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Replication Study of Plasma Lipoprotein Levels-Associated Polymorphisms Identified in Recent Genome-Wide Association Studies

Bryant, Emily Kate (2011) Replication Study of Plasma Lipoprotein Levels-Associated Polymorphisms Identified in Recent Genome-Wide Association Studies. Master's Thesis, University of Pittsburgh. (Unpublished)

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Cardiovascular disease (CVD) is a major public health concern in the U.S., and is the leading cause of death for both men and women. Abnormal plasma lipoprotein levels, especially low high-density lipoprotein cholesterol (HDL-C) levels, are among major factors that influence the CVD risk. Functional and candidate gene association studies and recent genome-wide association studies (GWAS) have identified several genes as being potentially significant for HDL-C and other lipid (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TG]) levels. Our group has been comprehensively investigating several HDL-C levels-associated genes using sequencing and genotyping methods to test both common and rare variant hypotheses. In this study, we sought to replicate the GWAS signals from other genes that have not been targeted by our sequencing effort in three epidemiological samples, U.S. non-Hispanic Whites, U.S. Hispanics, and African Blacks. We selected 40 SNPs (primarily those influencing the HDL-C levels) for analysis and genotyped each SNP in all populations when present at sufficient frequency (6 SNPs were not analyzed in Blacks). For 25 SNPs, we were able to replicate the genome-wide significant associations with the same lipid trait in the same direction in at least one ethnic group studied: at nominal significance (p<0.05) for 14 SNPs, with marginal p-values (0.05-0.10) for 3 SNPs, and with trend for association with p-values between 0.10-0.20 for 8 SNPs. Similarly, we were able to replicate 18 of 37 SNPs for HDL-C, 5 of 6 SNPs for TC, 5 of 7 SNPs for TG, and 2 SNPs for LDL-C levels. Two SNPs showed significant (p<0.05) but discordant results for association with the HDL-C levels as compared to those reported in the original GWAS. For 10 SNPs, we observed significant associations with lipid traits other than those reported as genome-wide significant in the original GWAS. Identification and replication of genetic associations with plasma lipid levels is relevant to public health as it may lead to improvements in prevention and treatment of dyslipidemia, which is a major risk factor for heart disease.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Bryant, Emily
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDemirci, F Yesimfyd1@pitt.eduFYD1
Committee MemberBunker, Clareann HBUNKERC@pitt.eduBUNKERC
Committee MemberKamboh, M Ilyaskamboh@pitt.eduKAMBOH
Date: 29 June 2011
Date Type: Completion
Defense Date: 13 April 2011
Approval Date: 29 June 2011
Submission Date: 5 April 2011
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
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: cardiovascular disease; HDL-C; lipid; SNP
Other ID:, etd-04052011-174431
Date Deposited: 10 Nov 2011 19:34
Last Modified: 15 Nov 2016 13:38


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