Response to “Athletes Genotyping: Ethical and Legal Issues”

Even though the paper by An et al. did not provide any evidence to the effect that there are genetic influences on athletic performance [[1]], it has been known for more than 20 years that genetic differences play a role in human performance [[2]]. This topic was even addressed in a book entirely devoted to the evidence accumulated on this topic [[3]]. More recently the HERITAGE Family Study has demonstrated that the genetic effects on cardiorespiratory performance were visible not only in the sedentary state [[4]], but also in the ability to respond to training [[5]]. Another group of authors point out that a common polymorphism in the alpha-actinin-3 gene could play a role in muscle power [[7]]. However, we need to have several other studies on this gene before its true significance in muscle performance can be evaluated. Other genes have also generated excitement in the past based on the results of an initial study which were not or were only weakly replicated subsequently. In this regard, the latest version of the Human Fitness and Performance Gene Map strongly suggests that one needs to distinguish between several classes of performance phenotypes and that they are all likely to be influenced by large numbers of genes [[6]].

Despite these reservations regarding the framing of the problem, we agree that caution is warranted to prevent misuse of genetic data. This issue is the subject of intense debate in the industrialized world, but more in the context of human disease and public health, motivated by progress in the discovery of genes influencing predisposition to various diseases or unfavorable risk factor profiles. The prominent issues are personal enhancement, employment discrimination, privacy and insurability (primarily access to health care in the United States).

While the scientific and medical community is strongly in favor of using the power of genetic information and molecular and stem cell biology to correct an inherited disorder (gene therapy), there is strong opposition to using these technologies for the purpose of enhancement of a trait in healthy individuals. This undoubtedly reflects the concerns of the scientific community about the need to protect the individual's rights and privacy, but also to ensure that research in genetics can productively proceed with the goal of developing improved therapies and medical strategies. These issues have been addressed in some detail with a focus on fitness and performance phenotypes in an earlier publication [[3]].

In addition to the ethical concern, the utility of genetic testing for predicting an individual's phenotype is often limited, particularly for complex traits (such as coronary heart disease, depression, human performance, among many others). The reasons for this are several-fold. First, complex traits are influenced by several genes, environmental factors, and their interactions. In this context, the effect of any one gene is likely to be relatively small and will not account for a large proportion of the trait variability. In contrast, those who propose to incorporate genetic testing in programs designed to identify youth thought to be talented for sports typically make the assumption that there are genes with large effects on physical performance and trainability. Second, the magnitude of effect of a particular gene or variant is estimated for a population, not for an individual. Thus, we generally have an idea of the average effect of the variant or genotype, but that does not predict what can be expected in any given individual. Third, even if study protocols call for measuring certain aspects of the environment presumed to be relevant, there may be as yet unknown important environmental influences. Fourth, it is virtually impossible to measure such attributes as determination to succeed, technique, and tactics, which conceivably could overwhelm the nominal effect of an associated genotype. Thus, without knowledge of all relevant genotypes, environmental factors, and their interactions, knowledge of a single genotype has a poor predictive power for complex traits such as physical performance.

If knowledge of genotype does not help us to predict phenotypic outcome appreciably, then why are we engaged in this endeavor? The most important reason is that identification of relevant genes and sequence variations helps elucidate the biology of important pathways relevant to fitness and physical performance. Such research deepens our understanding of the biological and behavioral basis of interindividual differences in healthy individuals, and has implications for the prevention of common diseases.

References

• 1 An P, Borecki I B, Rankinen T, Pérusse L, Leon A S, Skinner J S, Wilmore J H, Bouchard C, Rao D C. Evidence of major genes for exercise heart rate and blood pressure at baseline and in response to 20 weeks of endurance training: The HERITAGE Family Study.  Int J Sports Med. 2003;  24 492-498
• 2 Bouchard C, Malina R M. Genetics of physiological fitness and motor performance.  Exerc Sport Sci Rev. 1986;  11 306-339
• 3 Bouchard C, Malina R M, Pérusse L. Genetics of Fitness and Physical Performance. Champaign, IL; Human Kinetics Publisher 1997: 400
• 4 Bouchard C, Daw E W, Rice T, Pérusse L, Gagnon J, Province M A, Leon A S, Rao D C, Skinner J S, Wilmore J H. Familial resemblance for VO₂max in the sedentary state: The HERITAGE Family Study.  Med Sci Sports Exerc. 1998;  30 252-258
• 5 Bouchard C, An P, Rice T, Skinner J S, Wilmore J H, Gagnon J, Pérusse L, Leon A S, Rao D C. Familial aggregation of VO₂max response to exercise training: Results from the HERITAGE Family Study.  J Appl Physiol. 1999;  87 1003-1008
• 6 Pérusse L, Rankinen T, Rauramaa R, Rivera M B, Wolfarth B, Bouchard C. The human gene map for performance and health-related fitness phenotypes: the 2002 update.  Med Sci Sports Exerc. 2003;  35 1248-1264
• 7 Yang N, MacArthur D G, Gulbin J P, Hahn A G, Beggs A H, Easteal S, North K. ACTN3 genotype is associated with human elite athletic performance.  Am J Hum Genet. 2003;  73 627-631