Deciphering V̇_O: limits of the genetic approach

Area of Science:

• Exercise Physiology
• Human Genetics
• Molecular Biology

Background:

• Maximal oxygen consumption (V̇O2max) is a critical determinant of endurance performance and a predictor of cardiovascular health.
• V̇O2max exhibits significant heritability (>50%) and substantial inter-individual variability in both sedentary states and response to exercise training.
• Despite its importance, genetic studies have not identified specific genetic markers for high V̇O2max or trainability.

Purpose of the Study:

• To propose a new framework for understanding the genetic basis of complex physiological traits like V̇O2max.
• To highlight the limitations of traditional genetic approaches in explaining multigenetic phenotypes.
• To suggest that V̇O2max and its trainability are emergent properties influenced by multiple biological layers.

Main Methods:

• Review and synthesis of existing literature on V̇O2max genetics, including candidate-gene, gene-expression, and GWAS studies.
• Conceptual proposal integrating transcriptomic networks, epistasis, epigenome, and epitranscriptome.
• Critical evaluation of the sufficiency of genetic approaches for complex traits.

Main Results:

• Previous genetic studies (candidate-gene, gene-expression, GWAS) have not successfully identified a distinct genetic signature for V̇O2max or trainability.
• The study posits that V̇O2max is an emergent property arising from complex interactions within biological systems.
• Heritability estimates indicate a strong genetic component, yet specific gene identification remains elusive.

Conclusions:

• A purely genetic approach is insufficient to fully elucidate the complex, multigenetic nature of V̇O2max and its trainability.
• Understanding V̇O2max requires considering emergent properties arising from transcriptomic networks, epigenetic modifications, and their interactions.
• Future research should adopt a more holistic, systems-biology approach to unravel the genetic and molecular underpinnings of V̇O2max.