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Genetic Variability of EDIL3 in Aneurysmal Subarachnoid Hemorrhage

Deslouches, Sandra (2024) Genetic Variability of EDIL3 in Aneurysmal Subarachnoid Hemorrhage. Master's Thesis, University of Pittsburgh. (Unpublished)

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Aneurysmal subarachnoid hemorrhage (aSAH) results from a ruptured brain aneurysm leading to severe stroke with varying outcomes, ranging from cognitive decline to long-term disability, and death. The study used existing genome-wide association and DNA methylome data from an aSAH cohort to address the hypothesis that Epidermal Growth Factor-like repeats and Discoidin I-like Domains 3 (EDIL3) single nucleotide polymorphisms (SNPs) and DNA methylation will be associated with delayed cerebral ischemia (DCI), Glasgow Outcome Scale (GOS) and Modified Rankin Scale (mRS).
Aim 1 evaluated the relationship between EDIL3 SNPs and patient outcomes (n=197) using logistic regression analysis. Significant associations were observed between DCI and three SNPs: rs16901000 (OR: 0.385, CI: 0.147 – 0.891, p= 0.036), rs16901053 (OR: 0.343, CI: 0.137 – 0.774, p= 0.014), and rs16901061 (OR: 0.325. CI: 0.136 – 0.709, p= 0.007). Similarly, GOS was associated with SNPs, rs4612038 at 3 months (OR: 1.819, CI: 1.009 – 3.366, p= 0.049), rs2301103 at both 3 (OR: 2.857, CI: 1.233 – 6.908, p= 0.016) and 12 months (OR: 2.539, CI: 1.053 – 6.306, p= 0.039), and rs13165263 at 12 months (OR: 2.382, CI: 1.086 – 5.277, p= 0.03). No associations were observed with mRS at 3 or 12 months, including the methylation sites.
Aim 2 involved collapsing the DNA methylation data from cerebrospinal fluid samples collected longitudinally (n=260) at five cross-sectional time points using logistic regression analysis. Three CpG sites showed significant association with DCI, and eleven sites with GOS at 3 and/or 12 months. These CpG sites mainly showed protective effects for both short- and long-term outcomes, except for cg07690181, which conferred an increased risk of developing DCI.
Finally, Aim 3 evaluated whether the outcome-associated lead SNP (from Aim 1) was a potential Methylation Quantitative Trait Locus (meQTL) by performing linear regression analysis in 117 subjects for whom both the SNP and methylation data were available. The most significant (lead) SNP from Aim 1, rs16901061, was found to function as an meQTL.
The results suggest that EDIL3 could be a potential target for public health intervention, focusing on the polymorphisms and the DNA methylation sites to manage short- and long-term outcomes.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Deslouches, Sandrasdeslouc@pitt.edusdeslouc
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairConley, Yvetteyconley@pitt.eduyconley
Committee MemberDemirci, F. Yesimfyd1@pitt.edufyd1
Committee MemberShaffer, John R.john.r.shaffer@pitt.edujohn.r.shaffer
Date: 2 January 2024
Date Type: Publication
Defense Date: 6 December 2023
Approval Date: 2 January 2024
Submission Date: 14 December 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 47
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: Aneurysmal subarachnoid hemorrhage (aSAH) EDIL3 Delayed cerebral ischemia (DCI) Glasgow Outcome Scale (GOS) Modified Rankin Scale (mRS) DNA methylation Polymorphism
Date Deposited: 02 Jan 2024 16:48
Last Modified: 02 Jan 2024 16:48


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