Li, Yunqi
(2018)
Epigenome-wide association study of recovery outcomes of traumatic brain injury patients.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Background: Traumatic Brain Injury (TBI) is a leading cause of morbidity and morbidity among individuals under 45 years old, worldwide. It is unknown why patients with similar extent of injury, similar care, and similar demographic factors have different recovery outcomes. Previous studies using animal models have identified robust DNA methylation changes post-TBI. This project aims to detect CpGs whose methylation levels associate with TBI patients’ recovery outcomes in human subjects.
Methods: We obtained DNA methylation profiles of cerebrospinal fluid samples collected at three different time points, first or second day, third or fourth day, and fifth or sixth day post-TBI from 120 severe TBI patients. Measures of recovery were collected including Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS), Neurological Rating Scale (NRS), Anxiety (ANX), Depression (DEP), and Deiner Satisfaction with Life Scale (SWLS) at third month, sixth month, twelfth month, and twenty-fourth month post-TBI, as well as covariates such as age, gender, BMI, and smoking. We dichotomized the third-month GOS to create a binary variable, which is the first phenotype used in the regression model. We also clustered the patients into poor recovery group and good recovery group based on the last available GOS, DRS, NRS, ANX, DEP, SWLS records, which is the second recovery phenotype we analyzed. After quality control and methylation data normalization, we used a linear regression model with empirical Bayes moderation to assess the association between DNA methylation at 307,187 cytosine-phosphate-guanine (CpG) sites and two recovery phenotypes with adjustment for age, gender, and surrogate variables.
Result: No significant associations between CpG methylation and recovery outcomes were observed at the genome-wide threshold for statistical significance (2.4 x 10-7). 24 CpGs were suggestively associated with TBI recovery at p-value less than 1 x 10-5. Most of these were located in/near genes which are associated with neurological phenotypes.
Public Health Significance: This pilot project provides a framework for a proposal to collect a larger dataset with higher power to detect potential genes and pathways related to methylation change post-TBI, and has the potential to develop novel interventions or improve the efficacy of existing interventions.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
28 June 2018 |
| Date Type: |
Publication |
| Defense Date: |
16 April 2018 |
| Approval Date: |
28 June 2018 |
| Submission Date: |
27 April 2018 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
65 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Human Genetics |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Epigenome-wide Association Study, Traumatic Brain Injury |
| Date Deposited: |
28 Jun 2018 20:10 |
| Last Modified: |
01 May 2023 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/34460 |
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