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University of North Carolina

1. Marvelle, Amanda F. The genetics of obesity-related traits and lipoproteins in Filipino women.

Degree: 2010, University of North Carolina

The underlying genetic component of risk factors for cardiovascular disease (CVD) is not well understood. Recently, advances in high-throughput genotyping, single nucleotide polymorphism (SNP) discovery, and the development of databases such as the International Haplotype Map (HapMap) have provided scientists with tools to complete a genetic analysis of complex diseases such as CVD. Research presented in this dissertation aims to further understand the genetics of obesity-related traits and lipoprotein levels and identify variants that are associated with these traits in a cohort of adult women from metro Cebu, Philippines, who participated in the Cebu Longitudinal Health and Nutrition Survey (CLHNS). Initially I assess the transferability of tag SNPs chosen from HapMap panels to the CLHNS. I show that the Asian HapMap samples are an effective resource for studies in the CLHNS. I then investigate the association between 19 candidate variants in 10 genes previously reported to be associated with obesity-related traits with similar traits in the CLHNS. We observe evidence for association with the A-allele of rs9939609 of FTO and ADRB3 Trp64-allele with obesity traits. I perform a genome-wide association study for HDL-C, triglycerides, LDL-C, and total cholesterol. Among ~2 million SNPs analyzed, we observe evidence of association for 11 loci previously described. We observe suggestive evidence of trait association (P <10-5) for Tankyrase (TNKS) with LDL-C and Collecting-12 (COLEC12) with total cholesterol. In a separate study, I investigate an HDL-C associated locus, GALNT2, to identify functional variants responsible for the association signal. I identify variants in moderate linkage disequilibrium (r2 >.5) with HDL-C associated SNPs, clone regions that have suggestive regulatory function into a luciferase reporter vector, and measure transcriptional activity in HepG2 cells. The results suggest that a 21 bp deletion, rs4849913, and/or rs2144300 may act to increase the transcriptional activity of GALNT2 or an unknown novel intronic transcript to increase HDL-C. These studies present the first genetic study of CVD traits in the CLHNS and a molecular study of a gene that is associated with HDL-C. Together this research provides a solid foundation for one day identifying the molecular mechanism underlying complex diseases. Advisors/Committee Members: Marvelle, Amanda F., Mohlke, Karen.

Subjects/Keywords: School of Medicine; Curriculum in Genetics and Molecular Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Marvelle, A. F. (2010). The genetics of obesity-related traits and lipoproteins in Filipino women. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:f8d8fb5f-32fd-4bbb-a8f7-cdda342bc1a6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Marvelle, Amanda F. “The genetics of obesity-related traits and lipoproteins in Filipino women.” 2010. Thesis, University of North Carolina. Accessed August 05, 2020. https://cdr.lib.unc.edu/record/uuid:f8d8fb5f-32fd-4bbb-a8f7-cdda342bc1a6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Marvelle, Amanda F. “The genetics of obesity-related traits and lipoproteins in Filipino women.” 2010. Web. 05 Aug 2020.

Vancouver:

Marvelle AF. The genetics of obesity-related traits and lipoproteins in Filipino women. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2020 Aug 05]. Available from: https://cdr.lib.unc.edu/record/uuid:f8d8fb5f-32fd-4bbb-a8f7-cdda342bc1a6.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Marvelle AF. The genetics of obesity-related traits and lipoproteins in Filipino women. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:f8d8fb5f-32fd-4bbb-a8f7-cdda342bc1a6

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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