Research Reports - A dopamine pathway gene risk score for cognitive recovery following traumatic brain injury

J Head Trauma Rehabil. 2015 Nov 17. [Epub ahead of print]

Myrga JM(1), Failla MD, Ricker JH, Dixon CE, Conley YP, Arenth PM, Wagner AK.

OBJECTIVES: With evidence of sexual dimorphism involving the dopamine
(DA)-pathway, and the importance of DA pathways in traumatic brain injury (TBI)
recovery, we hypothesized that sex × DA-gene interactions may influence cognition
PARTICIPANTS: Adult survivors of severe TBI (n = 193) consecutively recruited
from a level 1 trauma center.
DESIGN: 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,
semiweighted, and weighted gene risk score (GRS) approaches.
MAIN MEASURES: A cognitive composite score generated from 8 standardized
neuropsychological tests targeting multiple cognitive domains.
RESULTS: A significant sex × gene interaction was observed at 6 and 12 months for
ANKK1 rs1800497 (6M: P = .002, 12M: P = .001) and COMT rs4680 (6M: P = .048; 12M:
P = .004); DRD2 rs6279 (P = .001) and VMAT rs363226 (P = .043) genotypes were
independently associated with cognition at 6 months, with trends for a sex × 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: R = 0.344 (6 months); R = 0.441 (12
months), significantly increasing the variance captured from the base prediction
CONCLUSIONS: 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. 

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