The Impact of Genetic Polymorphisms on Training Response: Exercise Genetics Research on ACTN3, ACE, and EPAS1

Preface: A Scientific Bridge from the Laboratory to Taiwan’s Roads

Why do some people make rapid progress with the same training while others advance slowly? “Inter-individual variability” in training response is a core issue in exercise science, and the contribution of genetics cannot be ignored. Exercise genetics has identified several candidate genes with clear effects, among which ACTN3 (speed/power), ACE (endurance/cardiovascular), and EPAS1 (altitude/oxygen transport) are the most representative. Understanding them is not about labeling athletes, but about providing a scientific basis for individualized training and expectation management. This article will break down their molecular mechanisms and population epidemiology one by one.

ACTN3: The Molecular Truth of the Speed Gene

ACTN3 encodes α-actinin-3, which is specifically located at the Z-line of fast-twitch (Type II) muscle fibers. In the R577X polymorphism, the X allele introduces a premature stop codon, and XX homozygotes completely lack this protein (approximately 18% of the global population). Yang et al. (2003, AJHG) found that the XX genotype was extremely rare among elite Australian sprinters/power athletes, with no XX females among elite sprinters. Mechanistically, ACTN3 deficiency shifts fast-twitch muscle contractile properties slightly toward an endurance phenotype, with slightly reduced strength and power but potentially slightly improved fatigue resistance. The effect size is clear at the population level, but its predictive power for an individual athlete is limited—it is one factor among many, not a destiny-determining switch.

ACE I/D: Regulator of Endurance and Cardiovascular Function

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene affects ACE activity and circulating angiotensin II. The I allele is associated with lower ACE activity, and multiple studies (e.g., Montgomery et al. in British military personnel and mountaineers) have found the I type to be associated with endurance performance, high-altitude adaptation, and training-induced improvements in endurance, while the D type is biased toward power. However, the reproducibility of ACE studies is inconsistent across different populations, reminding us that single-gene effects are easily influenced by population structure and environmental interactions, and cross-population extrapolation requires particular caution.

EPAS1: An Evolutionary Imprint of High-Altitude Adaptation

EPAS1 (encoding HIF-2α) is a key transcription factor in the hypoxia-inducible factor pathway, regulating erythropoiesis and angiogenesis. The EPAS1 variants in Tibetan populations are a classic case of human high-altitude adaptation—they maintain lower hemoglobin levels at high altitude yet are less prone to chronic mountain sickness, a trait believed to originate from gene introgression from Denisovans. For sports, HIF pathway genes influence individual responses to altitude training, explaining why some people show marked increases in red blood cell production at altitude while others respond modestly. This has direct implications for individualizing altitude training plans.

Polygenic Scores: From Single Genes to Integrated Prediction

The predictive power of a single gene (e.g., ACTN3) is limited, which is why exercise genetics has shifted toward “polygenic scores”—a weighted sum of dozens to hundreds of relevant variants designed to estimate genetic predisposition more comprehensively. Research shows that scores combining multiple endurance- or power-related variants discriminate between elite and general populations better than any single gene. However, even polygenic scores currently lack sufficient predictive power for individual performance to replace actual testing—they can describe population trends but cannot accurately predict a specific person. This reminds us: genes are probability, not destiny. Polygenic scores are research tools and should not be commercialized as “talent identification.” What truly determines performance remains the degree to which one realizes genetic potential through training, nutrition, and psychology.

Gene–Environment Interaction: Training Is the Protagonist

Athletic performance is the product of “gene × environment” interaction, not determined by genes alone. The same genotype can yield vastly different performance outcomes under different training, nutritional, sleep, and psychological conditions. Although the HERITAGE study showed that training response is heritable, it also demonstrated that nearly everyone can improve through training—the difference lies only in magnitude. The practical implication for athletes is: rather than agonizing over “do I have talent genes,” focus on the controllable aspects of training quality and lifestyle. Genes set the “range” of potential, but most people are far from their upper limit, and training is the key to converting potential into results. For children and adolescents, long-term development and enjoyment should be emphasized, rather than premature conclusions based on genes.

The Ethical Red Lines of Sports Genetics

The application of sports genetics has clear ethical red lines that must not be crossed. The foremost red line is “no genetic screening of children”—using genes to determine a child’s sport specialization or to screen for “geniuses” is not only scientifically untenable (single or few genes have weak predictive power) but may also stifle interest, cause labeling, and inflict psychological harm. The second is “genetic privacy and anti-discrimination”—genetic data involves sensitive privacy and must be protected from inappropriate use by insurers, employers, or selection processes. The consensus statements of the international sports genetics community explicitly oppose using genetic testing for talent selection. The reasonable boundary of application is: genes may serve at most as “one of many references” for understanding individual recovery tendencies and injury risk, never as a verdict. Consumers should remain critical of exaggerated marketing from commercial “talent tests,” understanding that genes are probability rather than destiny, and that training and lifestyle are the controllable protagonists.

