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Competing Interests: Declaration of interest statement All authors declare no competing interests.

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male-born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case-by-case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision-making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

The aim of this review was to critically appraise the literature concerning the genetic association with athlete status, physical performance, and injury risk in soccer. The objectives were to provide guidance on which genetic markers could potentially be used as part of future practice in soccer and to provide direction for future research in this area. The most compelling evidence identified six genetic polymorphisms to be associated with soccer athlete status ( ACE I/D; ACTN3 rs1815739; AGT rs699; MCT1 rs1049434; NOS3 rs2070744; PPARA rs4253778), six with physical performance ( ACTN3 rs1815739; AMPD1 rs17602729; BDNF rs6265; COL2A1 rs2070739; COL5A1 rs12722; NOS3 rs2070744), and seven with injury risk ( ACTN3 rs1815739; CCL2 rs2857656; COL1A1 rs1800012; COL5A1 rs12722; EMILIN1 rs2289360; IL6 rs1800795; MMP3 rs679620). As well as replication by independent groups, large-scale genome-wide association studies are required to identify new genetic markers. Future research should also investigate the physiological mechanisms associating these polymorphisms with specific phenotypes. Further, researchers should investigate the above associations in female and non-Caucasian soccer players, as almost all published studies have recruited male participants of European ancestry. Only after robust, independently replicated genetic data have been generated, can genetic testing be considered an additional tool to potentially inform future practice in soccer., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes., Design: A case-control genetic association study., Setting: Institutional (university)., Participants: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men)., Interventions: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes., Main Outcome Measure: Elite athlete status with groups compared using χ 2 and odds ratio (OR)., Results: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P < 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status., Conclusions: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Part 1 of this genetic association series highlighted several genetic variants independently associated with elite status in rugby. However, it is highly likely that the genetic influence on elite status is polygenic due to the interaction of multiple genes. Therefore, the aim of the present study was to investigate whether polygenic profiles of elite rugby athletes differed from non-athletes utilising 13 genetic polymorphisms previously associated with tendon/ligament injury. Total genotype score (TGS) was calculated and multifactor dimensionality reduction (MDR) was used to calculate SNP-SNP epistasis interactions. Based on our elite rugby data from Part 1, mean TGS was significantly higher in elite rugby athletes (52.1 ± 10.7) than non-athletes (48.7 ± 10.8). There were more elite rugby athletes (54%) within the upper TGS quartile, and fewer (46%) within the lower quartile, compared to non-athletes (31% and 69%, respectively; P  = 5·10 -5 ), and the TGS was able to distinguish between elite rugby athletes and non-athletes (area under the curve = 0.59; 95% confidence interval 0.55-0.63; P  = 9·10 -7 ). Furthermore, MDR identified a three-SNP model of COL5A1 rs12722, COL5A1 rs3196378 and MIR608 rs4919510 that was best able to predict elite athlete status, with a greater frequency of the CC-CC-CC genotype combination in elite rugby athletes (9.8%) than non-athletes (5.3%). We propose that elite rugby athletes possess "preferable" musculoskeletal soft-tissue injury-associated polygenic profiles that have helped them achieve success in the high injury risk environment of rugby. These data may, in future, have implications for the individual management of musculoskeletal soft-tissue injury. Highlights Elite rugby athletes have preferable polygenic profiles to non-athletes in terms of genetic variants previously associated with musculoskeletal soft-tissue injury.The total genotype score was able to distinguish between elite rugby athletes and non-athletes. COL5A1 rs12722, COL5A1 rs3196378 and MIR608 rs4919510 produced the best model for predicting elite athlete status.We propose that elite rugby athletes may have an inherited advantage to achieving elite status due to an increased resistance to soft-tissue injury.

There is growing evidence of genetic contributions to tendon and ligament pathologies. Given the high incidence and severity of tendon and ligament injuries in elite rugby, we studied whether 13 gene polymorphisms previously associated with tendon/ligament injury were associated with elite athlete status. Participants from the RugbyGene project were 663 elite Caucasian male rugby athletes (RA) (mean (standard deviation) height 1.85 (0.07) m, mass 101 (12) kg, age 29 (7) yr), including 558 rugby union athletes (RU) and 105 rugby league athletes. Non-athletes (NA) were 909 Caucasian men and women (56% female; height 1.70 (0.10) m, mass 72 (13) kg, age 41 (23) yr). Genotypes were determined using TaqMan probes and groups compared using Χ 2 and odds ratio (OR). COLGALT1 rs8090 AA genotype was more frequent in RA (27%) than NA (23%; P  = 0.006). COL3A1 rs1800255 A allele was more frequent in RA (26%) than NA (23%) due to a greater frequency of GA genotype (39% vs 33%). For MIR608 rs4919510, RA had 1.7 times the odds of carrying the CC genotype compared to NA. MMP3 rs591058 TT genotype was less common in RA (25.1%) than NA (31.2%; P  < 0.04). For NID1 rs4660148, RA had 1.6 times the odds of carrying the TT genotype compared to NA. It appears that elite rugby athletes have an inherited advantage that contributes to their elite status, possibly via resistance to soft tissue injury. These data may, in future, assist personalised management of injury risk amongst athletes. Highlights The elite rugby athletes we studied had differing genetic characteristics to non-athletes regarding genetic variants previously associated with soft-tissue injury risk. COLGALT1 rs8090, COL3A1 rs1800255, MIR608 rs4919510, MMP3 rs591058 and NID1 rs4660148 were all associated with elite status in rugby.We propose that elite rugby athletes might possess an inherited resistance to soft tissue injury, which has enabled them to achieve elite status despite exposure to the high-risk environment of elite rugby.

Abstract: Dines, HR, Nixon, J, Lockey, SJ, Herbert, AJ, Kipps, C, Pedlar, CR, Day, SH, Heffernan, SM, Antrobus, MR, Brazier, J, Erskine, RM, Stebbings, GK, Hall, ECR, and Williams, AG. Collagen gene polymorphisms previously associated with resistance to soft-tissue injury are more common in competitive runners than nonathletes. J Strength Cond Res 37(4): 799-805, 2023-Single-nucleotide polymorphisms (SNPs) of collagen genes have been associated with soft-tissue injury and running performance. However, their combined contribution to running performance is unknown. We investigated the association of 2 collagen gene SNPs with athlete status and performance in 1,429 Caucasian subjects, including 597 competitive runners (354 men and 243 women) and 832 nonathletes (490 men and 342 women). Genotyping for COL1A1 rs1800012 (C > A) and COL5A1 rs12722 (C > T) SNPs was performed by a real-time polymerase chain reaction. The numbers of "injury-resistant" alleles from each SNP, based on previous literature (rs1800012 A allele and rs12722 C allele), were combined as an injury-resistance score (RScore, 0-4; higher scores indicate injury resistance). Genotype frequencies, individually and combined as an RScore, were compared between cohorts and investigated for associations with performance using official race times. Runners had 1.34 times greater odds of being rs12722 CC homozygotes than nonathletes (19.7% vs. 15.5%, p = 0.020) with no difference in the rs1800012 genotype distribution ( p = 0.659). Fewer runners had an RScore 0 of (18.5% vs. 24.7%) and more had an RScore of 4 (0.6% vs. 0.3%) than nonathletes ( p < 0.001). Competitive performance was not associated with the COL1A1 genotype ( p = 0.933), COL5A1 genotype ( p = 0.613), or RScore ( p = 0.477). Although not associated directly with running performance among competitive runners, a higher combined frequency of injury-resistant COL1A1 rs1800012 A and COL5A1 rs12722 C alleles in competitive runners than nonathletes suggests these SNPs may be advantageous through a mechanism that supports, but does not directly enhance, running performance., (Copyright © 2022 National Strength and Conditioning Association.)

