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Updated: Apr 11, 2026

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
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Obesity, physical activity, and gene-environment interactions: a natural experiment framework.

Lei Liu1,2,3,4, Xuxiu Zhuang1,3, Haonan Zhou1,3

  • 1Health Sciences Institute, China Medical University, Shenyang, 110122, Liaoning Province, PR China.

Journal of Health, Population, and Nutrition
|April 10, 2026
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Summary

Physical activity (PA) significantly mitigates genetic predisposition to obesity in Chinese youth. Higher PA levels lessened the impact of genetic risk scores on BMI trajectories over four years.

Keywords:
Children and adolescentsGenetic susceptibilityGene–environment interactionOverweight and obesityPhysical activity

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Area of Science:

  • Obesity research
  • Genetics and public health
  • Behavioral science

Background:

  • Obesity arises from complex gene-environment interactions.
  • Physical activity (PA) is a key intervention for obesity.
  • This study examined PA's role in modifying genetic obesity risk in Chinese youth.

Purpose of the Study:

  • To investigate how physical activity (PA) influences the association between genetic predisposition and obesity.
  • To analyze gene-PA interactions on body mass index (BMI) trajectories in Chinese youth.

Main Methods:

  • A 4-year longitudinal natural experiment with 591 Chinese youth.
  • Categorized participants into high-PA (HPA) and low-PA (LPA) groups based on curriculum.
  • Calculated weighted genetic risk scores (WGRSs) and analyzed BMI changes using generalized linear mixed models.

Main Results:

  • Weighted genetic risk scores (WGRSs) predicted baseline obesity (0.21 kg/m² higher BMI per unit increase).
  • BMI increases were smaller in the HPA group compared to the LPA group over the study period.
  • Significant WGRS-PA interactions showed that higher genetic risk individuals benefited more from sustained PA in reducing BMI.

Conclusions:

  • A significant interaction between PA levels and WGRS was identified in modifying BMI trajectories.
  • Genetic susceptibility plays a crucial role in determining the effectiveness of long-term PA in managing BMI progression among Chinese youth.