Format

Send to

Choose Destination
J Neurotrauma. 2020 Feb 5. doi: 10.1089/neu.2019.6866. [Epub ahead of print]

The Cumulative Influence of Inflammatory Response Genetic Variation on Long-Term Neurobehavioral Outcomes following Pediatric Traumatic Brain Injury Relative to Orthopedic Injury: An Exploratory Polygenic Risk Score.

Author information

1
University of Pittsburgh School of Medicine, 12317, Physical Medicine & Rehabilitation, Pittsburgh, Pennsylvania, United States; amery.treble@chp.edu.
2
Cincinnati Children's Hospital Medical Center, Division of Human Genetics, Cincinnati, Ohio, United States; valentina.pilipenko@cchmc.org.
3
Cincinnati Children's Hospital Medical Center, Pediatrics, 3333 Burnet Avenue MLC 4009, Cincinnati, Ohio, United States, 45229-3039; shari.wade@cchmc.org.
4
Cincinnati Children's Hospital Medical Center, 2518, 240 Albert Sabin Way, Cincinnati, Ohio, United States, 45229; anil.jegga@cchmc.org.
5
University of Calgary, Psychology, 2500 University Dr NW, AD 254, Calgary, Alberta, Canada, T2N1N4; kyeates@ucalgary.ca.
6
Research Institute at Nationwide Childrens Hospital, 51711, Pediatrics , Columbus, Ohio, United States; Hudson.Taylor@NationwideChildrens.org.
7
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States; Lisa.Martin@cchmc.org.
8
Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, United States, 45229; Brad.kurowski@cchmc.org.

Abstract

The addition of genetic factors to prognostic models of neurobehavioral recovery following pediatric traumatic brain injury (TBI) may account for unexplained heterogeneity in outcomes. The present study examined the cumulative influence of candidate genes involved in the inflammatory response on long-term neurobehavioral recovery in children with early childhood TBI relative to children with orthopedic injuries (OI). Participants were drawn from a prospective, longitudinal study evaluating outcomes of children who sustained TBI (n = 67) or OI (n = 68) between age 3-7 years. Parents completed ratings of child executive function and behavior at an average of 6.8 years after injury. Exploratory unweighted and weighted polygenic risk scores (PRS) were constructed from single nucleotide polymorphisms (SNPs) across candidate inflammatory response genes (i.e., ACE, BDNF, IL1RN, and NT5E) that showed nominal (p ≤ .20) associations with outcomes in the TBI group. Linear regression models tested the PRS x injury group (TBI vs OI) interaction term and post hoc analyses examined the effect of PRS within each injury group. Higher inflammatory response PRS were associated with more executive dysfunction and behavior problems in children with TBI but not in children with OI. The cumulative influence of inflammatory response genes as measured by PRS explained additional variance in long-term neurobehavioral outcomes, over and above well-established predictors and single candidate SNPs tested individually. The results suggest that some of the unexplained heterogeneity in long-term neurobehavioral outcomes following pediatric TBI may be attributable to a child's genetic predisposition for a greater or lesser inflammatory response to TBI.

KEYWORDS:

BIOMARKERS; GENETIC FACTORS; INFLAMMATION; NEUROPSYCHOLOGY; PEDIATRIC BRAIN INJURY

PMID:
32024452
DOI:
10.1089/neu.2019.6866

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center