An Interdisciplinary Perspective: The Dialogue Between Genetics and Training Science

Sports genetics is a dialogue between genetics and training science, attempting to answer the eternal question of “how talent and effort jointly shape performance.” It reveals a balanced truth: genes set the range of potential, but training determines the realization of that potential. Research on genes such as ACTN3, ACE, and EPAS1 helps us understand part of the genetic basis of individual differences, but also clearly shows—the predictive power of single genes is limited, and athletic performance is a complex interaction of polygenic and environmental factors. This interdisciplinary perspective carries important practical and ethical implications: it helps us understand why some people respond quickly to the same training while others respond slowly (the heritability of training response), supporting the need for individualized training; but it also warns us against using genes to determine destiny or select talent. From an evolutionary angle (EPAS1’s high-altitude adaptation) to a molecular angle (ACTN3’s fast-twitch function), genetics provides deep mechanistic understanding of athletic performance. The rational integration of genetics and training science is: respect individual genetic differences, but place the emphasis on controllable training, nutrition, and lifestyle—because for the vast majority of people, the distance to their potential ceiling remains large, and the room for effort far exceeds the constraints of genes.

From Research to the Training Ground: A Framework for the Rational Use of Genetic Information

The rational use of sports genetic information can follow the “Understand—Reference—Monitor—Ethics” framework. Understand: recognize that athletic performance is a complex result of polygenic and environmental factors; there is no single “champion gene,” and genes are probability, not destiny. Reference: if you undergo genetic testing, treat the results as “one of many references” for understanding personal recovery tendencies, injury risk, and training preferences—not as a training prescription or a verdict on talent; for example, certain injury-related genes may indicate areas requiring attention. Monitor: let actual phenotypic data (power, lactate threshold, HRV, injury history) lead training decisions, as these guide daily practice better than genes; if you respond poorly to a plan, change the stimulus rather than blaming your genes. Ethics: firmly refuse to use genes to screen children or determine sport specialization (scientifically untenable and harmful to development), protect genetic privacy, and remain critical of exaggerated commercial “talent tests.” For Taiwanese parents, the pragmatic approach is to let children participate broadly and enjoy sports, with a focus on long-term development. The core of this framework is: genetics provides depth of understanding, but training and lifestyle are the controllable protagonists with enormous benefits—focusing on the latter is the right path to progress.

Local Applications in Taiwan: Climate, Events, and Cultural Context

Commercial sports genetic testing is already available in Taiwan, but it should be viewed rationally: a single gene only explains a small fraction of performance variation, with environment, training, nutrition, and psychology remaining the dominant factors. A more reasonable use of genetic testing is as a “reference for individualized expectations and training preferences,” rather than for screening child elites—the latter raises serious ethical concerns and is not scientifically justified. Taiwan lacks a permanent high-altitude training base; Hehuan Mountain (approximately 3,200 meters) can serve as a short-term altitude stimulus, but individual responses to altitude vary greatly. It is recommended to pair this with monitoring of blood markers (such as hematocrit and ferritin) rather than assuming it works for everyone.

Taiwanese parents are sometimes influenced by commercial genetic testing marketing and prematurely “channel” their children into specific sports. This is inadvisable both scientifically and educationally. Athletic talent development requires time, diverse experiences, and appropriate training. Premature genetic screening may actually stifle potential and interest. A rational approach is to let children participate broadly and enjoy sports, with a long-term development perspective—genes should be at most a reference, not a verdict.

Common Questions and Myth Clarification

Myth 1: Does the ACTN3 XX genotype mean you are unsuited for power events? No. The XX genotype shows slightly lower power output at the population level, but its predictive power for individuals is limited. Many other factors (training, psychology) matter more. A single gene should not be used to limit an individual.

Myth 2: Can genetic testing identify a child’s athletic talent? No. Athletic talent is a complex result of polygenic inheritance plus environment. Current testing is far from sufficient for prediction and should never be used to screen children.

Myth 3: Do endurance genes mean you don’t need to work hard? Genes only set a potential range. Most people are far from their potential ceiling—training is what turns potential into performance.

