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<p>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: <i>P</i> = 1.3 × 10^−85; W-AIG: <i>P</i> = 6.67 × 10<sup>−4</sup>). 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, <i>P_FDR</i> = 8.21 × 10<sup>−33</sup>; W-AIG: OR = 24.51, 95% CI 23.47–25.56, <i>P_FDR</i> = 8.97 × 10<sup>−3</sup>), whereas those with high genetic risk but favorable lifestyles had reduced odds (UKB: OR = 2.13, 95% CI 2.00-2.25, <i>P_FDR</i> = 2.32 × 10<sup>−9</sup>; W-AIG: OR = 3.92, 95% CI 3.11–4.73, <i>P_FDR</i> = 0.19). These findings suggest that maintaining a healthy lifestyle may help reduce obesity risk even among individuals with strong genetic predisposition.</p>

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Modifiable lifestyle factors and genetic risk of obesity in Indians

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Emadeldin Hassanin,
  • Rakesh Kalapala,
  • Nitin Jagtap,
  • Ravikanth Vishnubhotla,
  • Nikhilesh Andhi,
  • Sandeep Mamidi,
  • Shree Vyshnavi,
  • Srikanth Jilla,
  • Mithil Samudrala,
  • P. Shravani Shriya,
  • Kamaldeep Chawla,
  • Carlo Maj,
  • Patrick May,
  • Dheeraj Reddy Bobbili,
  • D. Nageshwar Reddy

摘要

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.