One Athlete, Many Answers: Genetic Testing Alone Fails to Predict Football Performance

A single elite footballer has become the most comprehensively profiled athlete with differences of sex development (DSD) ever described in the scientific literature, and the results challenge a core assumption behind some of the most contentious eligibility rules in world sport. In a case report published in Frontiers in Sports and Active Living, an international team led by Yannis Pitsiladis of Hong Kong Baptist University reports that genetic markers, hormone levels and actual athletic performance did not line up neatly in one athlete. Instead, the 20-year-old Ghanaian national-team player showed a strikingly mixed physiological profile: explosive sprinting and jumping power that exceeded elite female football reference values, alongside strength, lung function and aerobic capacity that sat broadly within the female range.

The study arrives at a politically charged moment. Recent eligibility frameworks in women’s sport, including proposals for sex-determining region Y (SRY) gene screening, have focused attention on single biological markers as the basis for classification. Yet the relationship between such markers and sport-specific performance has remained poorly documented, particularly for athletes with DSD, an umbrella term covering congenital conditions in which chromosomal, gonadal, endocrine and anatomical sex characteristics do not align in typical patterns. The researchers argue that no single genetic or hormonal measurement can reliably predict how fast, strong or enduring an athlete will be on the pitch.

The participant, a 20-year-old competing at national-team level in women’s football, had never undergone formal genetic assessment before enrolling in the study. She reported no chronic disease, no medication or supplement use, and her only relevant medical history was a knee ligament strain that did not restrict testing. To protect her identity, the authors withheld her club, playing position and other potentially identifying details. Every planned assessment was completed without adverse events, and no therapeutic intervention was administered; the investigation was purely observational and cross-sectional.

Whole-genome sequencing, performed on the MGI DNBSEQ-T1x platform at an average depth of 51.3-fold, revealed a 46,XY chromosomal complement with the SRY locus present. Crucially, the analysis also identified a homozygous missense variant in the SRD5A2 gene, c.578A>G (p.Asn193Ser), classified as pathogenic in ClinVar and predicted deleterious by multiple computational tools. This gene encodes 5α-reductase type 2, the enzyme responsible for converting testosterone into dihydrotestosterone (DHT), the more potent androgen that drives many aspects of male-typical development. Genome-wide screening flagged six pathogenic or likely pathogenic variants in total, but only the SRD5A2 variant related to the athlete’s clinical picture; targeted evaluation of two published DSD gene panels, covering 171 and 267 genes respectively, found nothing else of significance.

The endocrine profile told a consistent biochemical story. Total testosterone measured 23.6 nmol per litre, well above typical female reference intervals, while DHT was only 0.80 nmol per litre, producing a testosterone-to-DHT molar ratio of 29.5:1. That disproportionate ratio is the biochemical signature of impaired 5α-reductase activity, confirming the molecular diagnosis. Luteinizing hormone and follicle-stimulating hormone were also elevated, a pattern seen when downstream androgen signalling is blunted. Yet the athlete’s oestradiol, progesterone and androstenedione levels, along with her sex hormone-binding globulin, painted a more nuanced picture that aligned with neither a typical female endocrine profile nor a eugonadal male one.

Physical testing exposed the mismatch between biology and performance. Countermovement jump height of 41.9 centimetres exceeded the means of both under-18 (30.0 centimetres) and first-team (32.3 centimetres) elite female football squads by large margins, corresponding to z-scores of 4.25 and 2.82, while remaining well below male position-specific references. Her best 30-metre sprint time was faster than both elite female reference groups and closely aligned with professional male first-division values. In sharp contrast, maximal isometric knee-extensor torque of 203 newton-metres was almost identical to the cisgender female comparator mean and below both cisgender male and transgender female cohort means. Isokinetic strength results fluctuated by contraction mode and velocity, sometimes matching female squad averages and sometimes falling well short of them.

