Skip to main content
SpringerLink
Log in

Genetics in Concussion

  • Chapter
  • First Online:
Concussions in Athletics

  • 749 Accesses

Abstract

Due to the heterogenous nature of concussion, also known as mild traumatic brain injury (mTBI), it can be assumed that genetics may play a role. The various risk factors associated with sustaining an injury, as well as the various recovery patterns after injury, are thought to have an underlying genetic component that may contribute. The use of genetics as a field in neurologic research has been steadily growing; however, its use in concussion and mild traumatic brain injury is still in its infancy. This chapter aims to explore the current findings on the following: (a) risk of sustaining an injury; and (b) recovery after injury in athletic and military populations. The studies included in this chapter represent the use of a wide variety of single-nucleotide polymorphisms (SNPs) that are examined at a relatively low frequency. Therefore, at this time, it is challenging to make any conclusive statements regarding the role of genetics in concussion and future work needs to expand on these studies in more comprehensive and systemic ways.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. McCrory P, Meeuwisse W, Dvořák J, Aubry M, Bailes J, Broglio S, et al. Consensus statement on concussion in sport-the 5th international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med. 2017;51:838–47.

    PubMed  Google Scholar 

  2. Ellis MJ, Leiter J, Hall T, McDonald PJ, Sawyer S, Silver N, et al. Neuroimaging findings in pediatric sports-related concussion. J Neurosurg Pediatr. 2015;16:241–7.

    Article  PubMed  Google Scholar 

  3. Lovell MR, Collins MW, Iverson GL, Johnston KM, Bradley JP. Grade 1 or “ding” concussions in high school athletes. Am J Sports Med. 2004;32:47–54.

    Article  PubMed  Google Scholar 

  4. Graham R, Rivara FP, Ford MA, Spicer CM, Committee on Sports-Related Concussions in Youth; Board on Children, Youth and Families, et al. Treatment and management of prolonged symptoms and post-concussion syndrome [Internet]. In: Sports-related concussions in youth: improving the science, changing the culture. Washington, DC: National Academies Press; 2014. [cited 2020 Jan 20]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK185342/.

    Google Scholar 

  5. Scopaz KA, Hatzenbuehler JR. Risk modifiers for concussion and prolonged recovery. Sports Health. 2013;5:537–41.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Iverson GL, Gardner AJ, Terry DP, Ponsford JL, Sills AK, Broshek DK, et al. Predictors of clinical recovery from concussion: a systematic review. Br J Sports Med. 2017;51:941–8.

    Article  PubMed  Google Scholar 

  7. Nikolac Perkovic M, Pivac N. Genetic markers of Alzheimer’s disease. Adv Exp Med Biol. 2019;1192:27–52.

    Article  CAS  PubMed  Google Scholar 

  8. Kim CY, Alcalay RN. Genetic forms of Parkinson’s disease. Semin Neurol. 2017;37:135–46.

    Article  PubMed  Google Scholar 

  9. Mejzini R, Flynn LL, Pitout IL, Fletcher S, Wilton SD, Akkari PA. ALS genetics, mechanisms, and therapeutics: where are we now? Front Neurosci. 2019;13:1310. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909825/.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bennett ER, Reuter-Rice K, Laskowitz DT. Genetic influences in traumatic brain injury. In: Laskowitz D, Grant G, editors. Translational research in traumatic brain injury [internet]. Boca Raton: CRC Press/Taylor and Francis Group; 2016. Available from: http://www.ncbi.nlm.nih.gov/books/NBK326717/.

    Google Scholar 

  11. Mahley RW. Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism. Arterioscler Thromb Vasc Biol. 2016;36:1305–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Weisgraber KH, Rall SC, Mahley RW. Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J Biol Chem. 1981;256:9077–83.

    Article  CAS  PubMed  Google Scholar 

  13. Bekris LM, Millard SP, Galloway NM, Vuletic S, Albers JJ, Li G, et al. Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels. J Alzheimers Dis. 2008;13:255–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dretsch MN, Williams K, Emmerich T, Crynen G, Ait-Ghezala G, Chaytow H, et al. Brain-derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress. Brain Behav. 2016;6:e00392. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834940/.

    Article  PubMed  Google Scholar 

  15. Dretsch MN, Silverberg N, Gardner AJ, Panenka WJ, Emmerich T, Crynen G, et al. Genetics and other risk factors for past concussions in active-duty soldiers. J Neurotrauma. 2017;34:869–75.

    Article  PubMed  Google Scholar 

  16. Kristman VL, Tator CH, Kreiger N, Richards D, Mainwaring L, Jaglal S, et al. Does the apolipoprotein epsilon 4 allele predispose varsity athletes to concussion? A prospective cohort study. Clin J Sport Med. 2008;18:322–8.

