New susceptibility locus for hypertension on chromosome 8q by efficient pedigree-breaking in an Italian isolate

Hum Mol Genet. 2006 May 15;15(10):1735-43. doi: 10.1093/hmg/ddl097. Epub 2006 Apr 12.

Abstract

Essential hypertension (EH) affects a large proportion of the adult population in Western countries and is a major risk factor for cardiovascular diseases. EH is a multifactorial disease with a complex genetic component. To tackle the complexity of this genetic component, we have initiated a study of Campora, an isolated village in South Italy. A random sample of 389 adults was genotyped for a very dense microsatellite genome scan and phenotyped for EH. Of this sample, 173 affected individuals were all related through a 2,180-member pedigree and could be integrated within a linkage analysis. The complexity of the pedigree prevented its direct use for a non-parametric linkage (NPL) analysis. Therefore, the method proposed by Falchi et al. [2004, Am. J. Hum. Genet., 75, 1015-1031] was used for automatic pedigree-breaking. We identified a new locus for EH on chromosome 8q22-23 and detected linkage with two known loci for EH: 1q42-43 and 4p16. Simulations showed that the linkage with 8q22-23 is highly genome-wide significant, even when accounting for the breaking of the pedigree. An extension to qualitative traits of another pedigree-breaking approach [Pankratz et al., 2001, Genet. Epidemiol., 21 (Suppl. 1), S258-S263] also detected a significant linkage on 8q22-23 using a remarkably different set of sub-pedigrees and helped to refine the location of the linkage signal. This work both identifies a new locus strongly linked to hypertension and shows that the power of linkage analysis can be improved by the appropriate use of efficient pedigree-breaking strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 8 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome, Human / genetics
  • Genotype
  • Humans
  • Hypertension / epidemiology
  • Hypertension / genetics*
  • Italy
  • Linkage Disequilibrium*
  • Male
  • Microsatellite Repeats / genetics*
  • Pedigree
  • Phenotype
  • Quantitative Trait Loci*