Concussion-associated gene variants in elite rugby

Antrobus, Mark Robert (2021) Concussion-associated gene variants in elite rugby. Doctoral thesis (DPhil), Manchester Metropolitan University.

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Abstract

Elite rugby league and union have some of the highest reported rates of concussion in professional sport due in part to their full-contact high velocity collision-based nature. Concussion is a complex phenotype, influenced by environmental factors and an individual’s genetic predisposition. The overall aim of the current thesis was to investigate genetic risk factors for frequency and severity of concussion within an elite rugby athlete population. 1683 participants, consisting of 668 elite Caucasian male rugby athletes and 1015 non-athlete Caucasian men and women were recruited for this thesis. Genotype data were generated for eight suspected concussion-associated polymorphisms (APOE rs429358, rs7412 and rs405509, ANKK1 rs1800497, BDNF-AS rs6265, COMT rs4680, MAPT rs10445337 and NOS3 rs2070744). Only COMT rs4680 GG genotype was more common in elite rugby athletes than non-athletes (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.04-1.86). The mean number of concussions experienced by athletes was 2.4 (standard deviation 3.1) concussions. The GG genotype of APOE rs405509 (OR = 2.10, 95% CI = 0.58-7.59), GG genotype of BDNF-AS rs6265 (OR = 17.75, 95% CI = 1.96-160.78) and AA genotype of COMT rs4680 (OR = 2.90, 95% CI = 0.84-10.04) were more common in elite rugby athletes with a history of concussion. In addition, the TT genotype of APOE rs405509 was more common in elite rugby athletes with a concussion recovery duration of <10 days (OR = 4.14, 95% CI = 1.14-15.06). Polygenic profile was quantified as a total genotype score, and suggested that elite rugby athletes do not have a more ‘preferable’ concussion-associated polygenic profile than non-athletes. Similarly, concussion-focused TGS algorithms were not effective in discriminating between elite rugby athletes with a history of concussion and those without. The novel findings presented in this thesis support the growing evidence that elite status, as well as incidence, severity and recovery from concussion, could be influenced by an athlete’s genetic predisposition with respect to concussion injury. Nonetheless, genomic information could in the future potentially be used to inform individualised concussion injury management strategies for athletes in possession of risk genotypes.