title: Multicenter cohort study on association of genotypes with prospective sports concussion: methods, lessons learned, and recommendations.
abstract: BACKGROUND
  Approximately 3.8 million sports related TBIs occur per year. Genetic variation may affect both TBI risk and post-TBI clinical outcome. Limited research has focused on genetic risk for concussion among athletes. We describe the design, methods, and baseline characteristics of this prospective cohort study designed to investigate a potential association between genetic polymorphisms of apolipoprotein E gene, APOE promoter G-219T, and Tau gene exon 6 polymorphisms (Ser53 Pro and Hist47Tyr) with: 1) the risk of prospective concussion; 2) concussion severity; and 3) postconcussion neurocognitive recovery.
  
  
  METHODS
  The prospective cohort study included a final population of 2947 college, high school, and professional athletes. Baseline data collection included a concussion/medical history questionnaire, neuropsychological (NP) testing, and genetic sampling for the genetic polymorphisms. Data collection on new concussions experienced utilized post-concussion history/mental status form, Lovell post-concussion symptom score, Standardized Assessment of Concussion (SAC) and/or the Sports Concussion Assessment Tool (SCAT)-1/SCAT-2, and post-concussion NP testing.
  
  
  RESULTS
  This paper is focused on discussing the important methodological considerations, organizational challenges and lessons learned in the completion of a multi-center prospective cohort study. A total of 3740 subjects enrolled, with a total of 335 concussions experienced.
  
  
  CONCLUSIONS
  Of critical importance to the success of a study of this type is to successfully recruit committed institutions with qualified local study personnel, obtain "buy-in" from study sites, and cultivate strong working relationships with study sites. The use of approved incentives may improve study site recruitment, enhance retention, and enhance compliance with study protocols. Future publications will detail the specific findings of this study. Collaborative research is very likely needed given the nature of this study population.
authors.affiliation: University of Tennessee Graduate School of Medicine, Department of Family Medicine, Knoxville, TN, USA - 20@gmail.com.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Terrell
authors.affiliation: Emory University, School of Public Health, Department of Epidemiology, Atlanta, GA, USA.
authors.forename: Roberd
authors.initials: R
authors.lastname: Bostick
authors.affiliation: Department of Psychiatry and Neuroscience, Center for Study of Sports TBI, Director, Neuropsychology Service, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Barth
authors.affiliation: Duke University Center for the Study of Aging and Human Development, Duke University Medical Center Durham, Durham, NC, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Sloane
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.|Center for the Study of Chronic Traumatic Encephalopathy, Boston, MA, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Cantu
authors.affiliation: Department of Medicine, Neurology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Bennett
authors.affiliation: Oak Ridge National Laboratory, Oak Ridge, TN, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Galloway
authors.affiliation: Department of Medicine, Neurology and Anesthesiology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Laskowitz
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Dave
authors.initials: D
authors.lastname: Erlanger
authors.affiliation: Department of Family Medicine, University of Indiana School of Medicine, Indianapolis, IN, USA.
authors.forename: Doug
authors.initials: D
authors.lastname: McKeag
authors.affiliation: Sanford School of Medicine of the University of South Dakota, Sioux Falls, SD, USA.
authors.forename: Verle
authors.initials: V
authors.lastname: Valentine
authors.affiliation: Sanford Orthopedics and Sports Medicine, Sioux Falls, SD, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Nichols
mesh_terms: D000293:Adolescent; D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D056352:Athletes; D001265:Athletic Injuries / Q000453:epidemiology / Q000235:genetics*; D000070642:Brain Injuries, Traumatic / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D038223:Post-Concussion Syndrome / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D012574:Schools; D013177:Sports; D011795:Surveys and Questionnaires; D014495:Universities; D016875:tau Proteins / Q000235:genetics*
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; C054369:MAPT protein, human; D016875:tau Proteins