    Article  PubMed  Google Scholar 

  17. Terrell TR, Bostick RM, Abramson R, Xie D, Barfield W, Cantu R, et al. APOE, APOE promoter, and tau genotypes and risk for concussion in college athletes. Clin J Sport Med. 2008;18:10–7.

    Article  PubMed  Google Scholar 

  18. Tierney RT, Mansell JL, Higgins M, McDevitt JK, Toone N, Gaughan JP, et al. Apolipoprotein E genotype and concussion in college athletes. Clin J Sport Med. 2010;20:464–8.

    Article  PubMed  Google Scholar 

  19. Abrahams S, Mc Fie S, Patricios J, Suter J, Posthumus M, September AV. An association between polymorphisms within the APOE gene and concussion aetiology in rugby union players. J Sci Med Sport. 2018;21(2):117–22.

    Article  PubMed  Google Scholar 

  20. Cochrane GD, Sundman MH, Hall EE, Kostek MC, Patel K, Barnes KP, et al. Genetics influence neurocognitive performance at baseline but not concussion history in collegiate student-athletes. Clin J Sport Med. 2018;28(2):125–9.

    Article  PubMed  Google Scholar 

  21. Walter A, Herrold AA, Gallagher VT, Lee R, Scaramuzzo M, Bream T, et al. KIAA0319 genotype predicts the number of past concussions in a division I football team: a pilot study. J Neurotrauma. 2019;36:1115–24.

    Article  PubMed  Google Scholar 

  22. Terrell TR, Abramson R, Barth JT, Bennett E, Cantu RC, Sloane R, et al. Genetic polymorphisms associated with the risk of concussion in 1056 college athletes: a multicentre prospective cohort study. Br J Sports Med. 2018;52:192–8.

    Article  PubMed  Google Scholar 

  23. Moran LM, Taylor HG, Ganesalingam K, Gastier-Foster JM, Frick J, Bangert B, et al. Apolipoprotein E4 as a predictor of outcomes in pediatric mild traumatic brain injury. J Neurotrauma. 2009;26:1489–95.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Merritt VC, Rabinowitz AR, Arnett PA. The influence of the apolipoprotein E (APOE) gene on subacute post-concussion neurocognitive performance in college athletes. Arch Clin Neuropsychol. 2018;33:36–46.

    Article  PubMed  Google Scholar 

  25. Merritt VC, Ukueberuwa DM, Arnett PA. Relationship between the apolipoprotein E gene and headache following sports-related concussion. J Clin Exp Neuropsychol. 2016;38:941–9.

    Article  PubMed  Google Scholar 

  26. Merritt VC, Arnett PA. Apolipoprotein E (APOE) ϵ4 allele is associated with increased symptom reporting following sports concussion. J Int Neuropsychol Soc. 2016;22:89–94.

    Article  PubMed  Google Scholar 

  27. Yoshii A, Constantine-Paton M. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 2010;70:304–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Figurov A, Pozzo-Miller LD, Olafsson P, Wang T, Lu B. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature. 1996;381:706–9.

    Article  CAS  PubMed  Google Scholar 

  29. Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112:257–69.

    Article  CAS  PubMed  Google Scholar 

  30. Gurevich EV, Gainetdinov RR, Gurevich VV. G protein-coupled receptor kinases as regulators of dopamine receptor functions. Pharmacol Res. 2016;111:1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bunzow JR, Van Tol HH, Grandy DK, Albert P, Salon J, Christie M, et al. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature. 1988;336:783–7.

    Article  CAS  PubMed  Google Scholar 

  32. Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, et al. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature. 1991;350:610–4.

    Article  PubMed  Google Scholar 

  33. Hehar H, Yeates K, Kolb B, Esser MJ, Mychasiuk R. Impulsivity and concussion in juvenile rats: examining molecular and structural aspects of the frontostriatal pathway. PLoS One. 2015;10:e0139842.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Garris PA, Collins LB, Jones SR, Wightman RM. Evoked extracellular dopamine in vivo in the medial prefrontal cortex. J Neurochem. 1993;61:637–47.

    Article  CAS  PubMed  Google Scholar 

  35. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet. 2004;75:807–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S, et al. Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J. 1987;6:2939–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kamimura D, Ishihara K, Hirano T. IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol. 2003;149:1–38.

    CAS  PubMed  Google Scholar 

  38. Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M. Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology. 2001;40:656–61.

    Article  CAS  PubMed  Google Scholar 

  39. Yang SH, Gangidine M, Pritts TA, Goodman MD, Lentsch AB. Interleukin 6 mediates neuroinflammation and motor coordination deficits after mild traumatic brain injury and brief hypoxia in mice. Shock. 2013;40:471–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mc Fie S, Abrahams S, Patricios J, Suter J, Posthumus M, September AV. Inflammatory and apoptotic signalling pathways and concussion severity: a genetic association study. J Sports Sci. 2018;36:2226–34.

