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

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes

Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50–85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case–control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene–environment interactions—in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically “extreme” population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully

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

Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain: Systematic review and meta-analysis

AbstractObjective To investigate the efficacy, acceptability, and safety of muscle relaxants for low back pain. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and WHO ICTRP from inception to 23 February 2021. Eligibility criteria for study selection Randomised controlled trials of muscle relaxants compared with placebo, usual care, waiting list, or no treatment in adults (≥18 years) reporting non-specific low back pain. Data extraction and synthesis Two reviewers independently identified studies, extracted data, and assessed the risk of bias and certainty of the evidence using the Cochrane risk-of-bias tool and Grading of Recommendations, Assessment, Development and Evaluations, respectively. Random effects meta-analytical models through restricted maximum likelihood estimation were used to estimate pooled effects and corresponding 95% confidence intervals. Outcomes included pain intensity (measured on a 0-100 point scale), disability (0-100 point scale), acceptability (discontinuation of the drug for any reason during treatment), and safety (adverse events, serious adverse events, and number of participants who withdrew from the trial because of an adverse event). Results 49 trials were included in the review, of which 31, sampling 6505 participants, were quantitatively analysed. For acute low back pain, very low certainty evidence showed that at two weeks or less non-benzodiazepine antispasmodics were associated with a reduction in pain intensity compared with control (mean difference -7.7, 95% confidence interval-12.1 to-3.3) but not a reduction in disability (-3.3, -7.3 to 0.7). Low and very low certainty evidence showed that non-benzodiazepine antispasmodics might increase the risk of an adverse event (relative risk 1.6, 1.2 to 2.0) and might have little to no effect on acceptability (0.8, 0.6 to 1.1) compared with control for acute low back pain, respectively. The number of trials investigating other muscle relaxants and different durations of low back pain were small and the certainty of evidence was reduced because most trials were at high risk of bias. Conclusions Considerable uncertainty exists about the clinical efficacy and safety of muscle relaxants. Very low and low certainty evidence shows that non-benzodiazepine antispasmodics might provide small but not clinically important reductions in pain intensity at or before two weeks and might increase the risk of an adverse event in acute low back pain, respectively. Large, high quality, placebo controlled trials are urgently needed to resolve uncertainty. Systematic review registration PROSPERO CRD42019126820 and Open Science Framework https://osf.io/mu2f5/

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

The HIF1A gene Pro582Ser polymorphism in Russian strength athletes

Hypoxiainducible factor-1a (encoded by HIF1A gene) controls a number of genes that are implicated in various cellular functions including glycolysis and cell proliferation and differentiation. The rs11549465 C > T polymorphism in the HIF1A gene, which produces the amino acid substitution Pro582Ser, increases protein stability and transcriptional activity and, therefore, improves glucose metabolism. The aim of our study was to investigate the association between the HIF1A Pro582Ser polymorphism and elite strength athlete status. A total of 208 Russian strength athletes (122 weightlifters and 86 wrestlers) of regional or national competitive standard and 1,413 controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. We found that the frequency of the HIF1A 582Ser variant was significantly higher in weightlifters (13.1%, p = 0.0031) and wrestlers (15.7%, p = 0.0002) compared with the controls (7.5%). Additionally, the highest (21.1%, p = 0.0052) frequency of the 582Ser variant was found in a group of elite strength athletes. Thus, our study provides evidence for an association between the HIF1A gene Pro582Ser polymorphism and elite strength athlete status. Although more replication studies are needed, the preliminary data suggest an opportunity to use the analysis of HIF1A polymorphism along with other gene variations and standard phenotypic assessment in sports selection

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

Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1) the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with adiposity indicators; and (2) the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA), and sleep duration was parental reported. Adiposity indicators included waist circumference (WC) and body mass index (BMI) z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285), sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614), LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902), or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288) relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first to use compositional analyses when examining associations of co-dependent sleep duration, sedentary time, and physical activity behaviours with adiposity indicators in preschool-aged children. The overall composition of movement behaviours appears important for healthy BMI z-scores in preschool-aged children. Future research is needed to determine the optimal movement behaviour composition that should be promoted in this age group

No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes

Background: Studies investigating associations between ACTN3 R577X and ACE I/D genotypes and endurance athletic status have been limited by small sample sizes from mixed sport disciplines and lack quantitative measures of performance. Aim: To examine the association between ACTN3 R577X and ACE I/D genotypes and best personal running times in a large homogeneous cohort of endurance runners. Methods: We collected a total of 1064 personal best 1500, 3000, 5000 m and marathon running times of 698 male and female Caucasian endurance athletes from six countries (Australia, Greece, Italy, Poland, Russia and UK). Athletes were genotyped for ACTN3 R577X and ACE ID variants. Results: There was no association between ACTN3 R577X or ACE I/D genotype and running performance at any distance in men or women. Mean (SD) marathon times (in s) were for men: ACTN3 RR 9149 (593), RX 9221 (582), XX 9129 (582) p = 0.94; ACE DD 9182 (665), ID 9214 (549), II 9155 (492) p = 0.85; for women: ACTN3 RR 10796 (818), RX 10667 (695), XX 10675 (553) p = 0.36; ACE DD 10604 (561), ID 10766 (740), II 10771 (708) p = 0.21. Furthermore, there were no associations between these variants and running time for any distance in a sub-analysis of athletes with personal records within 20% of world records. Conclusions: Thus, consistent with most case-control studies, this multi-cohort quantitative analysis demonstrates it is unlikely that ACTN3 XX genotype provides an advantage in competitive endurance running performance. For ACE II genotype, some prior studies show an association but others do not. Our data indicate it is also unlikely that ACE II genotype provides an advantage in endurance running