Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program

Large-scale genetic studies of traumatic brain injury (TBI) are lacking; thus, our understanding of the influence of genetic factors on TBI risk and recovery is incomplete. This study aimed to conduct a genome-wide association study (GWAS) of TBI in VA Million Veteran Program (MVP) enrollees. Partic...

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Bibliographic Details
Published in:Molecular psychiatry 2024-01, Vol.29 (1), p.97-111
Main Authors: Merritt, Victoria C., Maihofer, Adam X., Gasperi, Marianna, Chanfreau-Coffinier, Catherine, Stein, Murray B., Panizzon, Matthew S., Hauger, Richard L., Logue, Mark W., Delano-Wood, Lisa, Nievergelt, Caroline M.
Format: Article
Language:English
Subjects:
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Apolipoprotein E
Behavioral Sciences
Biological Psychology
Cognition
Complications
Cortex (cingulate)
Cortex (frontal)
Electronic medical records
Foxp2 protein
Genes
Genetic factors
Genome-wide association studies
Genomes
Genomic analysis
Heritability
Medicine
Medicine & Public Health
Mental disorders
Neurodegenerative diseases
Neurosciences
Nucleus accumbens
Parkinson's disease
Pharmacotherapy
Phenotypes
Polygenic inheritance
Psychiatry
Single-nucleotide polymorphism
Traumatic brain injury
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Summary:Large-scale genetic studies of traumatic brain injury (TBI) are lacking; thus, our understanding of the influence of genetic factors on TBI risk and recovery is incomplete. This study aimed to conduct a genome-wide association study (GWAS) of TBI in VA Million Veteran Program (MVP) enrollees. Participants included a multi-ancestry cohort (European, African, and Hispanic ancestries; N = 304,485; 111,494 TBI cases, 192,991 controls). TBI was assessed using MVP survey data and International Classification of Diseases (ICD) codes from the Veterans Health Administration’s electronic health record. GWAS was performed using logistic regression in PLINK, and meta-analyzed in METAL. FUMA was used for post-GWAS analysis. Genomic structural equation modeling (gSEM) was conducted to investigate underlying genetic associations with TBI, and bivariate MiXeR was used to estimate phenotype specific and shared polygenicity. SNP-based heritability was 0.060 (SE = 0.004, p  = 7.83×10 -66 ). GWAS analysis identified 15 genome-wide significant (GWS) loci at p  
ISSN:1359-4184
1476-5578
1476-5578
DOI:10.1038/s41380-023-02304-8