The genetic association with injury risk in male academy soccer players depends on maturity status

Hall, Elliott; Baumert, Philipp; Larruskain, Jon; Gil, Susana María; Lekue, Josean; Rienzi, Edgardo; Moreno, Sacha; Tannure, Márcio; Murtagh, Conall F.; Ade, Jack; Squires, Paul E.; Orme, Patrick; Anderson, Liam; Brownlee, Thomas E.; Whitworth-Turner, Craig; Morton, James P.; Drust, Barry; Williams, Alun G.; Erskine, Robert M.

doi:10.1111/sms.14077

Cited by 13 publications

(42 citation statements)

References 42 publications

(78 reference statements)

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“…This contrasts with previous associations of physical performance-associated (as opposed to injury-associated) TGSs with elite athlete status of track and field athletes, rowers, cyclists and soccer athletes [38,40,41,44,54]. However, a musculoskeletal soft-tissue injury-associated TGS has recently been shown to differ between injured and non-injured soccer players [55].…”

Section: Discussioncontrasting

confidence: 62%

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

Antrobus

Brazier

Callus

et al. 2022

Genes

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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.

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Section: Discussioncontrasting

confidence: 62%

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

Antrobus

Brazier

Callus

et al. 2022

Genes

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“…It appears, however, that Clarkson et al 2005 [ 29 ] did not study the skeletal muscle isoforms of MYLK and this may explain the discrepancy from the current study where we found no associations to muscular phenotypes with variants of MYLK2 , while there were associations with genetic variants of MYLK1 (smooth muscle isoform) and MYLK3 (myocardial isoform). The MYLK1 rs28497577 GT genotype has recently been shown to associate with slower recovery after knee injury in soccer players [ 57 ]. Intriguingly, polymorphisms of MYLK1 might modulate the pro-inflammatory state of the bowel and nutrient absorption [ 58 ], which are important for the anabolic response in resistance training.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms of muscular fitness in young healthy men

Venckūnas

Degens

2022

PLoS ONE

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The effects of genetic polymorphisms on muscle structure and function remain elusive. The present study tested for possible associations of 16 polymorphisms (across ten candidate genes) with fittness and skeletal muscle phenotypes in 17- to 37-year-old healthy Caucasian male endurance (n = 86), power/strength (n = 75) and team athletes (n = 60), and non-athletes (n = 218). Skeletal muscle function was measured with eight performance tests covering multiple aspects of muscular fitness. Along with body mass and height, the upper arm and limb girths, and maximal oxygen uptake were measured. Genotyping was conducted on DNA extracted from blood. Of the 16 polymorphisms studied, nine (spanning seven candidate genes and four gene families/signalling pathways) were independently associated with at least one skeletal muscle fitness measure (size or function, or both) measure and explained up to 4.1% of its variation. Five of the studied polymorphisms (activin- and adreno-receptors, as well as myosine light chain kinase 1) in a group of one to three combined with body height, age and/or group explained up to 20.4% of the variation of muscle function. ACVR1B (rs2854464) contributed 2.0–3.6% to explain up to 14.6% of limb proximal girths. The G allele (genotypes AG and GG) of the ACVR1B (rs2854464) polymorphism was significantly overrepresented among team (60.4%) and power (62.0%) athletes compared to controls (52.3%) and endurance athletes (39.2%), and G allele was also most consistently/frequently associated with muscle size and power. Overall, the investigated polymorphisms determined up to 4.1% of the variability of muscular fitness in healthy young humans.

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“…Therefore, it has also been speculated that although football players possessing a XX genotype may recover at a faster rate, they are perhaps exposed to an intolerable amount of muscle damage, inhibiting the recovery process [8]. Indeed, several studies found that XX homozygotes sustained more severe injuries or were absent for a greater number of days following injury [23,46,67]. A mechanistic explanation for an increased injury risk in those with the XX variant has been proposed.…”

Section: Discussionmentioning

confidence: 99%

“…The VEGFA (rs2010963) polymorphism was investigated in four studies using independent cohorts. The two studies that reported an association between VEGFA (rs2010963) and injury found associations with ACL ruptures [36,37] and ligament or tendon injuries [23]. The two studies that reported no association between VEGFA (rs2010963) and injury were investigating ACL ruptures [66] and hamstring injuries [33].…”

Section: Discussionmentioning

confidence: 99%

“…More specifically, the XX genotype of ACTN3 (rs1815739) was associated with an increased susceptibility to non-contact muscle injuries [8,46]. Whereas the G allele and TT genotype of ACAN (rs1516797) were associated with increased and decreased susceptibility to ACL injuries, respectively [7,41], whilst the CC genotype of VEGFA (rs2010963) was associated with an increased risk of ACL rupture [36,37] and ligament or tendon injuries [23]. In the only GWAS [68], three additional polymorphisms had a 'suggestive' association (P < 10 -5 with tendinopathy; however, they failed to reach the study's set (P < 10 -7 ) and typical (P < 10 -8 ) genome-wide statistical significance thresholds. )…”

Section: Genetic Variantsmentioning

confidence: 99%

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A Systematic Review of the Genetic Predisposition to Injury in Football

McAuley

Hughes

Tsaprouni

et al. 2022

J. of SCI. IN SPORT AND EXERCISE

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Purpose Synthesise genetic association studies investigating injury involving football players to identify which genetic variants have the most empirical evidence to date. Methods A comprehensive search of the PubMed, SPORTDiscus, and MEDLINE databases until March 11th 2022 identified 34 studies. Inclusion criteria: primary investigations, included football players, examined the association of a genetic variant with injury, and were published in English. Risk of bias was assessed using the Newcastle–Ottawa Scale. A narrative synthesis summarised results. Results There were 33 candidate gene studies and one genome-wide study, with 9642 participants across all studies (range = 43–1311; median = 227). Ninety-nine polymorphisms were assessed within 63 genes. Forty-one polymorphisms were associated with injury once. Three polymorphisms had their specific allelic associations with injury replicated twice in independent cohorts: ACTN3 (rs1815739) XX genotype was associated with an increased susceptibility to non-contact muscle injuries, ACAN (rs1516797) G allele was associated with increased susceptibility to anterior cruciate ligament (ACL) injuries, and VEGFA (rs2010963) CC genotype was associated with an increased susceptibility to ACL and ligament or tendon injuries. However, several methodological issues (e.g., small sample sizes, cohort heterogeneity, and population stratification) are prevalent that limit the reliability and external validity of findings. Conclusion At present, the evidence base supporting the integration of genetic information as a prognostic or diagnosis tool for injury risk in football is weak. Future participation of organisations in international consortia is suggested to combat the current methodological issues and subsequently improve clarity concerning the underlying genetic contribution to injury susceptibility.

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The genetic association with injury risk in male academy soccer players depends on maturity status

Cited by 13 publications

References 42 publications

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

Genetic polymorphisms of muscular fitness in young healthy men

A Systematic Review of the Genetic Predisposition to Injury in Football

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