Success in long-distance running relies on multiple factors including oxygen utilisation and lactate metabolism, and genetic associations with athlete status suggest elite competitors are heritably predisposed to superior performance. The Gly allele of the PPARGC1A Gly482Ser rs8192678 polymorphism has been associated with endurance athlete status and favourable aerobic training adaptations. However, the association of this polymorphism with performance amongst long-distance runners remains unclear. Accordingly, this study investigated whether rs8192678 was associated with elite status and competitive performance of long-distance runners. Genomic DNA from 656 Caucasian participants including 288 long-distance runners (201 men, 87 women) and 368 non-athletes (285 men, 83 women) was analysed. Medians of the 10 best UK times (Top10) for 10 km, half-marathon and marathon races were calculated, with all included athletes having personal best (PB) performances within 20% of Top10 (this study's definition of "elite"). Genotype and allele frequencies were compared between athletes and non-athletes, and athlete PB compared between genotypes. There were no differences in genotype frequency between athletes and non-athletes, but athlete Ser allele carriers were 2.5% faster than Gly/Gly homozygotes ( p  = 0.030). This study demonstrates that performance differences between elite long-distance runners are associated with rs8192678 genotype, with the Ser allele appearing to enhance performance.

Abstract: Moreland, E, Borisov, OV, Semenova, EA, Larin, AK, Andryushchenko, ON, Andryushchenko, LB, Generozov, EV, Williams, AG, and Ahmetov, II. Polygenic profile of elite strength athletes. J Strength Cond Res 36(9): 2509-2514, 2022-Strength is a heritable trait with unknown polygenic nature. So far, more than 200 DNA polymorphisms associated with strength/power phenotypes have been identified majorly involving nonathletic populations. The aim of the present study was to investigate individually and in combination the association of 217 DNA polymorphisms previously identified as markers for strength/power phenotypes with elite strength athlete status. A case-control study involved 83 Russian professional strength athletes (53 weightlifters, 30 powerlifters), 209 Russian and 503 European controls. Genotyping was conducted using micro-array analysis. Twenty-eight DNA polymorphisms (located near or in ABHD17C , ACTG1 , ADCY3 , ADPGK , ANGPT2 , ARPP21 , BCDIN3D , CRTAC1 , DHODH , GBE1 , IGF1 , IL6 , ITPR1 , KIF1B , LRPPRC , MMS22L , MTHFR , NPIPB6 , PHACTR1 , PLEKHB1 , PPARG , PPARGC1A , R3HDM1 , RASGRF1 , RMC1 , SLC39A8 , TFAP2D , ZKSCAN5 genes) were identified to have an association with strength athlete status. Next, to assess the combined impact of all 28 DNA polymorphisms, all athletes were classified according to the number of "strength" alleles they possessed. All highly elite strength athletes were carriers of at least 22 (up to 34) "strength" alleles, whereas 27.8% of Russian controls had less than 22 "strength" alleles ( p < 0.0001). The proportion of subjects with a high (≥26) number of "strength" alleles was significantly greater in highly elite strength athletes (84.8%) compared with less successful strength athletes (64.9%; odd ratio [OR] = 3.0, p = 0.042), Russian (26.3%; OR = 15.6, p < 0.0001) or European (37.8%; OR = 6.4, p < 0.0001) controls. This is the first study to demonstrate that the likelihood of becoming an elite strength athlete depends on the carriage of a high number of strength-related alleles., (Copyright © 2020 National Strength and Conditioning Association.)

Context: Whether playing position influences injury in male academy soccer players (ASPs) is unclear., Objective: To determine if playing position was associated with injury in ASPs., Design: Descriptive epidemiology study., Setting: English, Spanish, Uruguayan, and Brazilian soccer academies., Patients or Other Participants: A total of 369 ASPs from the under-14 to under-23 age groups, classified as post-peak height velocity using maturity offset, and grouped as goalkeepers, lateral defenders, central defenders, lateral midfielders, central midfielders, or forwards., Main Outcome Measure(s): Injuries were recorded prospectively over 1 season. Injury prevalence proportion (IPP), days missed, and injury incidence rate (IIR, injuries/1000 training or match hours, n = 116) were analyzed according to playing position., Results: No association with playing position was observed for any injury type or location regarding IPP (P ≥ .089) or days missed (P ≥ .235). The IIR was higher in central defenders than in lateral defenders for general (9.30 versus 4.18 injuries/1000 h, P = .009), soft tissue (5.14 versus 1.95 injuries/1000 h, P = .026), and ligament or tendon injuries (2.69 versus 0.56 injuries/1000 h, P = .040). The central versus lateral or forward positions were not associated with IPP (P ≥ .051) or days missed (P ≥ .083), but general IIR was greater in the central position than the lateral or forward positions (8.67 versus 6.12 injuries/1000 h, P = .047)., Conclusions: Academy soccer players' playing positions were not associated with IPP or days missed, but the higher general, soft tissue, and ligament or tendon IIRs in central defenders suggest that this position warrants specific attention regarding injury-prevention strategies. These novel findings highlight the importance of considering training or match exposure when investigating the influence of playing position on injury in ASPs., (© by the National Athletic Trainers' Association, Inc.)

Background: Heritability explains 45-82% of muscle mass and strength variation, yet polygenic models for muscle phenotypes in older women are scarce. Therefore, the objective of the present study was to (1) assess if total genotype predisposition score (GPSTOTAL) for a set of polymorphisms differed between older women with low and high muscle mass, and (2) utilise a data-driven GPS (GPSDD) to predict the variance in muscle size and strength-related phenotypes. Methods: In three-hundred 60- to 91-year-old Caucasian women (70.7 ± 5.7 years), skeletal muscle mass, biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VLACSA), hand grip strength (HGS), and elbow flexion (MVCEF) and knee extension (MVCKE) maximum voluntary contraction were measured. Participants were classified as having low muscle mass if the skeletal muscle index (SMI) < 6.76 kg/m2 or relative skeletal muscle mass (%SMMr) < 22.1%. Genotyping was completed for 24 single-nucleotide polymorphisms (SNPs). GPSTOTAL was calculated from 23 SNPs and compared between the low and high muscle mass groups. A GPSDD was performed to identify the association of SNPs with other skeletal muscle phenotypes. Results: There was no significant difference in GPSTOTAL between low and high muscle mass groups, irrespective of classification based on SMI or %SMMr. The GPSDD model, using 23 selected SNPs, revealed that 13 SNPs were associated with at least one skeletal muscle phenotype: HIF1A rs11549465 was associated with four phenotypes and, in descending number of phenotype associations, ACE rs4341 with three; PTK2 rs7460 and CNTFR rs2070802 with two; and MTHFR rs17421511, ACVR1B rs10783485, CNTF rs1800169, MTHFR rs1801131, MTHFR rs1537516, TRHR rs7832552, MSTN rs1805086, COL1A1 rs1800012, and FTO rs9939609 with one phenotype. The GPSDD with age included as a predictor variable explained 1.7% variance of biceps brachii thickness, 12.5% of VLACSA, 19.0% of HGS, 8.2% of MVCEF, and 9.6% of MVCKE. Conclusions: In older women, GPSTOTAL did not differ between low and high muscle mass groups. However, GPSDD was associated with muscle size and strength phenotypes. Further advancement of polygenic models to understand skeletal muscle function during ageing might become useful in targeting interventions towards older adults most likely to lose physical independence.