Aerobic and respiratory measures continued the pattern of heterogeneity. Relative VO2max of 48.7 millilitres per kilogram per minute, measured directly by breath-by-breath gas analysis during a treadmill ramp test, sat slightly above elite female football reference means but far below male position-specific values, with z-scores between roughly minus three and minus four. Forced vital capacity and forced expiratory volume in one second were lower than every comparator group in absolute terms, corresponding to 85 and 90 percent of predicted values, although the elevated FEV1/FVC ratio of 0.94 indicated preserved expiratory flow. On the field, she covered 440 metres on the Yo-Yo Intermittent Recovery Test Level 2, within the reported range for elite female cohorts and below male references, under moderate heat stress recorded at a wet-bulb globe temperature of 27.79 degrees Celsius.

Body composition added further nuance. Dual-energy X-ray absorptiometry on a Hologic Horizon scanner showed elevated lumbar spine bone mineral density of 1.37 grams per square centimetre, low adiposity with 11.6 kilograms of fat mass, and an intermediate fat-free mass of 48.7 kilograms. Cross-calibration equations, applied because comparator groups were scanned on a GE Lunar Prodigy system, strengthened rather than reversed these findings. Against published elite female football data, her bone density, body fat percentage and lean mass all fell within reported ranges, while relative to elite male squads she showed higher body fat and lower absolute lean mass. The authors note that her self-reported training volume of 9,813 MET-minutes per week, roughly 2.3 to 2.4 times that of the recreationally active in-house comparator groups, likely contributes to some laboratory advantages, though core performance benchmarks came from training-matched elite cohorts.

The research team is careful about what the case can and cannot show. A single-athlete, cross-sectional design cannot establish that 46,XY DSD, the SRD5A2 variant or the endocrine profile caused any element of the performance phenotype. The z-scores are descriptive comparisons sensitive to the means and sample sizes of source datasets drawn from Finnish, Norwegian, English and German cohorts collected between 1998 and 2023, differing in era, competition level and testing conditions. Family history and psychosocial data were not collected, and the authors acknowledge a residual risk of deductive re-identification given the rarity of the condition, which constrained how much detail could be published. They explicitly state that the data do not allow inference that the endocrine profile explains the observed differences between sprint, strength and aerobic outcomes.

Still, the implications for policy are pointed. As governing bodies move toward genetic screening, the case demonstrates that genotype, endocrine status and sport-specific performance phenotype may diverge substantially within a single athlete, and that football performance depends on multiple interacting domains rather than one trait. The athlete herself consented voluntarily and expressed hope that such studies would contribute to a more evidence-based understanding of DSD in sport. The authors call for the systematic accumulation of multidimensional, sport-specific physiological datasets, arguing that this rare kind of natural biological variation deserves the same scientific scrutiny that human-performance research traditionally reserves for training, technology and pharmacology. Until such datasets exist, they contend, isolated markers like an SRY result reveal far less about athletic capability than the biology of performance itself.

Subject of Research: Integrated genetic, endocrine and sport-specific performance profiling of an elite footballer with 46,XY differences of sex development

Article Title: Case Report: Integrated physiological and performance profiling of an elite athlete with differences of sex development

Article References: Hu, K., Huang, K., Xu, X., Hamilton, B. R., Rozenštoka, S., Pigozzi, F., Ling, S. K.-K., Cheung, A. S., Vilain, E., & Pitsiladis, Y. P. (2026). Case Report: Integrated physiological and performance profiling of an elite athlete with differences of sex development. Frontiers in Sports and Active Living, 8, Article 1906817. https://doi.org/10.3389/fspor.2026.1906817

Image Credits: AI Generated

DOI: 10.3389/fspor.2026.1906817

Keywords: differences of sex development, DSD, SRD5A2, testosterone, dihydrotestosterone, athlete eligibility, whole-genome sequencing, VO2max, sprint performance, women's football, sports physiology, SRY gene testing