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A polygenic score (PGS) can capture the cumulative effect of multiple genetic variants, providing a partial explanation for individual differences in recovery times.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study, our primary objective was to investigate the association between a PGS and recovery time following sport- or military activity-related concussion to better understand the genetic influences on recovery and inform personalized treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genome-wide genotyping data from collegiate athletes and military cadets with confirmed sport- or military activity-related concussions were obtained from the CARE Consortium study (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20094659). A genome-wide association study (GWAS) was conducted on the discovery cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009768 samples) to identify single-nucleotide polymorphisms (SNPs) associated with time to return-to-play initiation (RTPi) after concussion using log-logistic accelerated failure time (AFT) models, adjusted for demographic and injury-related factors, and the first five principal components of genetic ancestries. Linkage disequilibrium-clumped SNPs with the lowest\n                      <jats:italic>p<\/jats:italic>\n                      values were selected and further refined using a robust variable selection method under a multivariable AFT model, resulting in the final set of SNPs. The PGS was constructed from this final set of SNPs and validated in an independent validation cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009262 samples) for time to RTPi. The validation was extended to the biologically relevant slow RTPi outcome (\u2265\u200914\u00a0days) using a logistic regression model. We also tested the PGS for association with time to return-to-play (RTP) and slow RTP (\u2265\u200928\u00a0days) as secondary outcomes. A Gene Ontology (GO) enrichment analysis was performed on the selected SNPs to identify relevant biological processes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The PGS was constructed using 49 SNPs. We found that higher PGS was significantly associated with a longer time to RTPi after concussion (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), where each standard deviation increase in the PGS was associated with a 12% longer time to RTPi. The PGS was significantly associated with a slow RTPi recovery (\u2265\u200914\u00a0days), with each standard deviation increase corresponding to an 82% higher odds of delayed recovery (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). No significant associations were observed between PGS and RTP outcomes. GO enrichment analysis highlighted synaptic mechanisms related to organization, signaling, and neuronal repair, which are critical for restoring neural communication during the healing process.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher PGS is significantly associated with longer recovery time after concussion. This finding provides novel genetic insights for developing personalized treatment strategies to reduce the burden of prolonged recovery from concussion injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40279-026-02477-6","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:22:08Z","timestamp":1782814928000},"page":"2583-2595","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polygenic Score Identifies Athletes at Increased Risk for Slower Recovery After Sport-Related Concussion: A Concussion Assessment, Research, and Education (CARE) Consortium Study"],"prefix":"10.1007","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7214-1959","authenticated-orcid":false,"given":"Zhiqi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-2355","authenticated-orcid":false,"given":"Jill L.","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4040-1717","authenticated-orcid":false,"given":"Kelly N. 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Zhang, J.L. Reiter, D. Lai, P.F. Pasquina, J. Ren, and Y. Liu have no relevant financial or non-financial interests to disclose. K.N.H. Nudelman has current research funding from the National Institutes of Health, the Alzheimer\u2019s Association, the Department of Defense, the Michael J. Fox Foundation for Parkinson\u2019s Research, and the National Collegiate Athletic Association. S.P. Broglio has current research funding from the Centers for Disease Control and Prevention; Department of Defense\u2014USA Medical Research Acquisition Activity, and National Collegiate Athletic Association. He has past research funding from the National Institutes of Health; National Athletic Trainers\u2019 Association Foundation; National Football League\/Under Armour\/GE; Simbex; and ElmindA. He has consulted for US Soccer (paid), US Cycling (unpaid), University of Calgary SHRed Concussions external advisory board (unpaid), and is the President of the Concussion in Sport Group (unpaid). He has received compensation for medico-legal litigation, and received speaker honorarium and travel reimbursements for talks given. He is co-author of \u201cBiomechanics of Injury (3rd edition, Human Kinetics),\u201d holds a patents on \u201cBrain Metabolism Monitoring Through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source\u201d (U.S. US 11, 529, 091 B2) and \u201cOrgan Or Tissue Hemodynamic And Metabolic Function Measured Using Super-Continuum Light Sources\u201d (US 12,089,945 B2), and is on the scientific advisory board for C3Logix (stock options). He is\/was on the editorial boards (all unpaid) for Journal of Athletic Training (2015 to present), Concussion (2014 to present), Athletic Training & Sports Health Care (2008 to present), British Journal of Sports Medicine (2008 to 2019). M.A. McCrea reports research funding to the Medical College of Wisconsin from the National Institutes of Health, U.S. Department of Defense, Department of Veterans Affairs, Centers for Disease Control and Prevention, National Football League, National Collegiate Athletic Association, and Abbott Laboratories. He is a clinical consultant to the Green Bay Packers, Milwaukee Brewers, and Milwaukee Bucks. He also reports honoraria and travel support for professional speaking engagements. T.W. McAllister reports current or prior grant support from National Institutes of Health, U.S. Department of Defense, and National Collegiate Athletic Association, as well as textbook royalties from the \u2018Textbook of Traumatic Brain Injury\u2019 from the American Psychiatric Association Publishing, Inc., and is an unpaid member for the concussion Scientific Advisory Committee for the Australian-Rules Football Conference.","order":1,"name":"Ethics","label":"Conflicts of interest\/competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was completed following approval from the respective local Institutional Review Boards and the United States Army Human Research Protection Office. This study was conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Conceptualization: Jie Ren, Yunlong Liu; data curation: Kelly Nudelman; formal analysis: Zhiqi Zhang, Jie Ren; funding acquisition: Thomas McAllister, Michael McCrea, Steven Broglio, Paul Pasquina; methodology: Zhiqi Zhang, Dongbing Lai, Jie Ren, Yunlong Liu; project administration: Jill Reiter, Jie Ren, Yunlong Liu; resources: Kelly Nudelman, Thomas McAllister, Michael McCrea, Steven Broglio, Paul Pasquina; supervision: Jill Reiter, Jie Ren, Yunlong Liu; validation: Zhiqi Zhang, Jie Ren; visualization: Zhiqi Zhang, Jie Ren; writing\u2014original draft: Zhiqi Zhang, Jie Ren; writing\u2014review and editing: all authors. All authors read and approved the final version of the article.","order":3,"name":"Ethics","label":"Authorship contributions","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The genotyping and GWAS data generated in this study were deposited in the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System under the study name: Concussion Assessment, Research and Education (CARE) Consortium. The dataset names and IDs are: CARE1_GWAS_final_n546_Biomarker, ID 17733; and CARE2_GWAS_Biomarker, ID 17972.","order":4,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Declarations"}}]}}