Obesity Clinical Trial
Official title:
Genomic Dissection of a QTL Affecting the Lipid Profile
To search for the genetic cause of the metabolic syndrome, a lipid disorder that poses a major risk for coronary heart disease.
BACKGROUND:
The metabolic syndrome is a common disorder posing a significant major risk for coronary
heart disease and early mortality in the Western hemisphere. Central to its cardiovascular
complications is the association of the syndrome with the specific abnormalities in plasma
lipid and lipoprotein profiles including increased plasma triglycerides, decreased HDL
cholesterol, and predominance of dense lipoprotein particles. In search for the genetic
etiology of this lipid disorder, the investigators identified a quantitative trait locus
(QTL) on human chromosome 7q36 strongly linked to variation in plasma lipid levels. They
hypothesize that this QTL contains genetic variants that contribute to alterations in
biologic pathways underlying the genesis of the lipid disorder.
DESIGN NARRATIVE:
The study will search for the genetic cause of the metabolic syndrome, a lipid disorder that
poses a major risk for coronary heart disease. The investigators have identified a
quantitative trait locus (QTL) on human chromosome 7q36 strongly linked to variation in
plasma lipid levels. The investigators hypothesize that this QTL contains genetic variants
that contribute to alterations in biologic pathways underlying the genesis of the lipid
disorder. To test for this hypothesis, they propose a comprehensive approach utilizing
established resources and expertise to identify the functional sequence variants within this
QTL. Specifically, they will 1.) identify single nucleotide polymorphisms (SNPs) and their
haplotype and linkage disequilibrium structure across the entire QTL region; 2.) Analyze
association of informative SNPs with plasma triglyceride levels, LDL levels, and lipoprotein
density fractions using variance component linkage/disequilibrium analyses; and 3.) Identify
potentially functional sequence variants in associated genes or genomic regions using
Bayesian quantitative trait nucleotide analysis. This comprehensive application of newly
available genomic technologies, novel statistical approaches, the DNA and phenotypic
information available, and the consortium of expertise assembled behind this project will
ensure the successful elucidation of the genetic etiology of this lipid disorder and
consequently the development of effective means for prevention and/or treatment of
cardiovascular complications of the metabolic syndrome.
;
Observational Model: Cohort, Time Perspective: Cross-Sectional
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