Vassilis Klissouras

Plasticity in human motor cortex is in part genetically determined

Neuronal plasticity refers to the ability of the brain to change in response to different experiences. Plasticity varies between people, but it is not known how much of this variability is due to differences in their genes. In humans, plasticity can be probed by a protocol termed paired associative stimulation and the changes in the motor system that are brought about by such stimulation are thought to be due to strengthening synapses which connect different neurons. We examined pairs of sisters which were either genetically identical (monozygotic) or different (dizygotic). We found that the variability within the monozygotic sister pairs was less than the variability within the dizygotic sister pairs. That plasticity in human motor cortex is in a substantial part genetically determined may be relevant for motor learning and neurorehabilitation, such as after stroke.

The effect of training in male prepubertal and pubertal monozygotic twins

Nine male pairs of monozygotic twins aged 11–14xa0years, height 147 (7.6)xa0cm and body mass 39.7 (9.6)xa0kg, participated in this study. Twin zygocity was tested using morphological, dermatoglyphic and hematologic methods, and Tanners five stages were used for the evaluation of biological maturation. One twin from each pair undertook training for 6xa0months, three times a week, with running at 85–120% of the lactate anaerobic threshold (LT). Anthropometrics, determination of maximum O2 uptake (V̇O2max), LT and maximal blood lactate concentration ([La]max) was carried out before, during and after training. No significant difference existed between the trained twins and their untrained brothers before training. After training, the trained twins increased their V̇O2max (per kg body mass) by 10.6% and their LT by 18.2% (P<0.01), reaching values that differed significantly from those of their untrained brothers [57.5 (3.6)xa0ml·kg−1·min−1 vs 55.4 (3.3)xa0ml·kg−1·min−1 and 13.4 (1.1)xa0km·h−1 vs 12.7 (1.1)xa0km·h−1, respectively]. In addition, in the trained twins relative body fat was reduced (P<0.05) from 17.8 to 16.2% and their somatotype altered significantly (decrease of endomorphy and mesomorphy and increase of ectomorphy), while in the untrained twins there was no change in these parameters. Both groups of twins significantly increased their absolute V̇O2max after the 6xa0months of training, the trained by 14,9% [from 2.08 (0.43) to 2.37 (0.45)xa0l·min−1] and the untrained by 10.5% [from 2.10 (0.41) to 2.32 (0.47)xa0l·min−1], but no difference was registered between them. A comparison of the intrapair changes in V̇O2max of prepubertal and pubertal twins showed an influence of training in the prepubertal (19.3% vs 5.2%) but not in the pubertal twins (12.7% vs 13.1%). Using analysis of variance, the relative importance of training, heredity and their interaction was evaluated to be 20%, 70% and 10%, respectively, for the change in body fat, 35%, 45% and 20%, respectively, for the change in relative V̇O2max and 25–30%, 50–60% and 15–20%, respectively, for the change in LT. In conclusion, training during pubertal growth can favour aerobic power (depending on body composition) as well as aerobic capacity, but it has no effect on absolute V̇O2max. Genetic control seems to have a strong effect on the extent of adaptations, and the genotype—training interaction explains a small, but prominent part of them.

Influence of Physical Exertion on Mental Performance with Reference to Training

The aim of this study was to assess the effect of physical exertion (treadmill) on mental performance (matching a comparison design). Nine pairs of monozygotic twins (boys aged 11 to 14 yr.) were randomly divided into two groups, one trained and one untrained, while eight boys of the same age served as a control group. The trained group underwent a specifically designed program lasting six months. The trained and untrained groups performed on the treadmill for 20 min. at a running speed intensity above their individual anaerobic thresholds. Mental performance was evaluated by analysing mean number of correct answers, time taken to reach correct answers (decision time), and wrong answers. A 3 × 2 (group × pre/posttest) analysis of variance with repeated measures on the last factor yielded no significant differences; however, significant pre- versus posttest differences on correct answers and decision times occurred among the exercised groups.