    Article  PubMed  Google Scholar 

  41. Barbier P, Zejneli O, Martinho M, Lasorsa A, Belle V, Smet-Nocca C, et al. Role of tau as a microtubule-associated protein: structural and functional aspects. Front Aging Neurosci. 2019;11:204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Abrahams S, Mc Fie S, Patricios J, Suter J, September AV, Posthumus M. Toxic TAU: the TAU gene polymorphisms associate with concussion history in rugby union players. J Sci Med Sport. 2019;22:22–8.

    Article  PubMed  Google Scholar 

  43. Paracchini S, Thomas A, Castro S, Lai C, Paramasivam M, Wang Y, et al. The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration. Hum Mol Genet. 2006;15:1659–66.

    Article  CAS  PubMed  Google Scholar 

  44. Francks C, Paracchini S, Smith SD, Richardson AJ, Scerri TS, Cardon LR, et al. A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States. Am J Hum Genet. 2004;75:1046–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Madura SA, McDevitt JK, Tierney RT, Mansell JL, Hayes DJ, Gaughan JP, et al. Genetic variation in SLC17A7 promoter associated with response to sport-related concussions. Brain Inj. 2016;30:908–13.

    Article  PubMed  Google Scholar 

  46. McDevitt J. CNS voltage-gated calcium channel gene variation and prolonged recovery following sport-related concussion. Orthop J Sports Med. 2016;4:2325967116S00074. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901914/.

    Article  PubMed Central  Google Scholar 

  47. McDevitt JK, Tierney RT, Mansell JL, Driban JB, Higgins M, Toone N, et al. Neuronal structural protein polymorphism and concussion in college athletes. Brain Inj. 2011;25:1108–13.

    Article  PubMed  Google Scholar 

  48. McDevitt J, Tierney RT, Phillips J, Gaughan JP, Torg JS, Krynetskiy E. Association between GRIN2A promoter polymorphism and recovery from concussion. Brain Inj. 2015;29:1674–81.

    Article  PubMed  Google Scholar 

  49. Szabo MC, Soo KS, Zlotnik A, Schall TJ. Chemokine class differences in binding to the Duffy antigen-erythrocyte chemokine receptor. J Biol Chem. 1995;270:25348–51.

    Article  CAS  PubMed  Google Scholar 

  50. Gardner L, Patterson AM, Ashton BA, Stone MA, Middleton J. The human Duffy antigen binds selected inflammatory but not homeostatic chemokines. Biochem Biophys Res Commun. 2004;321:306–12.

    Article  CAS  PubMed  Google Scholar 

  51. Minten C, Alt C, Gentner M, Frei E, Deutsch U, Lyck R, et al. DARC shuttles inflammatory chemokines across the blood-brain barrier during autoimmune central nervous system inflammation. Brain. 2014;137:1454–69.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Kraus WL, Hottiger MO. PARP-1 and gene regulation: progress and puzzles. Mol Asp Med. 2013;34:1109–23.

    Article  CAS  Google Scholar 

  53. Virág L, Robaszkiewicz A, Rodriguez-Vargas JM, Oliver FJ. Poly(ADP-ribose) signaling in cell death. Mol Asp Med. 2013;34:1153–67.

    Article  CAS  Google Scholar 

  54. Markett S, de Reus MA, Reuter M, Montag C, Weber B, Schoene-Bake J-C, et al. Serotonin and the Brain’s Rich Club-Association between molecular genetic variation on the TPH2 gene and the structural connectome. Cereb Cortex. 2017;27:2166–74.

    PubMed  Google Scholar 

  55. Walther DJ, Bader M. A unique central tryptophan hydroxylase isoform. Biochem Pharmacol. 2003;66:1673–80.

    Article  CAS  PubMed  Google Scholar 

  56. Dewilde S, Kiger L, Burmester T, Hankeln T, Baudin-Creuza V, Aerts T, et al. Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. J Biol Chem. 2001;276:38949–55.

    Article  CAS  PubMed  Google Scholar 

  57. Sun Y, Jin K, Mao XO, Zhu Y, Greenberg DA. Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury. Proc Natl Acad Sci U S A. 2001;98:15306–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Kinesiology, Pennsylvania State University, University Park, PA, USA

    Alexa E. Walter

Authors
  1. Alexa E. Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Kinesiology and Neurosurgery, Pennsylvania State University, University Park, PA, USA

    Semyon M. Slobounov

  2. Department of Orthopedics, Pennsylvania State University, State College, PA, USA

    Wayne J. Sebastianelli

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Walter, A.E. (2021). Genetics in Concussion. In: Slobounov, S.M., Sebastianelli, W.J. (eds) Concussions in Athletics. Springer, Cham. https://doi.org/10.1007/978-3-030-75564-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-75564-5_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-75563-8

  • Online ISBN: 978-3-030-75564-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation