Genetic Risk Score Predicts TBI Outcomes
A genetic risk score could help predict a patient’s quality of life after a traumatic brain injury (TBI), said researchers. One day, physicians could have a simple method to forecast a patient’s recovery and personalize therapy to maximize quality of life.
“Gene pathways can influence all of our biologic functions and risk for many health outcomes,” said Mark Linsenmeyer, MD, a resident physician at the University of Pittsburgh Medical Center. “Each person has a unique inherited genetic code. By studying one gene pathway in a large group of people with the same disease or health problem, we hope to unlock clues to why some people have different outcomes than others. This knowledge may be used to help physicians make the best treatment choice for each person.”
Dr. Linsenmeyer and colleagues set out to investigate how genes that affect the brain’s dopamine pathways could predict recovery in people with moderate-to-severe TBI. The team recruited 94 adults with TBI from a level-1 trauma center. They focused on the following five genes in the dopamine pathways: COMT rs4680, VMAT2 rs363226, DRD2 rs6279, ANKK1 Taq1a, and MAOA VNTR. They defined which risk genotypes were associated with lower average scores on surveys filled out by patients with TBI to describe their overall quality of life at six and 12 months after their injuries.
The researchers analyzed how individual variants of each of these five genes could affect patients’ quality of life, and then generated a weighted gene risk score as a measure to reflect cumulative risk represented by all genotypes included in the score. Based on available literature about dopamine pathway genetics, they predicted that their gene risk score calculation tool should be specific to a patient’s sex.
Before they calculated gene risk scores, the research team noticed that only COMT could significantly predict quality of life for a subset of patients six months after their injuries. After generating sex-specific gene risk scores, they found that variants of all five genes on the dopamine pathway could meaningfully contribute to a gene risk score that was highly predictive of quality of life after six months for patients of both sexes with TBI, and also predictive of quality of life after one year for women.