How to Read Sports Science Research: Developing Evidence Literacy

This article cites four studies from top international journals (such as Journal of Applied Physiology, Medicine & Science in Sports & Exercise, Sports Medicine, Nature, and Cell series), but as a reader, cultivating “evidence literacy” will help you absorb this knowledge more rationally rather than accepting it at face value. First, distinguish study types: randomized controlled trials (RCTs) have the strongest causal inference; observational studies (cohort, cross-sectional) can only show associations, not causation; animal and cellular studies reveal mechanisms but require caution when translating to humans. Second, pay attention to samples and contexts: results from small samples or specific populations (such as elite athletes or specific age groups) may not apply to you; studies based primarily on European and American populations also need scrutiny for applicability to Taiwanese populations. Third, emphasize effect size rather than just “statistical significance”: statistical significance does not equal a practically meaningful benefit—ask “does this difference matter in real training or health terms?” Fourth, be wary of over-extrapolation and commercialization: preliminary findings from a single study are often exaggerated into “miracle” products or methods; wait for replication and systematic reviews. Fifth, judge based on the “consistency” of mechanistic, associative, and interventional evidence, rather than rejecting everything because of one study’s flaws or accepting everything because of one impressive result. Sixth, understand that “individual variation” is the norm in sports science: the same intervention produces different responses in different people due to genetics, training background, lifestyle, and environment. Research presents group averages—when applying findings to yourself, observe your own actual responses and adjust accordingly. Seventh, prioritize the “fundamentals”: sleep, nutrition, consistent training, and recovery—these have overwhelming evidence and clear benefits—are always worth investing in before novel supplements, equipment, or methods. Many seemingly sophisticated interventions offer marginal benefits far smaller than getting the basics right. Sports science is a constantly evolving field. Maintaining an open yet critical attitude, updating your knowledge as evidence evolves, respecting individual differences, and valuing fundamentals are what allow you to truly translate cutting-edge research from international journals into training and health decisions that are useful, safe, and sustainable long-term—rather than blindly following trends or deferring to a single authority.

Key Takeaways

Synthesizing the interdisciplinary research and mechanistic analyses above, the core points can be distilled as follows: Do not worship a single gene: no “speed gene” can determine success or failure—training is the protagonist. Genetic testing as a reference, not a verdict: it can be used to understand individual recovery tendencies and training preferences. Altitude training varies by individual: monitor ferritin and hematocrit before and after going to Hehuan Mountain to assess individual responses. Reject genetic screening of children: it violates sports ethics and is scientifically untenable. Prioritize phenotypic monitoring: actual training data (power, lactate, HRV) guide daily decisions better than genes. Behind these points lies the convergence of multiple fields—sleep science, immunology, genomics, neuroscience, microbiology, endocrinology, and data science—which together convey a core message: the benefits and adaptations of exercise are the integrated result of multiple body systems working in coordination, not something captured by any single factor. Understanding this interdisciplinary perspective helps us move beyond fragmented “treat-the-symptom” thinking and view training, recovery, and health more holistically. Only by integrating these principles into daily training and life, and dynamically adjusting based on individual conditions, actual responses, and professional advice, can we translate cutting-edge findings from top international journals into practices that are truly feasible, safe, and sustainable within Taiwan’s climate, events, and lifestyle context. The value of sports science ultimately lies in helping every athlete—elite or amateur, young or old—exercise smarter, healthier, and with more enjoyment, achieving physical and mental growth along the way.

Practical Recommendations for Taiwanese Athletes

1. Do not worship a single gene: No “speed gene” can determine success or failure—training is the protagonist.
2. Genetic testing as a reference, not a verdict: It can be used to understand individual recovery tendencies and training preferences.
3. Altitude training varies by individual: Monitor ferritin and hematocrit before and after going to Hehuan Mountain to assess individual responses.
4. Reject genetic screening of children: It violates sports ethics and is scientifically untenable.
5. Prioritize phenotypic monitoring: Actual training data (power, lactate, HRV) guide daily decisions better than genes.

Research Citations and Further Reading

• Yang, N., et al. (2003). ACTN3 genotype is associated with human elite athletic performance. American Journal of Human Genetics, 73(3), 627–631.
• Montgomery, H. E., et al. (1998). Human gene for physical performance. Nature, 393, 221–222.
• Beall, C. M., et al. (2010). Natural selection on EPAS1 (HIF2α) in Tibetan highlanders. PNAS, 107(25), 11459–11464.
• Bouchard, C., et al. (2011). Genomic predictors of the maximal O2 uptake response to standardized exercise training (HERITAGE). Journal of Applied Physiology, 110(5), 1160–1170.

This article is a translation of sports science knowledge. Individual physiological responses vary. Please consult professional coaches and sports medicine physicians before making any training or intervention adjustments, and proceed gradually according to your personal health status.

Related Reading

• The Genetic Influence on Cycling Training: How ACTN3 Genotypes Predict Power and Endurance
• The Genetics of Running: How ACTN3 and ACE Genotypes Affect Running Ability
• Sports Genetics: The Impact of ACTN3 and ACE Genes on Endurance Performance
• The Significance of Sports Genetic Testing for Training: What ACTN3 and ACE Genes Tell You