# Genetic and Environmental Influences on Recovery of Severe Pediatric Brain Injury.

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $559,661

## Abstract

Summary
 There is substantial variation in recovery after pediatric traumatic brain injury (TBI). If we could
understand the underpinnings behind this variation, then treatments could be optimized to reduce the profound
negative societal and economic impact associated with pediatric TBI. Predictors of recovery following TBI,
particularly the roles of genes and environment, are incompletely understood. Elucidation of genetic and
environmental influences on recovery after pediatric TBI is critically needed to advance development of
precision medicine strategies. Novel systems biology analyses conducted by our group indicate genetic factors
within two main biologic processes, response to injury (cell proliferation, cell death, inflammatory response,
cellular metabolism) and neurocognitive and behavioral reserve (neurodevelopment, cognition, and behavior),
are likely associated with recovery after TBI. An approach that seeks to identify genes and variants over-
represented (gene-enrichment) across these biologic processes would improve upon prior candidate gene
approaches. Genetic variants implicated in recovery after TBI interact with home and family environmental
factors to influence cognitive and behavioral outcomes in other pediatric populations; however, the effects of
the interaction between genes and environment on recovery after pediatric TBI have not been explored. The
objective of this proposal is to understand the interplay between genetically influenced biologic processes and
environment with respect to recovery after pediatric TBI. We hypothesize that genetic variants overrepresented
in biologic processes important to TBI recovery will be associated with global, neurocognitive, and
neurobehavioral functioning and that environmental factors will interact with genetic factors to influence
recovery after severe pediatric TBI. We will collect salivary DNA samples from approximately 338 children
participating in the Approaches and Decisions in Acute Pediatric TBI Trial (ADAPT, U01 NS081041). The
primary outcome will be global functioning assessed by the pediatric Glasgow Outcome Scale-Extended
(GOSE) at 3, 6, and 12 months post injury and secondary outcomes will include a comprehensive assessment
of cognitive and behavioral functioning at 12 months post injury. We will use an analytic approach that seeks to
identify genes and variants associated with recovery that are over-represented (gene-enrichment) across
response to injury and neurocognitive and behavioral reserve biologic processes. Mixed model analyses will be
used to evaluate the association of genotypes with recovery after severe pediatric TBI and to elucidate the
association of environmental factors (family functioning, parenting practices, home environment, and
socioeconomic status) with recovery. How genetic and environmental factors and genetic and early clinical
factors interact to influence recovery after severe pediatric TBI will also be evaluated. This project will provide
cr...

## Key facts

- **NIH application ID:** 9933091
- **Project number:** 5R01NS096053-05
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Brad G Kurowski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $559,661
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933091

## Citation

> US National Institutes of Health, RePORTER application 9933091, Genetic and Environmental Influences on Recovery of Severe Pediatric Brain Injury. (5R01NS096053-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933091. Licensed CC0.

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