Genomics as a practical tool in sport - have we reached the starting line?

The genetic component of athletic performance approximates 50%, depending on which specific element of performance is considered. Limited genetic testing is already available commercially and genetic tests are likely to become powerful tools to improve sport performance in the future. Currently, however, selection of athletes for training squads or competition based on genomic data is premature. Larger volumes of longitudinal data within individual sports are needed to determine the efficacy of using genomic data in the management of elite athletes via manipulation of training load and diet based on personal genomic information

Genomics as a practical tool in sport - have we reached the starting line?

The genetic component of athletic performance approximates 50%, depending on which specific element of performance is considered. Limited genetic testing is already available commercially and genetic tests are likely to become powerful tools to improve sport performance in the future. Currently, however, selection of athletes for training squads or competition based on genomic data is premature. Larger volumes of longitudinal data within individual sports are needed to determine the efficacy of using genomic data in the management of elite athletes via manipulation of training load and diet based on personal genomic information

Titin genotype is associated with skeletal muscle fascicle length in recreationally active men and running performance in habitually trained marathon runners

Objectives The titin gene (TTN) encodes the largest described protein to date and, due to its size, provides a molecular blueprint for the organisation and assembly of the muscle sarcomere. Differences in sarcomere length, due to the expression of different titin isoforms, have been observed previously and may influence muscle fascicle length, which could provide an advantage for running performance. Thus, the aim of this study was to investigate if the TTN rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men and marathon personal best time in elite male marathon runners, and to investigate any differences in genotype frequency between RA and MR.Methods The sample comprised 278 healthy, unrelated Caucasian men who all gave written consent to take part. Participants were categorised as either recreationally active [RA; n = 137; age = 20.7 (2.7) yr; height = 1.79 (0.06) m; mass = 75.3 (10.1) kg] or marathon runners [MR; n = 141; age = 34.9 (7.8) yr; height = 1.79 (0.07) m; mass = 66.5 (6.7) kg]. MR comprised Olympic, international and national level athletes, who had all achieved marathon personal best times under 2 hr 36 mins. Resting fascicle length of the vastus lateralis muscle was assessed in vivo using B-mode ultrasonography at 50% of muscle length in RA only. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated and genotyped using real-time polymerase chain reaction. Independent samples t-tests were used to determine any genotype-dependent differences in fascicle length in RA and marathon personal best time in MR. Pearson’s chi-square tests were conducted to compare genotype frequencies between RA and MR.Results Vastus lateralis fascicle length was 10.4% longer in CC homozygotes than CT heterozygotes (P = 0.003) in RA. In the absence of any TT homozygotes, reflective of the low T-allele frequency within Caucasian populations, it is unclear if fascicle length for this group would have been smaller still. No differences in genotype frequency between the RA and MR groups were observed (P = 0.500), however, within the MR group the T-allele carriers demonstrated marathon personal best times 2 min 25 s faster than CC homozygotes (P = 0.020).Conclusions These results suggest that the T-allele at rs10497520 in the TTN gene is associated with shorter skeletal muscle fascicle length and conveys an advantage for marathon running performance in habitually trained men

No association between tendon-related genes and performance in elite European Caucasian marathon runners.

Tendons adapt to load under normal physiological conditions, however, under extreme loading conditions, such as those experienced by elite endurance athletes, incomplete adaptation may occur and cause injury. The prevalence of tendinopathies in elite endurance athletes is approximately 50%, thus variability exists in an athlete's tolerance to extreme loading. A number of intrinsic and extrinsic factors contribute to modulating injury risk, some of which are modifiable and others, such as genetic variants, are non-modifiable. It was hypothesized that elite marathon runners would possess a genotype associated with enhanced tendon function, and thus protective against tendinopathy. Here, we compared the genotype frequencies of six genetic variants (COL1A1 rs1800012, VEGFA rs699947, TIMP2 rs4789932, MMP3 rs591058, MMP3 rs650108, MMP3 rs679620), previously associated with tendinopathy, in elite (men <2 h 30 min, n = 109, women <3 h 00 min, n = 99) and sub-elite (men 2 h 30 min-2 h 45 min, n = 189; women 3 h 00 min-3 h 15 min, n = 71) marathon runners with those of a non-athletic control group (n = 564). Genotype associations with marathon personal best time in the athlete group were also investigated. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated, and genotyped for all six variants using real-time PCR. Genotype frequency differed between athletes and controls for TIMP2 rs4789932 (TT = 17%, CT = 51%, CC = 32% vs. TT = 22%, CT = 42%, CC = 36%, respectively; χ2 = 8.135, P = 0.017) only. However, there was no clear difference in allele frequencies between groups for TIMP2 rs4789932. MMP3 rs650108 genotype frequency differed between female elite and sub-elite athletes (χ2 = 11.913, P = 0.003) only and, as hypothesized, it was the “risk” A-allele that was ~10% less frequent in the elite, than sub-elite athletes. Following combination of all genotype data into a total genotype score, no differences in score between athletes and controls were observed (t = 2.93, P = 0.769). Similarly, no associations between total genotype score and marathon personal best time in male and female runners were observed (r ≤ 0.066, P ≥ 0.394). The results suggest elite marathon runners do not possess a genotype protective against tendinopathy, at least for the tendon-related genetic variants we investigated

