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.

Is testosterone responsible for athletic success in female athletes?

BACKGROUND: The aim of this study was to determine the interrelationship between the resting serum testosterone (T) levels of female athletes from different types of sporting events and their athletic success. METHODS: The study involved 599 Russian international-level female athletes (95 highly elite, 190 elite, and 314 sub-elite; age: 16-35 years) and 298 age-matched female controls. The athlete cohort was stratified into four groups according to event duration, distance, and type of activity: 1) endurance athletes; 2) athletes with mixed activity; 3) speed/strength athletes; 4) sprinters. Athletic success was measured by determining the level of achievement of each athlete. RESULTS: The mean T levels of athletes and controls were 1.65±0.87 and 1.76±0.6 nmol/L (P=0.057 for difference between groups) with ranges of 0.08-5.82 and 0.38-2.83 nmol/L in athletes and controls, respectively. T levels were positively associated with athletic success in sprinters (P=0.0002 adjusted for age) only. Moreover, none of the sub-elite sprinters had T>1.9 nmol/L, while 50% of elite and highly elite sprinters had T>1.9 nmol/L (OR=47.0; P<0.0001). CONCLUSIONS: Our data suggest that the measurement of the serum T levels significantly correlates with athletic success in sprinters but not other types of athletes and in the future may be useful in the prediction of sprinting ability.

Genome-wide association study identifies a locus associated with rotator cuff injury.

Rotator cuff tears are common, especially in the fifth and sixth decades of life, but can also occur in the competitive athlete. Genetic differences may contribute to overall injury risk. Identifying genetic loci associated with rotator cuff injury could shed light on the etiology of this injury. We performed a genome-wide association screen using publically available data from the Research Program in Genes, Environment and Health including 8,357 cases of rotator cuff injury and 94,622 controls. We found rs71404070 to show a genome-wide significant association with rotator cuff injury with p = 2.31x10-8 and an odds ratio of 1.25 per allele. This SNP is located next to cadherin8, which encodes a protein involved in cell adhesion. We also attempted to validate previous gene association studies that had reported a total of 18 SNPs showing a significant association with rotator cuff injury. However, none of the 18 SNPs were validated in our dataset. rs71404070 may be informative in explaining why some individuals are more susceptible to rotator cuff injury than others.

Two Genetic Loci associated with Medial Collateral Ligament Injury.

Medial collateral ligament (MCL) injuries are a common knee injury, especially in competitive athletes. Identifying genetic loci associated with MCL injury could shed light on its etiology. A genome-wide association screen was performed using data from the Research Program in Genes, Environment and Health (RPGEH) including 1 572 cases of MCL injury and 100 931 controls. 2 SNPs (rs80351309 and rs6083471) showed an association with MCL injury at genome-wide significance (p<5×10-8) with moderate effects (odds ratios=2.12 and 1.57, respectively). For rs80351309, the genotypes were imputed with only moderate accuracy, so this SNP should be viewed with caution until its association with MCL injury can be validated. The SNPs rs80351309 and rs6083471 show a statistically significant association with MCL injury. It will be important to replicate this finding in future studies.

Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.

Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleotide polymorphisms (SNPs) associated with either of these injuries with a p-value that was genome-wide significant (p<5x10-8). We found, however, four and three polymorphisms with p-values that were borderline significant (p<10-6) for Achilles tendon injury and ACL rupture, respectively. We then tested SNPs previously reported to be associated with either Achilles tendon injury or ACL rupture. None showed an association in our cohort with a false discovery rate of less than 5%. We obtained, however, moderate to weak evidence for replication in one case; specifically, rs4919510 in MIR608 had a p-value of 5.1x10-3 for association with Achilles tendon injury, corresponding to a 7% chance of false replication. Finally, we tested 2855 SNPs in 90 candidate genes for musculoskeletal injury, but did not find any that showed a significant association below a false discovery rate of 5%. We provide data containing summary statistics for the entire genome, which will be useful for future genetic studies on these injuries.

Correction: Applying Personal Genetic Data to Injury Risk Assessment in Athletes.

[This corrects the article DOI: 10.1371/journal.pone.0122676.].

Applying personal genetic data to injury risk assessment in athletes.

Recent studies have identified genetic markers associated with risk for certain sports-related injuries and performance-related conditions, with the hope that these markers could be used by individual athletes to personalize their training and diet regimens. We found that we could greatly expand the knowledge base of sports genetic information by using published data originally found in health and disease studies. For example, the results from large genome-wide association studies for low bone mineral density in elderly women can be re-purposed for low bone mineral density in young endurance athletes. In total, we found 124 single-nucleotide polymorphisms associated with: anterior cruciate ligament tear, Achilles tendon injury, low bone mineral density and stress fracture, osteoarthritis, vitamin/mineral deficiencies, and sickle cell trait. Of these single nucleotide polymorphisms, 91% have not previously been used in sports genetics. We conducted a pilot program on fourteen triathletes using this expanded knowledge base of genetic variants associated with sports injury. These athletes were genotyped and educated about how their individual genetic make-up affected their personal risk profile during an hour-long personal consultation. Overall, participants were favorable of the program, found it informative, and most acted upon their genetic results. This pilot program shows that recent genetic research provides valuable information to help reduce sports injuries and to optimize nutrition. There are many genetic studies for health and disease that can be mined to provide useful information to athletes about their individual risk for relevant injuries.