Genetic Associations With Acceleration, Change of Direction, Jump Height, and Speed in English Academy Football Players.

ABSTRACT: McAuley, ABT, Hughes, DC, Tsaprouni, LG, Varley, I, Suraci, B, Bradley, B, Baker, J, Herbert, AJ, and Kelly, AL. Genetic associations with acceleration, change of direction, jump height, and speed in English academy football players. J Strength Cond Res 38(2): 350-359, 2024-High-intensity movements and explosive actions are commonly assessed during athlete development in football (soccer). Although many environmental factors underpin these power-orientated traits, research suggests that there is also a sizeable genetic component. Therefore, this study examined the association of 22 single-nucleotide polymorphisms (SNPs) with acceleration, change of direction, jump height, and speed in academy football players. One hundred and forty-nine, male, under-12 to under-23 football players from 4 English academies were examined. Subjects performed 5-, 10-, 20-, and 30-m sprints, countermovement jumps (CMJs), and the 5-0-5 agility test. Simple linear regression was used to analyze individual SNP associations, whereas both unweighted and weighted total genotype scores (TGS; TWGS) were computed to measure the combined influence of all SNPs. To control for multiple testing, a Benjamini-Hochberg false discovery rate of 0.05 was applied to all genotype model comparisons. In isolation, the GALNT13 (rs10196189) G allele and IL6 (rs1800795) G/G genotype were associated with faster (∼4%) 5-, 10-, and 20-m sprints and higher (∼16%) CMJs, respectively (p < 0.001). Furthermore, the TGS and TWGS significantly correlated with all performance assessments, explaining between 6 and 33% of the variance (p < 0.001). This study demonstrates that some genetic variants are associated with power-orientated phenotypes in youth football players and may add value toward a future polygenic profile of physical performance.

Maturity-Associated Polygenic Profiles of under 12-16-Compared to under 17-23-Year-Old Male English Academy Football Players.

The purpose of this study was to examine polygenic profiles previously associated with maturity timing in male academy football players across different age phases. Thus, 159 male football players from four English academies (U12-16, n = 86, aged 13.58 ± 1.58 years; U17-23, n = 73, aged 18.07 ± 1.69 years) and 240 male European controls were examined. Polygenic profiles comprised 39 single nucleotide polymorphisms and were analysed using unweighted and weighted total genotype scores (TGSs; TWGSs). There were significant differences in polygenic profiles between groups, whereby U17-23 players had more genetic variants associated with later maturity compared to U12-16 players (TGS, p = 0.010; TWGS, p = 0.024) and controls (TGS, p = 0.038; TWGS, p = 0.020). More specifically, U17-23 players had over two-times the odds of possessing >36 later-maturing alleles than <30 compared to U12-16 players (odds ratio (OR) = 2.84) and controls (OR = 2.08). These results suggest there was a greater proportion of relatively later-maturing players as maturation plateaus towards adulthood, which may be explained by the 'underdog hypothesis'. This study provides the first known molecular evidence that supports the notion that a maturity selection bias exists within male academy football.

The PPARGC1A Gly482Ser polymorphism is associated with elite long-distance running performance.

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.

Collagen Gene Polymorphisms Previously Associated with Resistance to Soft-Tissue Injury Are More Common in Competitive Runners Than Nonathletes.

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.

Gene variants previously associated with reduced soft tissue injury risk: Part 1 - independent associations with elite status in rugby.

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 Χ2 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.

Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status.

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.

Genetic associations with technical capabilities in English academy football players: a preliminary study.

BACKGROUND: Technical capabilities have significant discriminative and prognostic power in youth football. Although, many factors influence technical performance, no research has explored the genetic contribution. As such, the purpose of this study was to examine the association of several single nucleotide polymorphisms (SNPs) with technical assessments in youth football players. METHODS: Fifty-three male under-13 to under-18 outfield football players from two Category 3 English academies were genotyped for eight SNPs. Objective and subjective technical performance scores in dribbling, passing, and shooting were collated. Simple linear regression was used to analyse individual SNP associations each variable, whereas both unweighted and weighted total genotype scores (TGSs; TWGSs) were computed to measure the combined influence of all SNPs. RESULTS: In isolation, the ADBR2 (rs1042714) C allele, BDNF (rs6265) C/C genotype, DBH (rs1611115) C/C genotype, and DRD1 (rs4532) C allele were associated with superior (8-10%) objective dribbling and/or shooting performance. The TGSs and/or TWGSs were significantly correlated with each technical assessment (except subjective passing), explaining up to 36% and 40% of the variance in the objective and subjective assessments, respectively. CONCLUSIONS: The results of this study suggest inter-individual genetic variation may influence the technical capabilities of youth football players and proposes several candidate SNPs that warrant further investigation.

