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Epigenome-wide association study of recovery outcomes of traumatic brain injury patients

Li, Yunqi (2018) Epigenome-wide association study of recovery outcomes of traumatic brain injury patients. Master's Thesis, University of Pittsburgh. (Unpublished)

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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:
CreatorsEmailPitt UsernameORCID
Li, YunqiYUL164@pitt.eduYUL164
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairShaffer, Johnjohn.r.shaffer@pitt.edu
Committee CoChairWeeks, Danielweeks@pitt.edu
Committee MemberConley, Yvetteyconley@pitt.edu
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: Graduate 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: 28 Jun 2018 20:10
URI: http://d-scholarship.pitt.edu/id/eprint/34460

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