Heritability in neuromuscular coordination: implications for motor control strategies.

PURPOSEnThe aim of this study was to assess the relative power of genetic and environmental contribution to the variation observed in neuromuscular coordination.nnnMETHODSnUsing the twin model and comparing intrapair differences between monozygotic (MZ) and dizygotic (DZ) twins, we derived heritability estimates (h2). Forty healthy male twins, 10 MZ and 10 DZ pairs, aged 21.5 +/- 2.4 and 21 +/- 2.1 yr, respectively, performed a series of elbow flexions in one degree of freedom with different velocities attempting to accurately reach a target. Neuromuscular coordination was evaluated for both accuracy and economy of movement and assessed by kinematics and EMG activity.nnnRESULTSnThe heritability in movement accuracy as assessed by the displacement from the target at 70% maximal velocity was 0.87. The accuracy at 30% and 50% of maximal velocity showed that the intrapair variation of MZ twins did not differ significantly from that of DZ twins. High heritability indexes of 0.85 and 0.73 were found for neuromuscular coordination as expressed by movement economy, assessed by the relative EMG activity of biceps long head at 70% and 50% of maximal velocity; no genetic dependence was found for low velocities.nnnCONCLUSIONnIn this study, heredity accounted for most of the existing differences in neuromuscular coordination in fast movements. This implies that movement strategies, which are organized in the CNS and control fast movements, are also strongly genetically dependent.

Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement.

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify childrens athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future.

Chapter Four - Genomics of Elite Sporting Performance: What little We Know and Necessary Advances

Numerous reports of genetic associations with performance- and injury-related phenotypes have been published over the past three decades; these studies have employed primarily the candidate gene approach to identify genes that associate with elite performance or with variation in performance-and/or injury-related traits. Although generally with small effect sizes and heavily prone to type I statistic error, the number of candidate genetic variants that can potentially explain elite athletic status, injury predisposition, or indeed response to training will be much higher than that examined by numerous biotechnology companies. Priority should therefore be given to applying whole genome technology to sufficiently large study cohorts of world-class athletes with adequately measured phenotypes where it is possible to increase statistical power. Some of the elite athlete cohorts described in the literature might suffice, and collectively, these cohorts could be used for replication purposes. Genome-wide association studies are ongoing in some of these cohorts (i.e., Genathlete, Russian, Spanish, Japanese, United States, and Jamaican cohorts), and preliminary findings include the identification of one single nucleotide polymorphism (SNP; among more than a million SNPs analyzed) that associates with sprint performance in Japanese, American (i.e., African American), and Jamaican cohorts with a combined effect size of ~2.6 (P-value <5×10(-7)) and good concordance with endurance performance between select cohorts. Further replications of these signals in independent cohorts will be required, and any replicated SNPs will be taken forward for fine-mapping/targeted resequencing and functional studies to uncover the underlying biological mechanisms. Only after this lengthy and costly process will the true potential of genetic testing in sport be determined.

Athlome Project Consortium: a concerted effort to discover genomic and other “omic” markers of athletic performance

Despite numerous attempts to discover genetic variants associated with elite athletic performance, injury predisposition, and elite/world-class athletic status, there has been limited progress to date. Past reliance on candidate gene studies predominantly focusing on genotyping a limited number of single nucleotide polymorphisms or the insertion/deletion variants in small, often heterogeneous cohorts (i.e., made up of athletes of quite different sport specialties) have not generated the kind of results that could offer solid opportunities to bridge the gap between basic research in exercise sciences and deliverables in biomedicine. A retrospective view of genetic association studies with complex disease traits indicates that transition to hypothesis-free genome-wide approaches will be more fruitful. In studies of complex disease, it is well recognized that the magnitude of genetic association is often smaller than initially anticipated, and, as such, large sample sizes are required to identify the gene effects robustly. A symposium was held in Athens and on the Greek island of Santorini from 14-17 May 2015 to review the main findings in exercise genetics and genomics and to explore promising trends and possibilities. The symposium also offered a forum for the development of a position stand (the Santorini Declaration). Among the participants, many were involved in ongoing collaborative studies (e.g., ELITE, GAMES, Gene SMART, GENESIS, and POWERGENE). A consensus emerged among participants that it would be advantageous to bring together all current studies and those recently launched into one new large collaborative initiative, which was subsequently named the Athlome Project Consortium.

