Model System:

TBI

Reference Type:

Journal

Accession No.:

J75672

Journal:


Journal of Head Trauma Rehabilitation

Year, Volume, Issue, Page(s):

, 31, 5, E15-E29

Publication Website:

Abstract:

Study investigated sexual dimorphism within the dopamine (DA) gene pathway that may influence cognitive outcomes following traumatic brain injury (TBI). Dopamine is critical for attention, memory, and planning, and DA deficiencies lead to cognitive deficits. Participants were 193 adult survivors of severe TBI recruited from a level 1 trauma center. Risk allele assignments were made for multiple DA pathway genes using a sex-specific stratified approach. Genetic risk alleles, and their impacts on cognition, were assessed at 6 and 12 months postinjury using unweighted, semi-weighted, and weighted gene risk score (GRS) approaches. A cognitive composite score was generated from 8 standardized neuropsychological tests targeting multiple cognitive domains. A significant sex-by-gene interaction was observed at 6 and 12 months for ANKK1 rs1800497 and COMT rs4680; DRD2 rs6279 and VMAT rs363226 genotypes were independently associated with cognition at 6 months, with trends for a sex-by-gene interaction at 12 months. All GRS methods were significant predictors of cognitive performance in multivariable models. Weighted GRS multivariate models captured the greatest variance in cognition, significantly increasing the variance captured from the base prediction models. Result suggest that a sex-specific DA-pathway GRS may be a valuable tool when predicting cognitive recovery post-TBI. Future work should validate these findings and explore how DA-pathway genetics may guide therapeutic intervention.

Author(s):


Myrga, John M., Failla, Michelle D., Ricker, Joseph H., Dixon, C. Edward, Conley, Yvette P., Arenth, Patricia M., Wagner, Amy K.

Participating Centers: