A genome wide scan for early onset primary hypertension in Scandinavians

Hum Mol Genet. 2003 Aug 15;12(16):2077-81. doi: 10.1093/hmg/ddg206.

Abstract

With the aim of identifying hypertension susceptibility loci, we performed a genome wide scan in Scandinavian sib-pairs with early onset primary hypertension. To be classified as affected, a diagnosis of primary hypertension at age </=50 years was required. Two hundred and forty three patients with onset of primary hypertension at 40.0+/-7.7 (mean+/-SD) years from 91 families (91 sib-ships with a mean of 2.7 and a range of 2-6 affected members per sib-ship) were genotyped with 362 microsatellite markers with a density of approximately 10 cM. Loci obtaining nominal P</=0.016 (LOD score >/= 1.0) were fine mapped with additional markers. Multipoint non-parametric linkage analysis was performed using GENEHUNTER v 2.0. Using simulations, a nominal P</=0.0002 was determined to be a genome wide significant evidence of linkage. In the 10 cM genome wide scan, nominal P</=0.016 were found on chromosomes 1 at 81 cM (P=0.007), 2 at 115 cM (P=0.006), 3 at 108 cM (P=0.006), 14 at 45 cM (P=0.0002) and at 99 cM (P=0.001), 17 at 42 cM (P=0.015) and 19 at 89 cM (P=0.007). After fine mapping of these loci, one of the chromosome 14 loci just obtained the level of genome wide significance (P=0.0002 at 41 cM) and the chromosome 2 locus reached suggestive evidence of linkage (P=0.002 at 118 cM). Our data suggest a hypertension susceptibility locus on chromosome 14 around 41 cM. The locus on chromosome 2 is also promising as it has been implicated in hypertension and blood pressure regulation in earlier genome scans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 2
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genetic Testing*
  • Humans
  • Hypertension / diagnosis
  • Hypertension / genetics*
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Norway
  • Siblings
  • Sweden

Substances

  • Genetic Markers