistic regression models examined the association of GRS_BMI with obesity (BMI ≥ 30) and lifestyle factors. GRS_BMI was significantly associated with obesity risk. Each GRS_BMI unit was associated with an increase of 3.06 BMI units (p ≤ 0.0001). PA markedly reduced obesity risk across GRS_BMI Qs. Inactive participants' (≥90 min/week) mean BMI was higher in GRS_BMI Q3-Q4 compared to Q1 (p = 0.003 and p < 0.001, respectively). Scoring EHS ≥ median, SSBs (≥1 cup/day), and non-wine drinking were associated with higher BMI within all GRS_BMI Qs compared to EHS < median, non-SSBs, and non-wine drinkers. Mean BMI was higher in GRS_BMI Q4 compared to other quartiles (p < 0.0001) in non-wine drinkers and compared to Q1 for SSB's consumers (p = 0.07). A higher GRS_BMI augmented the impact of lifestyle factors on obesity. The interplay between GRS_BMI and modifiable lifestyle factors provides a tailored personalized prevention and treatment for obesity management.