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Genetic predisposition to lower physical activity (PA) is linked to higher cardiometabolic disease risk. This study used PA polygenic risk scores (PRS) to explore these genetic links in a large Finnish cohort.

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Area of Science:

  • Genetics
  • Cardiology
  • Public Health

Background:

  • Genetic pleiotropy suggests shared genes influence multiple traits, potentially explaining the link between physical activity (PA) and reduced disease risk.
  • Observed associations between high PA and lower morbidity/mortality warrant investigation into underlying genetic mechanisms.

Purpose of the Study:

  • To investigate the associations between physical activity polygenic risk scores (PA PRS) and cardiometabolic diseases.
  • To explore the genetic underpinnings of the relationship between PA and health outcomes in the Finnish population.

Main Methods:

  • Utilized a FinnGen study cohort of 218,792 individuals with genome-wide genotyping and health register data.
  • Adapted PA PRS for device-measured overall PA.
  • Analyzed associations between PA PRS and body mass index, diseases, and mortality using linear and logistic regression models.

Main Results:

  • A higher PA PRS was associated with a lower body mass index (β = -0.025 kg·m⁻², P = 1.87 × 10⁻⁸⁰).
  • PA PRS predicted lower risk for cardiovascular diseases (OR = 0.95, P = 9.5 × 10⁻¹⁹), hypertension (OR = 0.93, P = 2.7 × 10⁻⁴⁴), type 2 diabetes (OR = 0.91, P = 4.1 × 10⁻⁴²), and coronary heart disease (OR = 0.95, P = 1.2 × 10⁻⁹).
  • Higher PA PRS was also linked to reduced overall mortality risk (OR = 0.97, P = 0.0003).

Conclusions:

  • Individuals with a genetic predisposition for lower physical activity face a higher risk of cardiometabolic diseases.
  • Inherited mechanisms related to physical fitness and metabolism may influence both PA levels and cardiometabolic disease risk.
  • Genetic factors may partially explain the observed link between lower PA and increased disease/mortality risk.