Due to the high-velocity collision-based nature of elite rugby league and union, the risk of sustaining a concussion is high. Occurrence of and outcomes following a concussion are probably affected by the interaction of multiple genes in a polygenic manner. This study investigated whether suspected concussion-associated polygenic profiles of elite rugby athletes differed from non-athletes and between rugby union forwards and backs. We hypothesised that a total genotype score (TGS) using eight concussion-associated polymorphisms would be higher in elite rugby athletes than non-athletes, indicating selection for protection against incurring or suffering prolonged effects of, concussion in the relatively high-risk environment of competitive rugby. In addition, multifactor dimensionality reduction was used to identify genetic interactions. Contrary to our hypothesis, TGS did not differ between elite rugby athletes and non-athletes (p ≥ 0.065), nor between rugby union forwards and backs (p = 0.668). Accordingly, the TGS could not discriminate between elite rugby athletes and non-athletes (AUC ~0.5), suggesting that, for the eight polymorphisms investigated, elite rugby athletes do not have a more ‘preferable’ concussion-associated polygenic profile than non-athletes. However, the COMT (rs4680) and MAPT (rs10445337) GC allele combination was more common in rugby athletes (31.7%; p < 0.001) and rugby union athletes (31.8%; p < 0.001) than non-athletes (24.5%). Our results thus suggest a genetic interaction between COMT (rs4680) and MAPT (rs10445337) assists rugby athletes in achieving elite status. These findings need exploration vis-à-vis sport-related concussion injury data and could have implications for the management of inter-individual differences in concussion risk.

Objectives: To investigate if maturity status was associated with injury risk in male academy soccer players., Design: Prospective cohort surveillance study., Setting: Professional soccer academies., Participants: 501 players (aged 9-23 years) from eight academies in England, Spain, Uruguay and Brazil., Main Outcome Measures: Players were grouped by maturity offset as pre-peak height velocity (PHV), circa-PHV, post-PHV or adult. Injury prevalence proportion (IPP) and days missed were recorded for one season per player, with training/match exposure recorded in a sub-sample (n = 166)., Results: IPP for all injuries combined increased with advancing maturity, with circa-PHV (p = 0.032), post-PHV (p < 0.001) and adult (p < 0.001) higher than pre-PHV. IPP was higher in post-PHV and adult than pre-PHV for non-contact (p = 0.001 and p = 0.012), soft-tissue (both p < 0.001), non-contact soft-tissue (p < 0.001 and p = 0.005), muscle (both p < 0.001), thigh (both p < 0.001), ankle (p = 0.035 and p = 0.007) and hamstring injuries (p = 0.041 and p = 0.017). Ligament/tendon IPP was greater in adult versus pre-PHV (p = 0.002). IPP for growth-related injuries was lower in post-PHV than pre-PHV (p = 0.039). Injury incidence rates (n = 166) exhibited similar patterns to IPP in the full cohort., Conclusions: Injury patterns were similar between post-PHV and adult academy players but, crucially, relatively more of these groups suffered injuries compared to pre- and circa-PHV (except growth-related injuries)., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise, related to the preparation of this manuscript. This study was funded as part of a University PhD scholarship., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

It is currently unknown if injury risk is associated with genetic variation in academy soccer players (ASP). We investigated whether nine candidate single nucleotide polymorphisms were associated (individually and in combination) with injury in ASP at different stages of maturation. Saliva samples and one season's injury records were collected from 402 Caucasian male ASP from England, Spain, Uruguay, and Brazil, whose maturity status was defined as pre- or post-peak height velocity (PHV). Pre-PHV COL5A1 rs12722 CC homozygotes had relatively higher prevalence of any musculoskeletal soft tissue (22.4% vs. 3.0%, p = 0.018) and ligament (18.8% vs. 11.8%, p = 0.029) injury than T-allele carriers, while VEGFA rs2010963 CC homozygotes had greater risk of ligament/tendon injury than G-allele carriers. Post-PHV IL6 rs1800795 CC homozygotes had a relatively higher prevalence of any (67.6% vs. 40.6%, p = 0.003) and muscle (38.2% vs. 19.2%, p = 0.013) injuries than G-allele carriers. Relatively more post-PHV EMILIN1 rs2289360 CC homozygotes suffered any injury than CT and TT genotypes (56.4% vs. 40.3% and 32.8%, p = 0.007), while the "protective" EMILIN1 TT genotype was more frequent in post- than pre-PHV ASP (22.3 vs. 10.0%, p = 0.008). Regardless of maturity status, T-alleles of ACTN3 rs1815739 and EMILIN1 rs2289360 were associated with greater absence following ankle injury, while the MMP3 rs679620 T-allele and MYLK rs28497577 GT genotype were associated with greater absence following knee injury. The combination of injury-associated genotypes was greater in injured vs. non-injured ASP. This study is the first to demonstrate that a genetic association exists with injury prevalence in ASP, which differs according to maturity status., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A recent case-control study identified 28 DNA polymorphisms associated with strength athlete status. However, studies of genotype-phenotype design are required to support those findings. The aim of the present study was to investigate both individually and in combination the association of 28 genetic markers with weightlifting performance in Russian athletes and to replicate the most significant findings in an independent cohort of Japanese athletes. Genomic DNA was collected from 53 elite Russian (31 men and 22 women, 23.3 ± 4.1 years) and 100 sub-elite Japanese (53 men and 47 women, 21.4 ± 4.2 years) weightlifters, and then genotyped using PCR or micro-array analysis. Out of 28 DNA polymorphisms, LRPPRC rs10186876 A, MMS22L rs9320823 T, MTHFR rs1801131 C, and PHACTR1 rs6905419 C alleles positively correlated ( p < 0.05) with weightlifting performance (i.e., total lifts in snatch and clean and jerk in official competitions adjusted for sex and body mass) in Russian athletes. Next, using a polygenic approach, we found that carriers of a high (6-8) number of strength-related alleles had better competition results than carriers of a low (0-5) number of strength-related alleles (264.2 (14.7) vs. 239.1 (21.9) points; p = 0.009). These findings were replicated in the study of Japanese athletes. More specifically, Japanese carriers of a high number of strength-related alleles were stronger than carriers of a low number of strength-related alleles (212.9 (22.6) vs. 199.1 (17.2) points; p = 0.0016). In conclusion, we identified four common gene polymorphisms individually or in combination associated with weightlifting performance in athletes from East European and East Asian geographic ancestries.

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.

