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Genetic polymorphisms associated with the risk of concussion in 1056 college athletes: a multicentre prospective cohort study
  1. Thomas Roland Terrell1,2,
  2. Ruth Abramson3,
  3. Jeffery T Barth4,
  4. Ellen Bennett5,
  5. Robert C Cantu6,7,
  6. Richard Sloane8,
  7. Daniel T Laskowitz9,10,
  8. David M Erlanger11,12,
  9. Douglas McKeag13,
  10. Gregory Nichols14,
  11. Verle Valentine15,
  12. Leslie Galloway16,17
  1. 1 Department of Family Medicine, Primary Care Sports Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee, USA
  2. 2 Family Medicine and Sports Medicine Center, Covenant Medical Group, Knoxville, Tennessee, USA
  3. 3 Department of Neuropsychiatry and Behavioral Sciences, University of South Carolina School of Medicine, Columbia, South Carolina, USA
  4. 4 Department of Psychiatry and Neurobehavioral Sciences, Brain Injury and Sports Concussion Institute, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  5. 5 Department of Neurology, Duke University Medical Center, Durham, North Carolina, USA
  6. 6 Boston University School of Medicine, Boston, Massachusetts, USA
  7. 7 Center for the Study of Chronic Traumatic Encephalopathy, Boston, Massachusetts, USA
  8. 8 Duke University Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, USA
  9. 9 Neurobiology and Anesthesiology, Duke University Hospital, Durham, NC, USA
  10. 10 Neurology and Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA
  11. 11 Rusk Institute of Rehabilitation Medicine, New York, USA
  12. 12 University Langone Medical Center, New York, USA
  13. 13 Department of Family Medicine, University of Oregon Health Science Center, Portland, Oregon, USA
  14. 14 Oak Ridge Associated Universities, Oak Ridge, Tennessee, USA
  15. 15 Sanford Orthopaedics and Sports Medicine, Sanford Health Care, Sioux Falls, South Dakota, USA
  16. 16 Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, Tennessee, USA
  17. 17 Environmental Sciences Division, Toxicology and Risk Analysis, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA
  1. Correspondence to Thomas Roland Terrell, Family Medicine and Sports Medicine Center, Covenant Medical Group, 110 Executive Park Drive, Clinton, TN 37716; tterrell20{at}


Background/aim To evaluate the association of genetic polymorphisms APOE, APOE G-219T promoter, microtubule associated protein(MAPT)/tau exon 6 Ser53Pro, MAPT/tau Hist47Tyr, IL-6572 G/C and IL-6R Asp358Ala with the risk of concussion in college athletes.

Methods A 23-centre prospective cohort study of 1056 college athletes with genotyping was completed between August 2003 and December 2012. All athletes completed baseline medical and concussion questionnaires, and post-concussion data were collected for athletes with a documented concussion.

Results The study cohort consisted of 1056 athletes of mean±SD age 19.7±1.5 years, 89.3% male, 59.4% Caucasian, 35.0% African-American, 5.6% other race. The athletes participated in American football, soccer, basketball, softball, men’s wrestling and club rugby. A total of 133 (12.1% prevalence) concussions occurred during an average surveillance of 3 years per athlete. We observed a significant positive association between IL-6R CC (p=0.001) and a negative association between APOE4 (p=0.03) and the risk of concussion. Unadjusted and adjusted logistic regression analysis showed a significant association between IL-6R CC and concussion (OR 3.48; 95% CI 1.58 to 7.65; p=0.002) and between the APOE4 allele and concussion (OR 0.61; 95% CI 0.38 to 0.96; p=0.04), which persisted after adjustment for confounders.

Conclusions IL-6R CC was associated with a three times greater concussion risk and APOE4 with a 40% lower risk.

  • IL-6 gene
  • APOE4
  • genotype
  • sport
  • traumatic brain injury

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  • Contributors Each of the authors in this study contributed appropriately to the research study described in the manuscript and have each reviewed the manuscript and had an opportunity to make editorial changes.

  • Funding Grant funding was provided by the National Operating Committee on Standards for Athletic Equipment (NOCSAE), American Medical Society of Sports Medicine (AMSSM), and Physicians Medical Education and Research Foundation of the University of Tennessee Medical Center (PMERF). The opinions expressed by the authors are not those of these organizations, but are rather our own.

  • Competing interests RCC is a paid consultant to the NFL Head Neck and Spine Committee, NOCSAE, Concussion Legacy Foundation, receives royalties from book publications and compensation for expert legal opinion.

  • Ethics approval University of Tennessee Graduate School of Medicine IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Any unpublished data are available from the primary author.