Cardiorespiratory Fitness, Body Composition, Diabetes, and Longevity: A 2-Sample Mendelian Randomization Study

Area of Science:

• Genetics
• Cardiology
• Metabolic Health

Background:

• Cardiorespiratory fitness, measured as maximal oxygen consumption (VO2max), is a key indicator of health and longevity.
• Understanding the causal factors influencing VO2max is crucial for public health strategies.

Purpose of the Study:

• To investigate the causal relationships between VO2max and various factors including body composition, physical activity, diabetes, and performance enhancers.
• To determine the directionality of these associations using Mendelian randomization.

Main Methods:

• A bidirectional 2-sample Mendelian randomization (MR) study was employed using large-scale genome-wide association study data.
• Multivariable MR (MVMR) was used to assess independent causal effects.
• VO2max was estimated from submaximal cycle tests and adjusted for body weight and fat-free mass.

Main Results:

• Higher body fat percentage was causally associated with lower VO2max.
• Increased appendicular lean mass, physical activity, and certain performance enhancers (fasting insulin, hematocrit, free testosterone) were positively associated with higher VO2max.
• VO2max did not show a causal association with type 2 diabetes, but body fat percentage and type 2 diabetes influenced longevity.

Conclusions:

• Cardiorespiratory fitness is modifiable through improvements in body composition and increased physical activity.
• While VO2max predicts mortality, it is not causally linked to type 2 diabetes or longevity.