Background: The aim of the study was to establish the bone and body composition characteristics of high-level athletes with and without a history of stress fracture injury., Methods: Overall, 279 high-level athletes (212 men, 67 women) (age 28.0±9.2 years; body mass 75.0±17.4 kg; height 1.78±0.10 m) and 112 non-athletic controls (60 women, 52 men) 36.2±15.0 years; 70.9±12.9 kg; 1.71±0.10 m) were assessed by DXA to establish their bone mineral density and content, body fat and lean mass. Athletes completed a questionnaire detailing their stress fracture history., Results: There were no differences in whole-body bone mineral density (men 1.41±0.12 g/cm 2 , women 1.19±0.09 g/cm 2 ), bone mineral content (men 3709±626 g, women 2263±290 g), body fat (men 16.3±5.0%,women 23.0±4.6%) and lean mass (men 65.4±9.9 kg, women 38.7±3.6 kg) between athletes with a history of stress fracture (34 men, 16 women) and those without (176 men, 40 women)., Conclusions: DXA derived bone and body composition characteristics were not independent risk factors for stress fracture injury in high-level athletes. This study in a large cohort of high-level athletes provides normative bone and body composition values that can be used as a benchmark for researchers and applied practitioners.

Obesity may aggravate the effects of sarcopenia on skeletal muscle structure and function in the elderly, but no study has attempted to identify the gene variants associated with sarcopenia in obese women. Therefore, the aims of the present study were to: (1) describe neuromuscular function in sarcopenic and non-sarcopenic women with or without obesity; (2) identify gene variants associated with sarcopenia in older obese women. In 307 Caucasian women (71 ± 6 years, 66.3 ± 11.3 kg), skeletal muscle mass was estimated using bioelectric impedance, and function was tested with a 30 s one-leg standing-balance test. Biceps brachii thickness and vastus lateralis cross-sectional area (VL ACSA ) were measured with B-mode ultrasonography. Handgrip strength, maximum voluntary contraction elbow flexion (MVC EF ), and knee extension torque (MVC KE ) were measured by dynamometry, and MVC KE /VL ACSA was calculated. Genotyping was performed for 24 single-nucleotide polymorphisms (SNPs), selected based on their previous associations with muscle-related phenotypes. Based on sarcopenia and obesity thresholds, groups were classified as sarcopenic obese, non-sarcopenic obese, sarcopenic non-obese, or non-sarcopenic non-obese. A two-way analysis of covariance was used to assess the main effects of sarcopenia and obesity on muscle-related phenotypes and binary logistic regression was performed for each SNP to investigate associations with sarcopenia in obesity. There were no significant obesity * sarcopenic status interactions for any of the investigated muscle-related phenotypic parameters. Neither sarcopenia nor obesity had a significant effect on biceps brachii thickness, but sarcopenia was associated with lower VL ACSA ( p = 0.003). Obesity was associated with lower MVC EF ( p = 0.032), MVC KE ( p = 0.047), and MVC KE /VL ACSA ( p = 0.012) with no significant effect of sarcopenia. Adjusted for age and height, three SNPs ( ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) were associated with sarcopenia in obese participants. Sarcopenia was associated with a smaller muscle size, while obesity resulted in a lower muscle quality irrespective of sarcopenia. Three gene variants ( ACTN3 rs1815739, MTHFR rs1801131, and MTHFR rs1537516) suspected to affect muscle function, homocysteine metabolism, or DNA methylation, respectively, were associated with sarcopenia in obese elderly women. Understanding the skeletal muscle features affected by sarcopenia and obesity, and identification of genes related to sarcopenia in obese women, may facilitate early detection of individuals at particular risk of sarcopenic obesity.

Although multiple nutrients have shown protective effects with regard to preserving muscle function, the recommended amount of dietary protein and other nutrients profile on older adults for maintenance of high muscle mass is still debatable. The aims of this paper were to: (1) identify dietary differences between older women with low and high relative skeletal muscle mass, and (2) identify the minimal dietary protein intake associated with high relative skeletal muscle mass and test the threshold ability to determine an association with skeletal muscle phenotypes. Older women ( n = 281; 70 ± 7 years, 65 ± 14 kg), with both low and high relative skeletal muscle mass groups, completed a food questionnaire. Skeletal muscle mass, fat-free mass (FFM), biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VL ACSA ), handgrip strength (HGS), maximum elbow flexion torque (MVC EF ), maximum knee extension torque (MVC KE ), muscle quality (HGS/Body mass), and fat mass were measured. Older women with low relative skeletal muscle mass had a lower daily intake of protein, iodine, polyunsaturated fatty acid (PUFA), Vit E, manganese, milk, fish, nuts and seeds ( p < 0.05) compared to women with high relative skeletal muscle mass. The minimum required dietary protein intake for high relative skeletal muscle mass was 1.17 g/kg body mass/day (g/kg/d) (sensitivity: 0.68; specificity: 0.62). Women consuming ≥1.17 g/kg/d had a lower BMI (B = -3.9, p < 0.001) and fat mass (B = -7.8, p < 0.001), and a higher muscle quality (B = 0.06, p < 0.001). The data indicate that to maintain muscle mass and function, older women should consume ≥1.17 g/kg/d dietary protein, through a varied diet including milk, fish and nuts that also contain polyunsaturated fatty acid (PUFA) and micronutrients such as iodine, Vit E and manganese.

Background: Identification of simple screening tools for detecting lower skeletal muscle mass may be beneficial for planning effective interventions in the elderly., Aims: We aimed to (1) establish a threshold for one-leg standing balance test (OLST) time for low muscle mass, and (2) test the ability of that threshold to assess muscular impairments in a poor balance group., Methods: Eyes-open OLST (maximum duration 30 s) was performed with right and left legs in 291 women (age 71 ± 6 years). OLST time was calculated as the sum of the OLST time of right and left legs. Fat-free mass (FFM), skeletal muscle mass (SMM), fat mass, biceps brachii and vastus lateralis sizes; handgrip strength (HGS), elbow flexion maximum torque (MVC EF ) and knee extension maximum torque (MVC KE ) were measured. Muscle quality was calculated as MVC KE /FFM and physical activity was assessed by questionnaire. Low muscle mass was defined as SMM relative of 22.1%, a previously established threshold for pre-sarcopenia., Results: The OLST threshold time to detect low muscle mass was 55 s (sensitivity: 0.63; specificity: 0.60). The poor balance group (OLST < 55 s) had higher fat mass (3.0%, p < 0.001), larger VL thickness (5.1%, p = 0.016), and lower HGS (- 10.2%, p < 0.001), MVC EF (- 8.2%, p = 0.003), MVC KE (- 9.5%, p = 0.012), MVC KE /FFM (- 11.0%, p = 0.004) and physical activity (- 8.0%, p = 0.024) compared to the normal balance group. While after adjusting age, the differences exist for HGS, fat mass and VL thickness only., Discussion: An OLST threshold of 55 s calculated as the summed score from both legs discriminated pre-sarcopenic characteristics among active, community-dwelling older women with limited potential (sensitivity 0.63, specificity 0.60)., Conclusion: OLST, which can be performed easily in community settings without the need for more complex muscle mass measurement, may help identify women at risk of developing sarcopenia.

