@article{ref1,
title="A dopamine pathway gene risk score for cognitive recovery following traumatic brain injury: methodological considerations, preliminary findings, and interactions with sex",
journal="Journal of head trauma rehabilitation",
year="2015",
author="Myrga, John M. and Failla, Michelle D. and Ricker, Joseph H. and Dixon, C. Edward and Conley, Yvette P. and Arenth, Patricia M. and Wagner, Amy K.",
volume="31",
number="5",
pages="E15-29",
abstract="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 post-TBI. PARTICIPANTS: Adult survivors of severe TBI (n = 193) consecutively recruited from a level 1 trauma center. <br><br>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. <br><br>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 models. <br><br>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.<p /> <p>Language: en</p>",
language="en",
issn="0885-9701",
doi="10.1097/HTR.0000000000000199",
url="http://dx.doi.org/10.1097/HTR.0000000000000199"
}