Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

Antrobus, Mark R.; Brazier, Jon; Callus, Peter C.; Herbert, Adam J.; Stebbings, Georgina K.; Khanal, Praval; Day, Stephen H.; Kilduff, Liam P.; Bennett, Mark A.; Erskine, Robert M.; Raleigh, Stuart M.; Collins, Malcolm; Pitsiladis, Yannis P.; Heffernan, Shane M. and Williams, Alun G. (2022). Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes. Genes, 13(5), article no. 820.

DOI: https://doi.org/10.3390/genes13050820

Abstract

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 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. 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) G-C 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 to achieve 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 amongst elite athletes.