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Positional Cloning of Adiposity Genes in Ethnic Minorities of the Insulin Resistance Atherosclerosis Family Study

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abstract
Obesity is defined as a clinically determined excess of body mass for a given body size. Complex obesity poses one of the greatest health threats to the developed world, mainly due to the comorbidities to which the obese are predisposed (ex. type 2 diabetes, cardiovascular disease, and cancer). The origin of obesity is the combination of an individual’s obesogenic environment, lifestyle, and predisposing genetic variation. The known physiologic profile of visceral adipose tissue suggests that it could be responsible for obesity’s pathogenicity. Furthermore, African Americans and Hispanic Americans are at a disproportionately higher risk for obesity compared to European Americans. Despite the severity of the “obesity epidemic,” little is known about the genetic components of polygenic obesity. Moreover, a majority of studies of the genetic contributors of obesity utilize only European-derived populations, often focusing solely on whole-body anthropometrics. This dissertation utilizes the Insulin Resistance Atherosclerosis Family Study (IRASFS), which is a multi-center cohort that consists of the extended families of Hispanic (recruited in San Antonio, TX and San Luis Valley, CO) and African Americans (recruited in Los Angeles, CA). A unique obesity genetics study, the IRASFS not only incorporates ethnic minority populations, but possesses direct adiposity phenotypes, such as cross-sectional, computed tomography (CT)-derived measurements of abdominal visceral and subcutaneous fat area The dissertation’s main objective is to determine the genetic components of obesity in the ethnic cohorts of the IRASFS through positional cloning of genes and genetic variants influencing intermediate adiposity phenotypes. Presented herein are descriptions of the methods used, and the results of, candidate adiposity gene analysis via comprehensive single nucleotide polymorphism (SNP) genetic association study. The research effort occurs during a time of transition from whole genome linkage mapping to genome-wide association study (GWAS) in human genetics, and this is reflected in its progression. Published results regarding the linkage-derived candidate gene Suppressor of Cytokine Signaling 3 (SOCS3), the GWAS-implicated Insulin Induced Gene 2 (INSIG2), and candidate genes suggested via GWAS in the IRASFS Hispanics are presented. Finally, initial results regarding candidates obtained through GWAS in the IRASFS African Americans are presented.
subject
Genetics
contributor
Talbert, Matthew (author)
Howard, Timothy (committee chair)
Donald, Bowden (committee member)
Barbara, Nicklas (committee member)
David, Herrington (committee member)
Hang, Shi (committee member)
date
2009-12-16T15:50:45Z (accessioned)
2010-06-18T18:58:22Z (accessioned)
2009-12-16T15:50:45Z (available)
2010-06-18T18:58:22Z (available)
2009-12-16T15:50:45Z (issued)
degree
Molecular Medicine (discipline)
identifier
http://hdl.handle.net/10339/14758 (uri)
language
en_US (iso)
publisher
Wake Forest University
rights
Release the entire work for access only to the Wake Forest University system for one year from the date below. After one year, release the entire work for access worldwide. (accessRights)
title
Positional Cloning of Adiposity Genes in Ethnic Minorities of the Insulin Resistance Atherosclerosis Family Study
type
Dissertation

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