Elite rugby league and union have some of the highest reported rates of concussion (mild traumatic brain injury) in professional sport due in part to their full-contact high-velocity collision-based nature. Currently, concussions are the most commonly reported match injury during the tackle for both the ball carrier and the tackler (8-28 concussions per 1000 player match hours) and reports exist of reduced cognitive function and long-term health consequences that can end a playing career and produce continued ill health. Concussion is a complex phenotype, influenced by environmental factors and an individual's genetic predisposition. This article reviews concussion incidence within elite rugby and addresses the biomechanics and pathophysiology of concussion and how genetic predisposition may influence incidence, severity and outcome. Associations have been reported between a variety of genetic variants and traumatic brain injury. However, little effort has been devoted to the study of genetic associations with concussion within elite rugby players. Due to a growing understanding of the molecular characteristics underpinning the pathophysiology of concussion, investigating genetic variation within elite rugby is a viable and worthy proposition. Therefore, we propose from this review that several genetic variants within or near candidate genes of interest, namely APOE , MAPT , IL6R , COMT , SLC6A4 , 5-HTTLPR , DRD2 , DRD4 , ANKK1 , BDNF and GRIN2A , warrant further study within elite rugby and other sports involving high-velocity collisions.

There is a scarcity of studies that have investigated the role of multiple single nucleotide polymorphisms (SNPs) on a range of muscle phenotypes in an elderly population. The present study investigated the possible association of 24 SNPs with skeletal muscle phenotypes in 307 elderly Caucasian women (aged 60-91 years, 66.3 ± 11.3 kg). Skeletal muscle phenotypes included biceps brachii thickness, vastus lateralis cross-sectional areas, maximal hand grip strength, isometric knee extension and elbow flexion torque. Genotyping for 24 SNPs, chosen on their skeletal muscle structural or functional links, was conducted on DNA extracted from blood or saliva. Of the 24 SNPs, 10 were associated with at least one skeletal muscle phenotype. HIF1A rs11549465 was associated with three skeletal muscle phenotypes and PTK2 rs7460 and ACVR1B rs10783485 were each associated with two phenotypes. PTK2 rs7843014, COL1A1 rs1800012, CNTF rs1800169, NOS3 rs1799983, MSTN rs1805086, TRHR rs7832552 and FTO rs9939609 were each associated with one. Elderly women possessing favourable genotypes were 3.6-13.2% stronger and had 4.6-14.7% larger muscle than those with less favourable genotypes. These associations, together with future work involving a broader range of SNPs, may help identify individuals at particular risk of an age-associated loss of independence.

The integration of genetic and environmental factors that regulate the gene expression patterns associated with exercise adaptation is mediated by epigenetic mechanisms. The organisation of the human genome within three-dimensional space, known as chromosome conformation, has recently been shown as a dynamic epigenetic regulator of gene expression, facilitating the interaction of distal genomic regions due to tight and regulated packaging of chromosomes in the cell nucleus. Technological advances in the study of chromosome conformation mean a new class of biomarker-the chromosome conformation signature (CCS)-can identify chromosomal interactions across several genomic loci as a collective marker of an epigenomic state. Investigative use of CCSs in biological and medical research shows promise in identifying the likelihood that a disease state is present or absent, as well as an ability to prospectively stratify individuals according to their likely response to medical intervention. The association of CCSs with gene expression patterns suggests that there are likely to be CCSs that respond, or regulate the response, to exercise and related stimuli. The present review provides a contextual background to CCS research and a theoretical framework discussing the potential uses of this novel epigenomic biomarker within sport and exercise science and medicine.

Objectives: To identify the most common injury types/locations in high-level male youth soccer players (YSP)., Design: Prospective cohort surveillance study., Setting: Professional soccer club academies., Participants: Six hundred and twenty-four high-level male YSP [Under 9 (U9) to U23 year-old age groups] from academies in England, Spain, Uruguay and Brazil., Main Outcome Measures: Injury type, location and severity were recorded during one season. Injury severity was compared between age groups, while injury type and location were compared between nations., Results: Four hundred and forty-three training or match injuries were recorded, giving an injury rate of 0.71 per player. Non-contact injuries were most common (58.5%), with most (44.2%) resolved between 8 and 28 days. Most injuries (75.4%) occurred in the lower limbs, with muscle (29.6%) the most commonly injured tissue. U14 and U16 suffered a greater number of severe injuries relative to U12 and U19/U20/U23/Reserves. Tendon injury rate was higher in Brazil vs. Spain (p < 0.05), with low back/sacrum/pelvis injury rate highest in Spain (p < 0.05)., Conclusions: The proportion of severe injuries in U14 and U16 suggests YSP injury risk is maturation-dependent. Minimal differences in type and location between high-level YSP from four different countries suggest injury rates in this population are geographically similar., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Brazier, J, Antrobus, M, Stebbings, GK, Day, SH, Callus, P, Erskine, RM, Bennett, MA, Kilduff, LP, and Williams, AG. Anthropometric and physiological characteristics of elite male rugby athletes. J Strength Cond Res 34(6): 1790-1801, 2020-This is the first article to review the anthropometric and physiological characteristics required for elite rugby performance within both rugby union (RU) and rugby league (RL). Anthropometric characteristics such as height and body mass, and physiological characteristics such as speed and muscular strength, have previously been advocated as key discriminators of playing level within rugby. This review aimed to identify the key anthropometric and physiological properties required for elite performance in rugby, distinguishing between RU and RL, forwards and backs and competitive levels. There are differences between competitive standards such that, at the elite level, athletes are heaviest (RU forwards ∼111 kg, backs ∼93 kg; RL forwards ∼103 kg, backs ∼90 kg) with lowest % body fat (RU forwards ∼15%, backs ∼12%; RL forwards ∼14%, backs ∼11%), they have most fat-free mass and are strongest (back squat: RU forwards ∼176 kg, backs ∼157 kg; RL forwards ∼188 kg, backs ∼168 kg; bench press: RU forwards ∼131 kg, backs ∼118 kg; RL forwards ∼122 kg, backs ∼113 kg) and fastest (10 m: RU forwards ∼1.87 seconds, backs ∼1.77 seconds; 10 m: RL forwards ∼1.9 seconds, backs ∼1.83 seconds). We also have unpublished data that indicate contemporary RU athletes have less body fat and are stronger and faster than the published data suggest. Regardless, well-developed speed, agility, lower-body power, and strength characteristics are vital for elite performance, probably reflect both environmental (training, diet, etc.) and genetic factors, distinguish between competitive levels, and are therefore important determinants of elite status in rugby.

This article reviews tendon and ligament injury incidence and severity within elite rugby union and rugby league. Furthermore, it discusses the biological makeup of tendons and ligaments and how genetic variation may influence this and predisposition to injury. Elite rugby has one of the highest reported injury incidences of any professional sport. This is likely due to a combination of well-established injury surveillance systems and the characteristics of the game, whereby high-impact body contact frequently occurs, in addition to the high intensity, multispeed and multidirectional nature of play. Some of the most severe of all these injuries are tendon and ligament/joint (non-bone), and therefore, potentially the most debilitating to a player and playing squad across a season or World Cup competition. The aetiology of these injuries is highly multi-factorial, with a growing body of evidence suggesting that some of the inter-individual variability in injury susceptibility may be due to genetic variation. However, little effort has been devoted to the study of genetic injury traits within rugby athletes. Due to a growing understanding of the molecular characteristics underpinning the aetiology of injury, investigating genetic variation within elite rugby is a viable and worthy proposition. Therefore, we propose several single nucleotide polymorphisms within candidate genes of interest; COL1A1, COL3A1, COL5A1, MIR608, MMP3, TIMP2, VEGFA, NID1 and COLGALT1 warrant further study within elite rugby and other invasion sports.