Heritability of motor control and motor learning

The aim of this study was to elucidate the relative contribution of genes and environment on individual differences in motor control and acquisition of a force control task, in view of recent association studies showing that several candidate polymorphisms may have an effect on them. Forty‐four healthy female twins performed brisk isometric abductions with their right thumb. Force was recorded by a transducer and fed back to the subject on a computer screen. The task was to place the tracing of the peak force in a force window defined between 30% and 40% of the subjects maximum force, as determined beforehand. The initial level of proficiency was defined as the number of attempts reaching the force window criterion within the first 100 trials. The difference between the number of successful trials within the last and the first 100 trials was taken as a measure of motor learning. For motor control, defined by the initial level of proficiency, the intrapair differences in monozygotic (MZ) and dizygotic (DZ) twins were 6.8 ± 7.8 and 13.8 ± 8.4, and the intrapair correlations 0.77 and 0.39, respectively. Heritability was estimated at 0.68. Likewise for motor learning intrapair differences in the increment of the number of successful trials in MZ and DZ twins were 5.4 ± 5.2 and 12.8 ± 7, and the intrapair correlations 0.58 and 0.19. Heritability reached 0.70. The present findings suggest that heredity accounts for a major part of existing differences in motor control and motor learning, but uncertainty remains which gene polymorphisms may be responsible.

The Future of Genomic Research in Athletic Performance and Adaptation to Training

Despite numerous attempts to discover genetic variants associated with elite athletic performance, an individuals trainability and injury predisposition, there has been limited progress to date. Past reliance on candidate gene studies focusing predominantly on genotyping a limited number of genetic variants in small, often heterogeneous cohorts has not generated results of practical significance. Hypothesis-free genome-wide approaches will in the future provide more comprehensive coverage and in-depth understanding of the biology underlying sports-related traits and related genetic mechanisms. Large, collaborative projects with sound experimental designs (e.g. clearly defined phenotypes, considerations and controls for sources of variability, and necessary replications) are required to produce meaningful results, especially when a hypothesis-free approach is used. It remains to be determined whether the novel approaches under current implementation will result in findings with real practical significance. This review will briefly summarize current and future directions in exercise genetics and genomics.

The Registry of Italian Twin Athletes (RITA): Background, design, and procedures,and twin data analysis on sport participation—An application to twin swimmers

Aiming to contribute to a better understanding of the nature and characteristics of sport participation and of the factors underlying human performance and adaptation to physical exercise, this study involved (a) the establishment of a specialized twin registry, (b) a questionnaire study, and (c) testing sessions of top level athletes. The general design and procedures of the project are described. A Registry of Italian Twin Athletes (RITA) was developed through a collaborative effort involving 25 sports federations of the Italian National Olympic Committee (CONI). Out of a total of over 1,500,000 registered athletes, some 5,000 pairs of twins practicing sports such as track and field, swimming, tennis, fencing, and cycling, were tentatively identified. A basic questionnaire was devised to address general aspects as well as specific items related to the respondents respective discipline, and a specific questionnaire was developed for each sport. As a basis for future studies, an application was conducted on the twins registered with the Swimming Federation. The data collected from the completed questionnaires of about 200 twin swimmers indicated a strong zygosity and sex effect on sport selection, with higher prevalence values for identical pairs and for males. The twins appeared to be taller than their counterparts in the general population, as appears to be true for swimmers in general. Both for anthropometry and basic swimming performance analysis, no zygosity effects were found, individual differences being presumably minimized by basic athletic selection factors. For possible genetic effects to be detected, specific and direct testing sessions on high-level performers should be undertaken.