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Epigenome-wide Association studies in aneurysmal subarachnoid hemorrhage patients

Arockiaraj, Annie Infancia (2019) Epigenome-wide Association studies in aneurysmal subarachnoid hemorrhage patients. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a form of stroke with a prominent health burden. aSAH has varied outcomes in people ranging from cognitive impairment, functional disability, emotional dysfunction, coma, and death. The reason for the varied outcomes after aSAH is unknown. Previous studies showed altered DNA methylation to be associated with higher mortality after stroke. Altered DNA methylation might play a role in the varied outcomes experienced by individuals after aSAH. In this study, we analyze the association between DNA methylation and clinical outcomes in aSAH individuals.
Method: We analyzed five serial samples of cerebrospinal fluid (CSF) from days 1, 4, 7, 10 and 13 post injury from 279 subjects and blood samples from a subset of 88 of these individuals on day 1. Phenotypes including age, sex, race, smoking status, height and weight were recorded. Clinical outcomes such as delayed cerebral ischemia (DCI) status and vasospasm were recorded. Recovery outcomes such as Glasgow Outcome Scale (GOS) and Modified Ranking Scale (MRS) were measured at both 3 months and 12 months post aSAH. The methylation levels for the samples were assessed using Illumina Infinium 450k methylation chips. The outcomes were dichotomized and a linear regression model with empirical Bayes moderation was constructed to assess the association between methylation at ~ 400,000 cytosine-phosphate-guanine sites (CpGs) and clinical outcomes. The model was adjusted for age, gender, and surrogate variables. A total of 26 epigenome-wide association analyses (EWASes) were performed.
Result: We found significant association between cg18031596 and DCI in the blood samples (1.3  10-7) that passed the genome-wide significance threshold (2.4  10-7). The CpG is near the angiopoietin gene (ANGPT1). Previous studies showed the role of angiopoietin 1 protein in aneurysms. Many CpGs showed suggestive significance (p < 1  10-5) in the 26 EWASes.
Public Health Significance: This study suggests the association of methylation with DCI in aSAH individuals. This discovery supports future replication studies to explore the relationship between methylation and DCI in aSAH individuals. Understanding the changes in DNA methylation that occur in aSAH patients may ultimately lead to interventions to improve the quality of life.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Arockiaraj, Annie Infanciainfancia.annie@gmail.comana100@pitt.edu
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairShaffer, Johnjohn.r.shaffer@pitt.edu
Committee CoChairWeeks, Danielweeks@pitt.edu
Committee MemberConley, Yvette Perryyconley@pitt.edu
Date: 19 July 2019
Date Type: Publication
Defense Date: 24 May 2019
Approval Date: 19 July 2019
Submission Date: 19 June 2019
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 88
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: Aneurysmal subarachnoid hemorrhage (aSAH), epigenome-wide association analyses, DNA methylation
Date Deposited: 19 Jul 2019 19:28
Last Modified: 19 Jul 2019 19:28
URI: http://d-scholarship.pitt.edu/id/eprint/36972

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