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.

The purpose of the study was to investigate the current use of genetic testing in UK elite sport and assess how genetic testing might be received by those employed in elite sport. Seventy-two elite athletes and 95 support staff at UK sports clubs and governing bodies completed an online survey of 11 questions concerning their experience of genetic testing and beliefs regarding the use of genetic testing in sport. Genetic testing related to sports performance and injury susceptibility is conducted in UK elite sport, albeit by a relatively small proportion of athletes (≤17%) and support staff (≤8%). Athletes and their support staff agree that genetics are important in determining elite status (≥79%) and appear willing to engage in genetic testing for individualising training to improve sport performance and reduce injury risk. Opinion was divided on whether genetic information should be used to identify talented athletes and influence selection, eligibility or employment status. Genetic testing for sports performance and injury susceptibility occurs in UK elite sport, however it is not commonly conducted. There is a belief that genetics is an important factor in determining an athlete and there is a willingness to engage in genetic testing for sports performance and injury susceptibility.

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.

Background: Two common single nucleotide polymorphisms within the COL5A1 gene (SNPs; rs12722 C/T and rs3196378 C/A) have previously been associated with tendon and ligament pathologies. Given the high incidence of tendon and ligament injuries in elite rugby athletes, we hypothesised that both SNPs would be associated with career success., Results: In 1105 participants (RugbyGene project), comprising 460 elite rugby union (RU), 88 elite rugby league athletes and 565 non-athlete controls, DNA was collected and genotyped for the COL5A1 rs12722 and rs3196378 variants using real-time PCR. For rs12722, the injury-protective CC genotype and C allele were more common in all athletes (21% and 47%, respectively) and RU athletes (22% and 48%) than in controls (16% and 41%, P ≤ 0.01). For rs3196378, the CC genotype and C allele were overrepresented in all athletes (23% and 48%) and RU athletes (24% and 49%) compared with controls (16% and 41%, P ≤ 0.02). The CC genotype in particular was overrepresented in the back and centres (24%) compared with controls, with more than twice the odds (OR = 2.25, P = 0.006) of possessing the injury-protective CC genotype. Furthermore, when considering both SNPs simultaneously, the CC-CC SNP-SNP combination and C-C inferred allele combination were higher in all the athlete groups (≥18% and ≥43%) compared with controls (13% and 40%; P = 0.01). However, no genotype differences were identified for either SNP when RU playing positions were compared directly with each other., Conclusion: It appears that the C alleles, CC genotypes and resulting combinations of both rs12722 and rs3196378 are beneficial for rugby athletes to achieve elite status and carriage of these variants may impart an inherited resistance against soft tissue injury, despite exposure to the high-risk environment of elite rugby. These data have implications for the management of inter-individual differences in injury risk amongst elite athletes.

Introduction: Muscle weakness determines functional impairment in spastic cerebral palsy (SCP). Measurement of specific force (SF) allows for strength comparison with unimpaired populations (controls) accounting for neural (activation and coactivation), architectural (fascicle length and pennation angle), and structural differences (moment arm length)., Methods: Medial gastrocnemius (MG) SF (and its determinants) was assessed in both paretic and non-paretic legs of 11 men with SCP and 11 age-matched controls during plantarflexion maximal voluntary isometric contraction (MVIC)., Results: SCP fascicles were 28% longer than control fascicles (P < 0.05). Pennation angle of SCP patients was 41% smaller than in controls. The physiological cross-sectional area of SCP MG patients was 47% smaller than in controls (P < 0.05). There was no difference in SF between controls and SCP patients., Conclusions: Weakness in SCP is primarily attributable to deficits in agonist activation and muscle size; consequently, SF measured in the MG is similar between SCP and controls. Muscle Nerve 56: 298-306, 2017., (© 2016 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.)

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., (Copyright © 2016 the American Physiological Society.)

This paper addresses practical and ethical considerations regarding genetic tests to predict performance and/or risk of exercise-related injury or illness. Various people might wish to conduct sport-related genetic tests for a variety of reasons. For example, an individual might seek personal genetic information to help guide their own sport participation. A sports coach might wish to test young athletes to aid team selection or individualize training. A physician might want to predict the risk of injury or illness in athletes and advise regarding selection or preventative measures. An insurance company might seek to estimate the risk of career-threatening injury for athletes based partly on genetic information. Whilst this information is, in part, encoded in our DNA sequence, the available tests allow generally only a poor prediction of the aforementioned variables. In other words, the current genetic tests and analysis methods are not powerful enough to inform important decisions in sport to a substantial degree. It is particularly disappointing that more than half of the commercially available genetic tests related to exercise and sport do not appear to identify publicly the genetic variants they assess, making scrutiny by academic scholars and consumers (or their representatives) impossible. There are also challenging ethical issues to consider. For example, the imposition of genetic tests on individuals (especially young people) by third parties is potentially susceptible to abuse. Scientists and practitioners should understand the limitations of the tests currently available, the ethical concerns and the importance of counselling before and after testing so that they are only used in a responsible manner., (© 2016 S. Karger AG, Basel.)

Despite numerous attempts to discover genetic variants associated with elite athletic performance, an individual's 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., (© 2016 S. Karger AG, Basel.)

This article introduces some aspects of sports genomics in a rugby union context, considers the rugby-specific genetic data in the published literature and outlines the next research steps required if the potential applications of genetic technology in rugby union, also identified here, are to become possible. A substantial proportion of the inter-individual variation for many traits related to rugby performance, including strength, short-term muscle power, VO2 max, injury susceptibility and the likelihood of being an elite athlete is inherited and can be investigated using molecular genetic techniques. In sports genomics, significant efforts have been made in recent years to develop large DNA biobanks of elite athletes for detailed exploration of the heritable bases of those traits. However, little effort has been devoted to the study of rugby athletes, and most of the little research that has focused on rugby was conducted with small cohorts of non-elite players. With steadily growing knowledge of the molecular mechanisms underpinning complex performance traits and the aetiology of injury, investigating sports genomics in the context of rugby is now a viable proposition and a worthwhile endeavour. The RugbyGene project we describe briefly in this article is a multi-institutional research collaboration in rugby union that will perform molecular genetic analyses of varying complexity. Genetic tests could become useful tools for rugby practitioners in the future and provide complementary and additional information to that provided by the non-genetic tests currently used.

