Genome-wide mapping of human loci for essential hypertension

Caulfield, Mark, Munroe, Patricia, Pembroke, Janine, Samani, Nilesh, Dominiczak, Anna, Brown, Morris, Benjamin, Nigel, Webster, John, Ratcliffe, Peter, O'Shea, Suzanne, Papp, Janet, Taylor, Elizabeth, Dobson, Richard, Knight, Joanne, Newhouse, Stephen, Hooper, Joel, Lee, Wai, Brain, Nick, Clayton, David, Lathrop, G. Mark, Farrall, Martin, Connell, John and MRC British Genetics of Hypertension Study (2003) Genome-wide mapping of human loci for essential hypertension. Lancet, 361 9375: 2118-2123. doi:10.1016/S0140-6736(03)13722-1


Author Caulfield, Mark
Munroe, Patricia
Pembroke, Janine
Samani, Nilesh
Dominiczak, Anna
Brown, Morris
Benjamin, Nigel
Webster, John
Ratcliffe, Peter
O'Shea, Suzanne
Papp, Janet
Taylor, Elizabeth
Dobson, Richard
Knight, Joanne
Newhouse, Stephen
Hooper, Joel
Lee, Wai
Brain, Nick
Clayton, David
Lathrop, G. Mark
Farrall, Martin
Connell, John
MRC British Genetics of Hypertension Study
Title Genome-wide mapping of human loci for essential hypertension
Journal name Lancet   Check publisher's open access policy
ISSN 0140-6736
1474-547X
Publication date 2003-06-21
Sub-type Article (original research)
DOI 10.1016/S0140-6736(03)13722-1
Volume 361
Issue 9375
Start page 2118
End page 2123
Total pages 6
Place of publication London, England
Publisher Lancet Publishing Group
Language eng
Subject 0604 Genetics
1102 Cardiovascular Medicine and Haematology
Formatted abstract
Background:
Blood pressure may contribute to 50% of the global cardiovascular disease epidemic. By understanding the genes predisposing to common disorders such as human essential hypertension we may gain insights into novel pathophysiological mechanisms and potential therapeutic targets. In the Medical Research Council BRItish Genetics of HyperTension (BRIGHT) study, we aim to identify these genetic factors by scanning the human genome for susceptibility genes for essential hypertension. We describe the results of a genome scan for hypertension in a large white European population.

Methods:

We phenotyped 2010 affected sibling pairs drawn from 1599 severely hypertensive families, and completed a 10 centimorgan genome-wide scan. After rigorous quality control, we analysed the genotypic data by non-parametric linkage, which tests whether genes are shared in excess among the affected sibling pairs. Lod scores, calculated at regular points along each chromosome, were used to assess the support for linkage.

Findings:
Linkage analysis identified a principle locus on chromosome 6q, with a lod score of 3.21 that attained genome-wide significance (p=0.042). The inclusion of three further loci with lod scores higher than 1.57 (2q, 5q, and 9q) also show genome-wide significance (p=0.017) when assessed under a locus-counting analysis.

Interpretation:

These findings imply that human essential hypertension has an oligogenic element (a few genes may be involved in determination of the trait) possibly superimposed on more minor genetic effects, and that several genes may be tractable to a positional cloning strategy.
Keyword Sib-Pair Linkage
Material Susceptibility Locus
Blood-pressure
Complex Traits
Scans
Preeclampsia
Chromosome-2
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Tue, 07 Sep 2010, 10:01:57 EST