The Contribution of Genetic Risk for Alzheimer’s & Cardiovascular Disease to Recovery from Traumatic Brain Injuries
Polygenic risk scores (PRS) represent the genetic likelihood of developing a phenotype and represent an exciting opportunity for the development of personalized medicine. This study used PRS to determine if individuals at high-risk for Alzheimer’s (AD) or cardiovascular disease (CVD) would recover differently after TBI compared to low-risk individuals.
GWAS with the Illumina Global Screening Array was performed on DNA available for a subset of the BI-Model Systems cohort (N=189). PRS were chosen from the PGS Catalog (https://www.pgscatalog.org) and calculated using the Michigan Imputation Server. 1-year follow-up data (1Y) for the Functional Independence Measure (FIM) was used to evaluate TBI recovery. FIM represents the subject’s self-care ability after TBI and includes a cognitive and motor component.
ANCOVA models were used to elucidate the relationship between PRS risk groups (score in top 20% vs. 80%) and 1Y FIM scores. Covariates included age, education, FIM scores at discharge, injury severity, and genetic ancestry. Post-hoc analysis was conducted using 1Y FIM scores of subjects stratified by AD risk and APOE e4 carrier status, a major risk factor for AD onset. Additional post-hoc analysis evaluated hypertension at 1Y by CVD PRS groups using a cox survival model.
Individuals with high AD PRS had lower 1Y FIM scores than those with low risk (p= 0.041). Post-hoc analysis showed a trend for APOE e4 carriers with high AD PRS performing worse on FIM motor testing (p=0.145). There was not significant association between the CVD high-risk group and FIM scores (p=0.389). The cox survival model of hypertension trended towards earlier age of onset in the high-risk subjects (p=0.155).
This pilot study shows the potential for PRS to identify individuals at risk for worse TBI recovery, allowing for future research on early interventions and their effects on TBI recovery.
Copyright (c) 2022 Ethan Wood, Kelly K. Nudelman, PhD
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