Background/aim: Gene variants encoding for proteins involved in homeostatic processes within tendons may influence its material and mechanical properties in humans. The purpose of this study was to examine the association between three polymorphisms of the MMP3 gene, (rs679620, rs591058 and rs650108) and patellar tendon dimensional and mechanical properties in vivo., Methods: One hundred and sixty, healthy, recreationally-active, Caucasian men and women, aged 18-39 were recruited. MMP3 genotype determined using real-time PCR was used to select 84 participants showing greatest genetic differences to complete phenotype measurements. Patellar tendon dimensions (volume) and functional (elastic modulus) properties were assessed in vivo using geometric modelling, isokinetic dynamometry, electromyography and ultrasonography., Results: No significant associations were evident between the completely linked MMP3 rs591058 and rs679620 gene variants, and closely linked rs650108 gene variant, and either patellar tendon volume (rs679620, P = 0.845; rs650108, P = 0.984) or elastic modulus (rs679620, P = 0.226; rs650108, P = 0.088). Similarly, there were no associations with the Z-score that combined those dimension and functional properties into a composite value (rs679620, P = 0.654; rs650108, P = 0.390). Similarly, no association was evident when comparing individuals with/without the rarer alleles (P > 0.01 in all cases)., Conclusions: Patellar tendon properties do not seem to be influenced by the MMP3 gene variants measured. Although these MMP3 gene variants have previously been associated with the risk of tendon pathology, that association is unlikely to be mediated via underlying tendon dimensional and functional properties.

Introduction: Inter-individual variability in measurements of muscle strength and its determinants was identified to: (1) produce a normative data set describing the normal range and (2) determine whether some measurements are more informative than others when evaluating inter-individual differences., Methods: Functional and morphological characteristics of the vastus lateralis were measured in 73 healthy, untrained adult men., Results: Inter-individual variability (coefficient of variation) was greater for isometric maximal voluntary contraction (MVC) torque (18.9%) compared with fascicle force (14.6%; P=0.025) and physiological cross-sectional area (PCSA; 17.2%) compared with anatomical cross-sectional area (ACSA, 13.0%; P<0.0005). The relationship between ACSA and isometric MVC torque (r(2)  =0.56) was weaker than that between PCSA and fascicle force (r(2)  =0.68)., Conclusions: These results provide a normative data set on inter-individual variability in a variety of muscle strength-related measurements and illustrate the benefit of using more stringent measures of muscle properties. Muscle Nerve 49: 879-886, 2014., (Copyright © 2013 Wiley Periodicals, Inc.)

Accurate assessment of muscle-tendon forces in vivo requires knowledge of the muscle-tendon moment arm. Dual-energy X-ray absorptiometry (DXA) can produce 2D images suitable for visualising both tendon and bone, thereby potentially allowing the moment arm to be measured but there is currently no validated DXA method for this purpose. The aims of this study were (i) to compare in vivo measurements of the patellar tendon moment arm (dPT) assessed from 2D DXA and magnetic resonance (MR) images and (ii) to compare the reliability of the two methods. Twelve healthy adults (mean ± SD: 31.4 ± 9.5 yr; 174.0 ± 9.5 cm; 76.2 ± 16.6 kg) underwent two DXA and two MR scans of the fully extended knee at rest. The tibiofemoral contact point (TFCP) was used as the centre of joint rotation in both techniques, and the dPT was defined as the perpendicular distance from the patellar tendon axis to the TFCP. The dPT was consistently longer when assessed via DXA compared to MRI (+3.79 ± 1.25 mm or +9.78 ± 3.31%; P<0.001). The test-retest reliability of the DXA [CV=2.13%; ICC=0.94; ratio limits of agreement (RLA)=1.01 (*/÷1.07)] and MR [(CV=2.27%; ICC=0.96; RLA=1.00 (*/÷1.07)] methods was very high and comparable between techniques. Moreover, the RLA between the mean DXA and MRI dPT values [1.097 (*/÷1.061)] demonstrated very strong agreement between the two methods. In conclusion, highly reproducible dPT measurements can be determined from DXA imaging with the knee fully extended at rest. This has implications for the calculation of patellar tendon forces in vivo where MR equipment is not available., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Gene variants encoding for proteins involved in homeostatic processes within tendons may influence its material and mechanical properties in humans. The purpose of this study was to examine the association between one such gene variant, gene encoding collagen type V alpha 1 chain (COL5A1) rs12722, and patellar tendon dimensions and mechanical properties in vivo., Methods: Eighty-four recreationally active, Caucasian, men and women, aged 18-39, with no history of injuries to the knee and a body mass index between 18.5 and 30 were recruited. Women were not recruited if they were pregnant or using any form of hormone-based contraception. The COL5A1 rs12722 genotype was determined using real-time polymerase chain reaction. Patellar tendon dimensions (volume) and functional (elastic modulus) properties were assessed in vivo using geometric modelling, isokinetic dynamometry, electromyography and ultrasonography., Results: After adjustments for non-genetic factors, no significant associations were evident between the COL5A1 rs12722 gene variant and either patellar tendon volume (P = 0.933) or elastic modulus (P = 0.206), nor with a calculated Z score that combined these dimensional and functional properties into a composite value (P = 0.647). Similarly, no association was evident when comparing individuals with/without the rare C allele (volume, P = 0.883; elastic modulus, P = 0.129; Z score, P = 0.631)., Conclusions: Tendon properties do not seem to be influenced by the COL5A1 rs12722 gene variant. Although the COL5A1 rs12722 polymorphism has previously been associated with the risk of tendon pathology, that association is unlikely to be mediated via underlying tendon dimensional and functional properties.

Introduction: Muscle weakness is present in the paretic limbs of individuals with cerebral palsy (CP). We aimed to determine what neuromuscular factors contribute to weakness in adults with CP during isometric maximal voluntary contractions (iMVCs)., Methods: Gastrocnemius anatomical cross-sectional area (ACSA) and agonist and antagonist activation were measured in 11 CP and 11 control adult men during plantarflexion iMVC., Results: Plantarflexion iMVC torque of the paretic leg was 42% and 52% less than in the non-paretic and control limbs, respectively. The paretic gastrocnemius ACSA was smaller than in the control group only. Paretic agonist activation was less than the non-paretic and control groups, whereas antagonist coactivation was higher. Multiple regression analysis revealed muscle activation accounted for 57% of variation in paretic plantarflexion iMVC torque., Conclusions: In individuals with CP, muscle weakness in the paretic limb is attributed primarily to impaired neural activation and, to a lesser degree, ACSA., (Copyright © 2013 Wiley Periodicals, Inc.)

Hypoxia-inducible factor-1α (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.

Objective: The FTO A/T polymorphism (rs9939609) is a strong candidate to influence obesity-related traits. Elite athletes from many different sporting disciplines are characterized by low body fat. Therefore, the aim of this study was to assess whether athletic status is associated with the FTO A/T polymorphism., Subjects and Methods: A large cohort of European Caucasians from Poland, Russia and Spain were tested to examine the association between FTO A/T polymorphism (rs9939609) and athletic status. A total of 551 athletes were divided by type of sport (endurance athletes, n = 266 vs. sprint/power athletes, n = 285) as well as by level of competition (elite-level vs. national-level). The control group consisted of 1,416 ethnically-matched, non-athletic participants, all Europeans. Multinomial logistic regression analyses were conducted to assess the association between FTO A/T genotypes and athletic status/competition level., Results: There were no significantly greater/lesser odds of harbouring any type of genotype when comparing across athletic status (endurance athletes, sprint/power athletes or control participants). These effects were observed after controlling for sex and nationality. Furthermore, no significantly greater/lesser odds ratios were observed for any of the genotypes in respect to the level of competition (elite-level vs. national-level)., Conclusion: The FTO A/T polymorphism is not associated with elite athletic status in the largest group of elite athletes studied to date. Large collaborations and data sharing between researchers, as presented here, are strongly recommended to enhance the research in the field of exercise genomics.

