Beyond VO<sub>2max</sub>: Integrated Physiological Phenotyping and Candidate-Gene Analysis of Elite Versus Recreational Endurance Runners.
Öncel HU, Siegler J, Özkan A, Oğul O, Yalçın M, Karabulut Ş et al. · Genes · 2026
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 2 = 0.62), superior running economy (η 2 = 0.76), lactate thresholds shifted rightward by ~1 km·h -1 , and more favorable body composition (lean mass η 2 = 0.80; body fat η 2 = 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.