Beyond VO2max: Integrated Physiological Phenotyping and Candidate-Gene Analysis of Elite Versus Recreational Endurance Runners

Abstract

Background: Endurance performance reflects integrated cardiorespiratory, metabolic and musculoskeletal traits with substantial heritability, yet sex-balanced studies that simultaneously deep-phenotype athletes and genotype candidate loci against trained comparators remain scarce. Objective: We aim to characterize the integrated physiological profile and genotype distributions at five endurance-relevant polymorphisms in elite versus recreationally trained runners. Methods: Eighty runners (20 elite male, 20 elite female, 20 recreational male, 20 recreational female) completed graded treadmill testing with breath-by-breath gas exchange and capillary blood lactate sampling, together with whole-body dual-energy X-ray absorptiometry. A sub-sample of 40 participants (10 per subgroup) underwent next-generation sequencing of ACTN3 R577X, VEGFA rs699947, PPARGC1A Gly482Ser, ACE I/D and PPARG Pro12Ala. Physiology was compared using one-way ANOVA with Tukey’s HSD and Cohen’s d; genotype distributions were compared using Monte Carlo exact tests with Benjamini–Hochberg correction. Results: Elite runners exhibited higher VO2max (elite male 71.8 ± 4.9; elite female 65.3 ± 3.6 mL·kg−1·min−1; both vs. same-sex controls, p < 0.001; η2 = 0.62), superior running economy (η2 = 0.76), lactate thresholds shifted rightward by ~1 km·h−1, and more favorable body composition (lean mass η2 = 0.80; body fat η2 = 0.48). Principal component analysis separated elites from recreational runners along PC1 (40.1% variance) in both sexes. Effect-allele frequencies were numerically higher in elites at every locus (odds ratios 1.48–2.03), but no genotype × group association survived correction (all q ≥ 0.82). Conclusions: Elite endurance status was robustly distinguished by an integrated physiological phenotype with large effect sizes. Effect-allele frequencies at five candidate loci were numerically higher in the expected direction but did not reach statistical significance; given the small genotyped sub-sample, these genetic data are purely exploratory and hypothesis-generating and require replication in adequately powered cohorts.