All ETDs from UAB

Advisory Committee Chair

Sadeep Shrestha

Advisory Committee Members

Marguerite R Irvin

Nita A Limdi

Edgar T Overton

Degui Zhi

Document Type

Dissertation

Date of Award

2016

Degree Name by School

Doctor of Philosophy (PhD) School of Public Health

Abstract

The purpose of this dissertation is to evaluate the association of local European ancestry (LEA) with subclinical and clinical cardiovascular (CV) disease (CVD) among African Americans in three prospective cohorts from the United States. CVD burden is higher among African Americans compared to other racial/ethnic groups and prevention efforts have led to the evaluation of subclinical measures of CVD such as carotid artery intima-media thickness (CIMT), and risk factors including the underlying genetic component of the disease. Admixed populations such as African Americans may have increased risk of disease as a result of the increased prevalence of a disease among their ancestral populations. This results in SNPs with increased allele frequencies in the ancestral populations with higher prevalence, and can be detected by evaluating the local ancestry at these SNPs by using admixture mapping methods. The first aim (chapter 3) evaluated the association of local European ancestry with common CIMT (cCIMT) among African Americans from the MESA cohort, and we found a genome-wide significant gene region on chromosome 11 in the SERGEF gene associated with higher cCIMT. This same region was also associated with higher odds of stroke but no other clinical CV events. The second aim (chapter 4) evaluated the genome-wide admixture as well as single SNP association with cCIMT among HIV-positive and HIV-negative African American women from the WIHS cohort. Association of cCIMT was observed with several single SNP and LEA gene regions, some of these overlapped and others were also common across both HIV-positive and HIV-negative individuals suggesting gene pathways most likely involved in the underlying atherosclerotic process, which may or may not be influenced by HIV-related risk factors. The third aim (chapter 5) evaluated clinical CV events and their association with LEA among African Americans from the ARIC cohort. Several LEA gene regions on chromosome 4 achieved genome-wide significance associated with myocardial infarction, and two with composite CVD events. We also replicated several LEA-cCIMT associations observed in the MESA cohort in aim 1, confirming our associations in the ARIC cohort. Overall, the LEA association with subclinical and clinical CVD among African Americans from the three prospective cohorts suggests that there is a significant admixture component involved in the pathogenesis of cardiovascular disease. We revealed several novel gene regions which need further replication and validation to confirm their ancestry associations with cardiovascular disease among African Americans.

Aim 1-chapter 2 supplemental files.xlsx (1400 kB)
Supplemental Data - Chapter 2

Aim 2-chapter 3 supplemental files.xlsx (18605 kB)
Supplemental Data - Chapter 3

Aim 3-chapter 4 supplemental files.xlsx (649 kB)
Supplemental Data - Chapter 4

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