Gene variants previously associated with reduced soft-tissue injury risk: Part 2 - Polygenic associations with elite status in Rugby.

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.HighlightsElite 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.

Genetic Variations between Youth and Professional Development Phase English Academy Football Players.

The purpose of this study was to examine differences in the genotype frequency distribution of thirty-three single nucleotide variants (SNVs) between youth development phase (YDP) and professional development phase (PDP) academy football players. One hundred and sixty-six male football players from two Category 1 and Category 3 English academies were examined within their specific age phase: YDP (n = 92; aged 13.84 ± 1.63 years) and PDP (n = 74; aged 18.09 ± 1.51 years). Fisher's exact tests were used to compare individual genotype frequencies, whereas unweighted and weighted total genotype scores (TGS; TWGS) were computed to assess differences in polygenic profiles. In isolation, the IL6 (rs1800795) G allele was overrepresented in PDP players (90.5%) compared to YDP players (77.2%; p = 0.023), whereby PDP players had nearly three times the odds of possessing a G allele (OR = 2.83, 95% CI: 1.13-7.09). The TGS (p = 0.001) and TWGS (p < 0.001) were significant, but poor, in distinguishing YDP and PDP players (AUC = 0.643-0.694), with PDP players exhibiting an overall more power-orientated polygenic profile. If validated in larger independent youth football cohorts, these findings may have important implications for future studies examining genetic associations in youth football.

Polygenic Models Partially Predict Muscle Size and Strength but Not Low Muscle Mass in Older Women.

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.

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes.

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.

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.

An investigation into the association of bone characteristics and body composition with stress fracture in athletes.

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/cm2, women 1.19±0.09 g/cm2), 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.

Genetic association research in football: A systematic review.

Genetic variation is responsible for a large amount of the inter-individual performance disparities seen in sport. As such, in the last ten years genetic association studies have become more common; with one of the most frequently researched sports being football. However, the progress and methodological rigour of genetic association research in football is yet to be evaluated. Therefore, the aim of this paper was to identify and evaluate all genetic association studies involving football players and outline where and how future research should be directed. Firstly, a systematic search was conducted in the Pubmed and SPORTDiscus databases, which identified 80 eligible studies. Progression analysis revealed that 103 distinct genes have been investigated across multiple disciplines; however, research has predominately focused on the association of the ACTN3 or ACE gene. Furthermore, 55% of the total studies have been published within the last four years; showcasing that genetic association research in football is increasing at a substantial rate. However, there are several methodological inconsistencies which hinder research implications, such as; inadequate description or omission of ethnicity and on-field positions. Furthermore, there is a limited amount of research on several key areas crucial to footballing performance, in particular; psychological related traits. Moving forward, improved research designs, larger sample sizes, and the utilisation of genome-wide and polygenic profiling approaches are recommended. Finally, we introduce the Football Gene Project, which aims to address several of these limitations and ultimately facilitate greater individualised athlete development within football.

The association of the ACTN3 R577X and ACE I/D polymorphisms with athlete status in football: a systematic review and meta-analysis.

The aim of this review was to assess the association of ACTN3 R577X and ACE I/D polymorphisms with athlete status in football and determine which allele and/or genotypes are most likely to influence this phenotype via a meta-analysis. A comprehensive search identified 17 ACTN3 and 19 ACE studies. Significant associations were shown between the presence of the ACTN3 R allele and professional footballer status (OR = 1.35, 95% CI: 1.18-1.53) and the ACE D allele and youth footballers (OR = 1.18, 95% CI: 1.01-1.38). More specifically, the ACTN3 RR genotype (OR = 1.48, 95% CI: 1.23-1.77) and ACE DD genotype (OR = 1.29, 95% CI: 1.02-1.63) exhibited the strongest associations, respectively. These findings may be explained by the association of the ACTN3 RR genotype and ACE DD genotype with power-orientated phenotypes and the relative contribution of power-orientated phenotypes to success in football. As such, the results of this review provide further evidence that individual genetic variation may contribute towards athlete status and can differentiate athletes of different competitive playing statuses in a homogenous team-sport cohort. Moreover, the ACTN3 R577X and ACE I/D polymorphisms are likely (albeit relatively minor) contributing factors that influence athlete status in football.

The Association of Multiple Gene Variants with Ageing Skeletal Muscle Phenotypes in Elderly Women.

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 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 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.