Modifiable lifestyle factors and genetic risk of obesity in Indians

This study investigates whether sustained adherence to a healthy lifestyle is associated with lower obesity risk among individuals of Indian ancestry who have a high polygenic risk score (PRS) for body mass index (BMI). For the purposes of this research, a health-promoting lifestyle is defined by routine physical activity, non-smoking or minimal smoking behavior, and adherence to a balanced diet. We analyzed two independent cohorts: 6,663 Indian participants from the UK Biobank and 91 participants from the Wellytics-Asian Institute of Gastroenterology cohort. Genetic predisposition was quantified using a BMI-PRS, while lifestyle behaviors were combined into a composite score categorized as favorable or unfavorable. Obese individuals exhibited significantly higher PRS values than non-obese counterparts (UKB: P = 1.3 × 10^-85; W-AIG: P = 6.67 × 10⁻⁴). Participants with both a high PRS and an unfavorable lifestyle showed the greatest odds of obesity (UKB: OR = 3.01, 95% CI 2.92-3.11, P_FDR = 8.21 × 10⁻³³; W-AIG: OR = 24.51, 95% CI 23.47-25.56, P_FDR = 8.97 × 10⁻³), whereas those with high genetic risk but favorable lifestyles had reduced odds (UKB: OR = 2.13, 95% CI 2.00-2.25, P_FDR = 2.32 × 10⁻⁹; W-AIG: OR = 3.92, 95% CI 3.11-4.73, P_FDR = 0.19). These findings suggest that maintaining a healthy lifestyle may help reduce obesity risk even among individuals with strong genetic predisposition.