Genomic and transcriptomic predictors of response levels to endurance exercise training

Predicting the responsiveness to regular exercise is a topic of great relevance due to its potential role in personalized exercise medicine applications. The present review focuses on cardiorespiratory fitness (commonly measured by maximal oxygen uptake, VO₂max), a trait with wide-ranging impact on health and performance indicators. Gains in VO₂max demonstrate large inter-individual variation even in response to standardized exercise training programs. The estimated delta VO₂max heritability of 47 % suggests that genomic-based predictors alone are insufficient to account for the total trainability variance. Candidate gene and genome-wide linkage studies have not significantly contributed to our understanding of the molecular basis of trainability. A genome-wide association study suggested that VO₂max trainability is influenced by multiple genes of small effects, but these findings still await rigorous replication. Valuable evidence, however, has been obtained by combining skeletal muscle transcript abundance profiles with common DNA variants for the prediction of VO₂max response to exercise training. Although the physiological determinants of VO2max measured at a given time are largely enunciated, what is poorly understood are the details of tissue-specific molecular mechanisms that limit VO₂max and related signalling pathways in response to exercise training. Bioinformatics explorations based on thousands of variants have been used to interrogate pathways and systems instead of single variants and genes, and the main findings, along with those from exercise experimental studies, have been summarized here in a working model of VO₂max trainability.

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