TTN genotype is associated with fascicle length and marathon running performance.

Titin provides a molecular blueprint for muscle sarcomere assembly and sarcomere length can vary according to titin isoform expression. If variations in sarcomere length influence muscle fascicle length, this may provide an advantage for running performance. Thus the aim of this study was to investigate if the titin (TTN) rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men (RA; n = 137) and marathon personal best time in male marathon runners (MR; n = 141). Fascicle length of the vastus lateralis was assessed in vivo using B-mode ultrasonography at 50% of muscle length in RA. All participants provided either a whole blood, saliva or buccal cell sample, from which DNA was isolated and genotyped using real-time polymerase chain reaction. Vastus lateralis fascicle length was 10.4% longer in CC homozygotes, those carrying two copies of the C-allele, than CT heterozygotes (p = 0.003) in RA. In the absence of any TT homozygotes, reflective of the low T-allele frequency within Caucasian populations, it is unclear if fascicle length for this group would have been smaller still. No differences in genotype frequency between the RA and MR groups were observed (p = 0.500), although within the MR group the T-allele carriers demonstrated marathon personal best times 2 min 25 s faster than CC homozygotes (p = 0.020). These results suggest that the T-allele at rs10497520 in the TTN gene is associated with shorter skeletal muscle fascicle length and conveys an advantage for marathon running performance in habitually trained men. This article is protected by copyright. All rights reserved

Bone mineral density in high-level endurance runners: part B—genotype-dependent characteristics

Purpose: Inter-individual variability in bone mineral density (BMD) exists within and between endurance runners and non-athletes, probably in part due to differing genetic profiles. Certainty is lacking, however, regarding which genetic variants may contribute to BMD in endurance runners and if specific genotypes are sensitive to environmental factors, such as mechanical loading via training. Method: Ten single-nucleotide polymorphisms (SNPs) were identified from previous genome-wide and/or candidate gene association studies that have a functional effect on bone physiology. The aims of this study were to investigate (1) associations between genotype at those 10 SNPs and bone phenotypes in high-level endurance runners, and (2) interactions between genotype and athlete status on bone phenotypes. Results: Female runners with P2RX7 rs3751143 AA genotype had 4% higher total-body BMD and 5% higher leg BMD than AC + CC genotypes. Male runners with WNT16 rs3801387 AA genotype had 14% lower lumbar spine BMD than AA genotype non-athletes, whilst AG + GG genotype runners also had 5% higher leg BMD than AG + GG genotype non-athletes. Conclusion: We report novel associations between P2RX7 rs3751143 genotype and BMD in female runners, whilst differences in BMD between male runners and non-athletes with the same WNT16 rs3801387 genotype existed, highlighting a potential genetic interaction with factors common in endurance runners, such as high levels of mechanical loading. These findings contribute to our knowledge of the genetic associations with BMD and improve our understanding of why some runners have lower BMD than others

Associations of bone mineral density-related genes and marathon performance in elite European Caucasian marathon runners.

