A Systematic Review of the Genetic Predisposition to Injury in Football

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.