title: Genome-wide mapping of human loci for essential hypertension.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine, London, UK. m.j.caulfield@qmul.ac.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Caulfield
authors.forename: Patricia
authors.initials: P
authors.lastname: Munroe
authors.forename: Janine
authors.initials: J
authors.lastname: Pembroke
authors.forename: Nilesh
authors.initials: N
authors.lastname: Samani
authors.forename: Anna
authors.initials: A
authors.lastname: Dominiczak
authors.forename: Morris
authors.initials: M
authors.lastname: Brown
authors.forename: Nigel
authors.initials: N
authors.lastname: Benjamin
authors.forename: John
authors.initials: J
authors.lastname: Webster
authors.forename: Peter
authors.initials: P
authors.lastname: Ratcliffe
authors.forename: Suzanne
authors.initials: S
authors.lastname: O'Shea
authors.forename: Jeanette
authors.initials: J
authors.lastname: Papp
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Taylor
authors.forename: Richard
authors.initials: R
authors.lastname: Dobson
authors.forename: Joanne
authors.initials: J
authors.lastname: Knight
authors.forename: Stephen
authors.initials: S
authors.lastname: Newhouse
authors.forename: Joel
authors.initials: J
authors.lastname: Hooper
authors.forename: Wai
authors.initials: W
authors.lastname: Lee
authors.forename: Nick
authors.initials: N
authors.lastname: Brain
authors.forename: David
authors.initials: D
authors.lastname: Clayton
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: John
authors.initials: J
authors.lastname: Connell
mesh_terms: D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D035781:Siblings