Genetic factors in traumatic brain injury.

Outcome after a traumatic brain injury (TBI) can be quite variable and unpredictable. This suggests factors other than injury severity play important roles in outcome. Host genotype might be one such factor. This chapter reviews key concepts important to understanding genetic influences on the response to and recovery from TBI. As an organizing framework, four broad contexts in which individual differences could play an important role in outcome after trauma are presented: (1) genes that may modulate injury extent and serve to augment or dampen the impact of a given "dose" of neurotrauma, (2) genes that may play a role in repair and recovery from injury and thus impact the trajectory of recovery and ultimate functional outcome, (3) genes modulating preinjury traits (e.g., resilience), or cognition (cognitive reserve), (4) interactions between genetic vulnerabilities to neurobehavioral disorders and neurotrauma (i.e., role of comorbidities). Each of these four broad categories involve multiple components and thus are under complex polygenic control suggesting that functional outcome following TBI is best viewed as a complex polygenic phenotype. Although the individual contribution of a given allele might be small, the effects of multiple alleles could be quite significant.