Modifiable lifestyle factors and genetic risk of obesity in Indians

This study investigates the potential for individuals of Indian ancestry with an increased polygenic risk score (PRS) for body mass index (BMI) to attenuate their risk of obesity through sustained adherence to a health-promoting lifestyle. For the purposes of this research, a health-promoting lifestyle is defined by routine physical activity, non-smoking or minimal smoking behavior, and the intake of a balanced nutritional 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 = 5.7 x 10^-27; W-AIG: P = 8.9 x 10^-3). Participants with both a high PRS and an unfavorable lifestyle showed the greatest odds of obesity (UKB: OR = 2.19, P = 3.01 x 10^-9; W-AIG: OR = 16.1, P = 2.99 x 10^-3), whereas those with high genetic risk but favorable lifestyles had reduced odds (UKB: OR = 1.58, P = 3.59 x 10^-3; W-AIG: OR = 3.10, P = 0.129). These findings underscore the potential of lifestyle interventions to attenuate genetically driven obesity risk in this population.