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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Multilocus analysis of hypertension: A hierarchical approach
Human Heredity, Volume 57, No. 1, Year 2004
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Description
While hypertension is a complex disease with a well-documented genetic component, genetic studies often fail to replicate findings. One possibility for such inconsistency is that the underlying genetics of hypertension is not based on single genes of major effect, but on interactions among genes. To test this hypothesis, we studied both single locus and multilocus effects, using a case-control design of subjects from Ghana. Thirteen polymorphisms in eight candidate genes were studied. Each candidate gene has been shown to play a physiological role in blood pressure regulation and affects one of four pathways that modulate blood pressure: vasoconstriction (angiotensinogen, angiotensin converting enzyme - ACE, angiotensin II receptor), nitric oxide (NO) dependent and NO independent vasodilation pathways and sodium balance (G protein-coupled receptor kinase, GRK4). We evaluated single site allelic and genotypic associations, multilocus genotype equilibrium and multilocus genotype associations, using multifactor dimensionality reduction (MDR). For MDR, we performed systematic reanalysis of the data to address the role of various physiological pathways. We found no significant single site associations, but the hypertensive class deviated significantly from genotype equilibrium in more than 25% of all multilocus comparisons (2,162 of 8,178), whereas the normotensive class rarely did (11 of 8,178). The MDR analysis identified a two-locus model including ACE and GRK4 that successfully predicted blood pressure phenotype 70.5% of the time. Thus, our data indicate epistatic interactions play a major role in hypertension susceptibility. Our data also support a model where multiple pathways need to be affected in order to predispose to hypertension. Copyright © 2004 S. Karger AG, Basel.
Authors & Co-Authors
Williams, Scott M.
United States, Nashville
Vanderbilt University Medical Center
United States, Nashville
Meharry Medical College
Ritchie, Marylyn D.
United States, Nashville
Vanderbilt University Medical Center
Phillips, John Atlas
United States, Nashville
Vanderbilt University Medical Center
United States, Nashville
Meharry Medical College
Dawson, Elliott P.
United States, Murfreesboro
Bioventures, Inc.
Prince, Melissa A.
United States, Nashville
Vanderbilt University Medical Center
Dzhura, Elvira V.
United States, Nashville
Vanderbilt University Medical Center
Willis, Alecia S.
United States, Nashville
Vanderbilt University Medical Center
Semenya, Amma
United States, Nashville
Meharry Medical College
Summar, Marshall
United States, Nashville
Vanderbilt University Medical Center
White, Bill C.
United States, Nashville
Vanderbilt University Medical Center
Addy, Jonathan H.
Ghana, Accra
University of Ghana
Kpodonu, John
Ghana, Accra
University of Ghana
Wong, Leejun C.
United States, Washington, D.c.
Georgetown University Medical Center
Felder, Robin A.
United States, Charlottesville
University of Virginia School of Medicine
José, Pedro A.
United States, Washington, D.c.
Georgetown University Medical Center
Moore, Jason H.
United States, Nashville
Vanderbilt University Medical Center
Statistics
Citations: 158
Authors: 16
Affiliations: 6
Identifiers
Doi:
10.1159/000077387
ISSN:
00015652
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Case-Control Study
Study Locations
Ghana