Reply from Alun G. Williams and Jonathan P. Folland

Abstract

The weight of evidence suggests, and indeed it is widely accepted, that physical performance phenotypes are highly polygenic (Rankinen et al. 2006; Spurway, 2006). Based on that suggestion and using clearly defined inclusion criteria, in our recent article (Williams & Folland, 2008) we showed that human genetic potential for endurance performance depends on polymorphisms of at least 23 loci and probably many more. We then developed the first genetic algorithm for endurance performance and used this to show that it is extremely unlikely that even a single individual in the world possesses what could be termed a ‘perfect’ polygenic profile for endurance. We concluded that world records should continue to advance, although probably at a steadily reducing rate, purely through an ever-increasing pool of participants that includes individuals with genetic profiles more advantageous for endurance performance. The current letter to the editor advances the notion that ‘mental’ factors make significant contributions to success in sport. For example, mental toughness, tactical astuteness, team coherence, anticipation and decision-making, and motivation to endure pain during training and competition were suggested as key psychological traits. We would agree unreservedly. The qualities that make a champion athlete are legion and, we believe, certainly include those psychological factors suggested. We are aware of the impact that psychological factors can play in sport (Gould et al. 2002) and can have upon endurance-related phenotypes specifically (Crews, 1992). Accordingly we would encourage efforts to explore genetic influences on the psychological traits that influence endurance. Although rather outside our particular fields of expertise, we believe the first steps in identifying genetic influences on psychological traits that influence endurance performance would be to collate evidence to demonstrate that certain psychological traits are unequivocally related to improved endurance performance. In other words, a body of evidence similar to that associating maximal rate of oxygen uptake, economy of movement, lactate/ventilatory threshold and oxygen uptake kinetics (Jones & Carter, 2000) with endurance performance. To the best of our knowledge this has not yet been achieved. Next, evidence from twin or family studies would be useful to confirm and quantify the extent of the genetic (versus environmental) influences on those psychological phenotypes. In other words, evidence similar to that for the maximal rate of oxygen uptake, where heritability estimates are typically around 50% both in sedentary individuals and in terms of their response to training (Klissouras, 1971; Bouchard et al. 1986, 1998, 1999; Fagard et al. 1991). If those steps are taken successfully, researchers could then use their understanding of the underlying neurophysiology to identify candidate genes and examine their association (in cross-sectional or longitudinal studies) with critical psychological phenotypes. The demonstration of such genotype–phenotype associations would justify inclusion of those genetic loci in an updated genetic algorithm for endurance performance. An alternative and more direct approach involves identifying candidate genes for exercise and competition behaviours and investigating their association with endurance performance, irrespective of whether psychological phenotypes are or can be measured. The fact is that if any particular genetic polymorphism is associated with endurance sufficiently, regardless of mechanism, then that polymorphism should be identifiable using a ‘case-control’ study design, comparing elite athletes with non-elite controls. Six of the 23 polymorphisms included in our algorithm fell into this category, i.e. the only evidence of association with an endurance phenotype was from a case-control study with no direct evidence of the mechanism (mental or physical). Therefore, it is possible that some of the identified polymorphisms have neurophysiological and behavioural mechanisms of action, although in most cases there are good reasons for thinking the mechanism is local to skeletal muscle or the cardiovascular system. A further development of research of this kind that, initially at least, completely disregards the likely underlying physiological mechanisms, would be to conduct a genome-wide case-control study that does not have a priori hypotheses regarding particular genes. While this approach is proving fruitful in the study of genotype associations with phenotypes that are overtly related to disease (Altshuler & Daly, 2007), no equivalent study has yet been conducted with phenotypes chosen specifically because they are associated with elite athletic performance. It is probably only a matter of time before this occurs. The information that results can be incorporated into updated versions of the novel genetic algorithm for human endurance that we published recently in this journal (Williams & Folland, 2008). We are grateful to Dr Marc Jones (Staffordshire University, UK) for discussion regarding these issues.