Bone mineral density (BMD) is a multi-factorial phenotype determined by factors such as physical activity, diet and a sizeable genetic component. Athletic populations tend to possess higher BMD than non-athletes due to a larger volume of exercise completed. Despite this, some endurance runners can possess low BMD and/or suffer stress fractures, which can have negative impacts on their health and performance. Therefore, we hypothesised that elite endurance runners would possess a genotype associated with enhanced BMD and a reduced risk of injury, resulting in less training interruption and greater potential success. The study compared the genotype and allele frequencies of 5 genetic variants associated with BMD (LRP5 rs3736228, TNFRSF11B rs4355801, VDR rs2228570, WNT16 rs3801387, AXIN1 rs9921222) in elite (men < 2 h 30 min, n = 110; women < 3 h 00 min, n = 98) and sub-elite (men 2 h 30 min – 2 h 45 min, n = 181; women 3 h 00 min – 3 h 15 min, n = 67) marathon runners with those of a non-athlete control population (n = 474). We also investigated whether marathon personal best time was associated with a more “advantageous” BMD genotype. Congruent with our hypothesis, the “risk” T allele for the AXIN1 rs9921222 polymorphism was 5% more frequent in the control group than in sub-elites (P = 0.030, χ2 = 4.69) but no further differences were observed for this variant (P ≥ 0.083, χ2 ≤ 4.98). WNT16 rs3801387 genotype frequency differed between athletes and controls (P = 0.002, χ2 = 12.02) and elites vs controls (P = 0.008, χ2 = 9.72), as did allele frequency. However, contrary to our hypothesis, it was the “risk” A allele that was ~5% more frequent in athletes than controls. Similarly, when combining data from all 5 variants, the athletes had a lower Total Genotype Score than controls (53.6 vs 65.7; P ≤ 0.001), again suggesting greater genetic susceptibility to bone injury in athletes. Personal best times were not associated with genotype in any comparison. These results suggest that high-level endurance runners do not benefit from genetic resistance to bone injury and a resulting ability to sustain large training volumes, contradicting our hypothesis. High-level endurance runners appear to be at a higher risk of bone injury from a genetic perspective, for as yet unexplained reasons, although large inter-individual differences in genetic risk exist

Genetic Polymorphisms Related to VO2max Adaptation Are Associated With Elite Rugby Union Status and Competitive Marathon Performance

PURPOSE: Genetic polymorphisms have been associated with the adaptation to training in maximal oxygen uptake (V˙O2max). However, the genotype distribution of selected polymorphisms in athletic cohorts is unknown, with their influence on performance characteristics also undetermined. This study investigated whether the genotype distributions of 3 polymorphisms previously associated with V˙O2max training adaptation are associated with elite athlete status and performance characteristics in runners and rugby athletes, competitors for whom aerobic metabolism is important. METHODS: Genomic DNA was collected from 732 men including 165 long-distance runners, 212 elite rugby union athletes, and 355 nonathletes. Genotype and allele frequencies of PRDM1 rs10499043 C/T, GRIN3A rs1535628 G/A, and KCNH8 rs4973706 T/C were compared between athletes and nonathletes. Personal-best marathon times in runners, as well as in-game performance variables and playing position, of rugby athletes were analyzed according to genotype. RESULTS: Runners with PRDM1 T alleles recorded marathon times ∼3 minutes faster than CC homozygotes (02:27:55 [00:07:32] h vs 02:31:03 [00:08:24] h, P = .023). Rugby athletes had 1.57 times greater odds of possessing the KCNH8 TT genotype than nonathletes (65.5% vs 54.7%, χ2 = 6.494, P = .013). No other associations were identified. CONCLUSIONS: This study is the first to demonstrate that polymorphisms previously associated with V˙O2max training adaptations in nonathletes are also associated with marathon performance (PRDM1) and elite rugby union status (KCNH8). The genotypes and alleles previously associated with superior endurance-training adaptation appear to be advantageous in long-distance running and achieving elite status in rugby union

Are isomeric alkenes used in species recognition among neo-tropical stingless bees (Melipona spp)

The majority of our understanding of the role of cuticular hydrocarbons (CHC) in recognition is based largely on temperate ant species and honey bees. The stingless bees remain relatively poorly studied, despite being the largest group of eusocial bees, comprising more than 400 species in some 60 genera. The Meliponini and Apini diverged between 80-130 Myr B.P. so the evolutionary trajectories that shaped the chemical communication systems in ants, honeybees and stingless bees may be very different. Therefore, the main aim of this study was to study if a unique species CHC signal existed in Neotropical stingless bees, as shown for many temperate species, and if so what compounds are involved. This was achieved by collecting CHC data from 24 colonies belonging to six species of Melipona from North-eastern Brazil and comparing this new data with all previously published CHC studies on Melipona. We found that each of the eleven Melipona species studied so far each produced a unique species CHC signal based around their alkene isomer production. A remarkable number of alkene isomers, up to 25 in M. asilvai, indicated the diversification of alkene positional isomers among the stingless bees. The only other group to have really diversified in alkene isomer production are the primitively eusocial Bumblebees (Bombus spp), which are the sister group of the stingless bees. Furthermore, among the eleven Neotropical Melipona species we could detect no effect of the environment on the proportion of alkane production as has been suggested for some other species