The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5-90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40-50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin-NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.

The protein tyrosine kinase-2 (PTK2) gene encodes focal adhesion kinase, a structural protein involved in lateral transmission of muscle fiber force. We investigated whether single-nucleotide polymorphisms (SNPs) of the PTK2 gene were associated with various indexes of human skeletal muscle strength and the interindividual variability in the strength responses to resistance training. We determined unilateral knee extension single repetition maximum (1-RM), maximum isometric voluntary contraction (MVC) knee joint torque, and quadriceps femoris muscle specific force (maximum force per unit physiological cross-sectional area) before and after 9 wk of knee extension resistance training in 51 untrained young men. All participants were genotyped for the PTK2 intronic rs7843014 A/C and 3'-untranslated region (UTR) rs7460 A/T SNPs. There were no genotype associations with baseline measures or posttraining changes in 1-RM or MVC. Although the training-induced increase in specific force was similar for all PTK2 genotypes, baseline specific force was higher in PTK2 rs7843014 AA and rs7460 TT homozygotes than in the respective rs7843014 C- (P = 0.016) and rs7460 A-allele (P = 0.009) carriers. These associations between muscle specific force and PTK2 SNPs suggest that interindividual differences exist in the way force is transmitted from the muscle fibers to the tendon. Therefore, our results demonstrate for the first time the impact of genetic variation on the intrinsic strength of human skeletal muscle.

Uncoupling proteins 2 and 3 (UCP2 and UCP3) may negatively regulate mitochondrial ATP synthesis and, through this, influence human physical performance. However, human data relating to both these issues remain sparse. Examining the association of common variants in the UCP3/2 locus with performance phenotypes offers one means of investigation. The efficiency of skeletal muscle contraction, delta efficiency (DE), was assessed by cycle ergometry in 85 young, healthy, sedentary adults both before and after a period of endurance training. Of these, 58 were successfully genotyped for the UCP3-55C>T (rs1800849) and 61 for the UCP2-866G>A (rs659366) variant. At baseline, UCP genotype was unrelated to any physical characteristic, including DE. However, the UCP2-866G>A variant was independently and strongly associated with the DE response to physical training, with UCP2-866A allele carriers exhibiting a greater increase in DE with training (absolute change in DE of -0.2 ± 3.6% vs. 1.7 ± 2.8% vs. 2.3 ± 3.7% for GG vs. GA vs. AA, respectively; P = 0.02 for A allele carriers vs. GG homozygotes). In multivariate analysis, there was a significant interaction between UCP2-866G>A and UCP3-55C>T genotypes in determining changes in DE (adjusted R(2) = 0.137; P value for interaction = 0.003), which was independent of the effect of either single polymorphism or baseline characteristics. In conclusion, common genetic variation at the UCP3/2 gene locus is associated with training-related improvements in DE, an index of skeletal muscle performance. Such effects may be mediated through differences in the coupling of mitochondrial energy transduction in human skeletal muscle, but further mechanistic studies are required to delineate this potential role.

It is generally accepted that muscle fibre composition may influence physical performance. The α-actinin-3 (ACTN3) gene R577X polymorphism is suspected to be one of the contributing gene variations in the determination of muscle fibre type composition and athletic status. In the present study, we examined the dependence of average preferred racing distance (PRD) on muscle fibre type composition of the vastus lateralis muscle in 34 subelite Russian speed skaters (20 men and 14 women) who competed in races of different length (500-10,000 m). We also investigated the association between the ACTN3 polymorphism and muscle fibre characteristics in 94 subjects (60 physically active healthy men and 34 speed skaters), as well as the relationship between PRD and ACTN3 genotype in 115 subelite and elite speed skaters. In addition, ACTN3 genotype and allele frequencies of the 115 speed skaters were compared with 1301 control subjects. The ACTN3 XX genotype frequency was significantly lower in sprinters (n = 39) compared with control subjects (2.6 versus 14.5%; P = 0.034). We observed a positive relationship between PRD and the proportion of slow-twitch muscle fibres that was close to linear, but better fitted a logarithmic curve (r = 0.593, P < 0.0005). The ACTN3 R577X polymorphism was associated with muscle fibre composition (slow-twitch fibres: RR genotype, 51.7 (12.8)%; RX, 57.4 (13.2)%; XX 61.5 (16.3)%; = 0.215; P = 0.049) in the overall muscle biopsy group, and with PRD of all athletes ( = 0.24, P = 0.010), indicating thatACTN3 XX genotype carriers exhibit a higher proportion of slow-twitch fibres and prefer to skate long-distance races. However, the majority of the association between muscle fibre type and PRD was independent of ACTN3 genotype. In conclusion, the ACTN3 R577X polymorphism is associated with preferred racing distance in speed skaters and muscle fibre type composition. Thus, it is probably partly via associations with fibre type that the R577X polymorphism contributes to a small but perhaps important component of the ability to perform at a high level in speed skating.

Environmental and genetic factors influence muscle function, resulting in large variations in phenotype between individuals. Multiple genetic variants (polygenic in nature) are thought to influence exercise-related phenotypes, yet how the relevant polymorphisms combine to influence muscular strength in individuals and populations is unclear. In this analysis, 22 genetic polymorphisms were identified in the literature that have been associated with muscular strength and power phenotypes. Using typical genotype frequencies, the probability of any given individual possessing an "optimal" polygenic profile was calculated as 0.0003% for the world population. Future identification of additional polymorphisms associated with muscular strength phenotypes would most likely reduce that probability even further. To examine the genetic potential for muscular strength within a human population, a "total genotype score" was generated for each individual within a hypothetical population of one million. The population expressed high similarity in polygenic profile with no individual differing by more than seven genotypes from a typical profile. Therefore, skeletal muscle strength potential within humans appears to be limited by polygenic profile similarity. Future research should aim to replicate more genotype-phenotype associations for muscular strength, because only five common genetic polymorphisms identified to date have positive replicated findings.

It is not known why in vivo muscle specific tension increases following resistance training in humans but changes in muscle fibre-type composition, increased single-fibre specific tension or lateral force transmission might provide explanations. Lateral force transmission would increase specific tension but decrease contraction velocity, thus not affecting maximal power per unit muscle volume. In vivo muscle specific tension, power output and muscle volume were determined in the quadriceps femoris of 42 young men, while myosin heavy chain (MyHC) isoform composition, single-fibre (SF) specific tension, SF maximal shortening velocity (V(max)) and SF peak power (W(max)) of the vastus lateralis were established in a subsample (n = 17) before and after high-intensity leg-extension resistance training (3 sessions week(-1) for 9 weeks). Following training, in vivo muscle specific tension increased by 17% but the power output/muscle volume ratio remained unaltered. Furthermore, there was no relationship between the training-induced decrease in MyHC IIX and the change in specific tension in vivo. In addition, SF specific tension, V(max) and W(max) were unchanged following training. In conclusion, a change in fibre-type composition does not explain the increased in vivo specific tension, nor does it seem likely that increased myofilament packing occurred with resistance training. However, an unchanged in vivo power per unit muscle volume is in accordance with the notion of enhanced lateral force transmission after strength training.