Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status

Mark R Antrobus; Jon Brazier; Peter Callus; Adam J Herbert; Georgina K Stebbings; Stephen H Day; Liam P Kilduff; Mark A Bennett; Robert M Erskine; Stuart M Raleigh; Malcolm Collins; Yannis P Pitsiladis; Shane M Heffernan; Alun G Williams

doi:10.1097/JSM.0000000000001030

Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status

Mark R Antrobus, Jon Brazier, Peter Callus, Adam J Herbert, Georgina K Stebbings, Stephen H Day, Liam P Kilduff, Mark A Bennett, Robert M Erskine, Stuart M Raleigh, Malcolm Collins, Yannis P Pitsiladis, Shane M Heffernan, Alun G Williams

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Abstract

Objective: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes. Design: A case-control genetic association study.Setting: Institutional (university). Participants: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men). Interventions: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes.Main Outcome Measure: Elite athlete status with groups compared using χ2 and odds ratio (OR). Results: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P < 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status. Conclusions: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes.

Original language	English
Pages (from-to)	e145-e151
Number of pages	7
Journal	Clinical Journal of Sport Medicine
Volume	33
Issue number	5
Early online date	29 Mar 2022
DOIs	https://doi.org/10.1097/JSM.0000000000001030
Publication status	Published - Sept 2023

Bibliographical note

Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

This document is the author’s post-print version, incorporating any revisions agreed during the peer-review process. Some differences between the published version and this version may remain and you are advised to consult the published version if you wish to cite from it.

Keywords

rugby
genetics
concussion
brain
polymorphism
behavior

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10.1097/JSM.0000000000001030

Post-PrintAccepted author manuscript, 1.66 MBLicence: CC BY-NC

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Antrobus, M. R., Brazier, J., Callus, P., Herbert, A. J., Stebbings, G. K., Day, S. H., Kilduff, L. P., Bennett, M. A., Erskine, R. M., Raleigh, S. M., Collins, M., Pitsiladis, Y. P., Heffernan, S. M., & Williams, A. G. (2023). Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status. Clinical Journal of Sport Medicine, 33(5), e145-e151. https://doi.org/10.1097/JSM.0000000000001030

Antrobus, MR, Brazier, J, Callus, P, Herbert, AJ, Stebbings, GK, Day, SH, Kilduff, LP, Bennett, MA, Erskine, RM, Raleigh, SM, Collins, M, Pitsiladis, YP, Heffernan, SM & Williams, AG 2023, 'Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status', Clinical Journal of Sport Medicine, vol. 33, no. 5, pp. e145-e151. https://doi.org/10.1097/JSM.0000000000001030

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title = "Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status",

abstract = "Objective: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes. Design: A case-control genetic association study.Setting: Institutional (university). Participants: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men). Interventions: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes.Main Outcome Measure: Elite athlete status with groups compared using χ2 and odds ratio (OR). Results: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P < 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status. Conclusions: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes. ",

keywords = "rugby, genetics, concussion, brain, polymorphism, behavior",

author = "Antrobus, {Mark R} and Jon Brazier and Peter Callus and Herbert, {Adam J} and Stebbings, {Georgina K} and Day, {Stephen H} and Kilduff, {Liam P} and Bennett, {Mark A} and Erskine, {Robert M} and Raleigh, {Stuart M} and Malcolm Collins and Pitsiladis, {Yannis P} and Heffernan, {Shane M} and Williams, {Alun G}",

note = "Copyright {\textcopyright} and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders. This document is the author{\textquoteright}s post-print version, incorporating any revisions agreed during the peer-review process. Some differences between the published version and this version may remain and you are advised to consult the published version if you wish to cite from it. ",

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AU - Brazier, Jon

AU - Callus, Peter

AU - Herbert, Adam J

AU - Stebbings, Georgina K

AU - Day, Stephen H

AU - Kilduff, Liam P

AU - Bennett, Mark A

AU - Erskine, Robert M

AU - Raleigh, Stuart M

AU - Collins, Malcolm

AU - Pitsiladis, Yannis P

AU - Heffernan, Shane M

AU - Williams, Alun G

N1 - Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders. This document is the author’s post-print version, incorporating any revisions agreed during the peer-review process. Some differences between the published version and this version may remain and you are advised to consult the published version if you wish to cite from it.

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N2 - Objective: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes. Design: A case-control genetic association study.Setting: Institutional (university). Participants: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men). Interventions: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes.Main Outcome Measure: Elite athlete status with groups compared using χ2 and odds ratio (OR). Results: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P < 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status. Conclusions: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes.

AB - Objective: Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes. Design: A case-control genetic association study.Setting: Institutional (university). Participants: Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men). Interventions: Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes.Main Outcome Measure: Elite athlete status with groups compared using χ2 and odds ratio (OR). Results: The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P < 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status. Conclusions: Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes.

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KW - genetics

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KW - behavior

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JO - Clinical Journal of Sport Medicine

JF - Clinical Journal of Sport Medicine

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Concussion-Associated Gene Variant COMT rs4680 Is Associated With Elite Rugby Athlete Status

Abstract

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