Traumatic brain injury (TBI) is a leading cause of mortality, and the leading cause of neurodisability, globally. Less than 50% of the substantial inter-individual variability in outcome in TBI is explained by classical covariates. We know that genetic variation modulates TBI outcome, but past studies have been small with limited gene targets. The Genetic Associations in Neurotrauma (GAIN) Consortium will draw on large studies funded as part of the International Traumatic Brain Injury Research (InTBIR) initiative, supplemented with cohorts from past high-quality studies, to generate a well-characterized sample of patients with blood banked for genetic analysis. Our initial sample consists of over 7000 patients from the CENTER-TBI and TRACK-TBI studies, supplemented by historical datasets and past trials, but the potential exists to expand this to over 10,000 patients. We will use this substantial resource to conduct the first ever genome-wide association study (GWAS) in TBI, aiming to identify biological mechanisms that modulate response and recovery from injury. GAIN will also draw on the expertise of genetics consortia in other diseases, to integrate rigorous phenotype harmonization with state-of-the-art genotyping and analysis. Our outputs could transform our understanding of TBI biology, and provide future research dividends. Discovering these variants could characterise novel disease mechanisms, improve prognostic precision, identify new therapeutic targets, and allow patient stratification for precision medicine approaches. GAIN will also remain open to new partners, and foster the collection of DNA as part of any planned or future high quality observational trial or interventional study, since an expanding collection of DNA samples and well characterised phenotype could bear substantial scientific and clinical dividends.
