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    Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes

    Antrobus, Mark R, Brazier, Jon, Callus, Peter C, Herbert, Adam J, Stebbings, Georgina K ORCID logoORCID: https://orcid.org/0000-0003-0706-2864, 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 ORCID logoORCID: https://orcid.org/0000-0002-8052-8184 (2022) Concussion-Associated Polygenic Profiles of Elite Male Rugby Athletes. Genes, 13 (5). 820.

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    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 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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