1261 Discovery of Single Nucleotide Polymorphisms Associated With Functional Outcomes After Traumatic Brain Injury: An All of Us Research Database Analysis

INTRODUCTION: Functional outcomes following traumatic brain injury (TBI) often vary widely, making prognosis and subsequent therapy difficult. Accordingly, there has been increased interest in understanding how genetic predisposition may influence outcomes and allow for better risk stratification and precision rehabilitation. METHODS: Using All of Us Research Program, patients with a diagnosis of “traumatic brain injury” per ICD-9/10 codes were included for analysis (n = 6,761). Ordinal logistic regression analyzed 39 SNPs in relation to patients’ self-reported ability to perform everyday activities. Coarsened exact matching (CEM) was used to create a matching cohort of patients without and without the given SNP being analyzed. Bonferroni correction was used to account for multiple hypothesis testing. RESULTS: The mean age was 50.6 (± 17.5) years. The majority of patients were female (59.7%), white (61.5%), non-Hispanic (80%), and unemployed (57.5%). Of 39 SNPs previously implicated in TBI, two had a significant association with TBI patients’ ability to perform everyday activities after multiple hypothesis correction. Specifically, ACE gene rs4343 (OR 1.56, 95% CI 1.21-2.01, P < 0.001) and FOXP2 gene rs71149745 (OR 1.56, 95% CI 1.20-2.03, P = 0.001) were associated with being able to do everyday activities. Literature review revealed that ACE gene rs4343 has been implicated in migraine severity while FOXP2 gene rs71149745 has been implicated in language development and depression, suggesting biologic plausibility. CONCLUSIONS: We identified two SNPs that are associated with TBI patients’ ability to perform everyday activities. Further analysis of how these SNPs interact to influence patient outcomes following TBI may contribute to better prognostic tools for more personalized and targeted patient therapy.