title: AGT genetic variation, plasma AGT, and blood pressure: An analysis of the Utah Genetic Reference Project pedigrees.
abstract: BACKGROUND
  Much remains unknown about the genetic factors that contribute to essential hypertension. The Utah Genetic Reference Project (UGRP) large pedigree collection provides new opportunities to study quantitative relationships between genetic variation, endophenotypes, and blood pressure.
  
  
  METHODS
  We analyzed the relationship between common single-nucleotide polymorphisms (SNPs) and haplotypes spanning the angiotensinogen (AGT) gene and promoter region, plasma AGT levels, and systolic (SBP) and diastolic blood pressure (DBP) in 424 individuals from 41 two-generation UGRP families.
  
  
  RESULTS
  Plasma AGT levels are significantly correlated among UGRP family members. Correlations are higher for males than for females. Parent-offspring correlations for plasma AGT (0.30) are higher than those for SBP (0.26) and DBP (0.17) (all P values <0.01). The additive heritability (h(2)) for plasma AGT is high (0.74) and substantially exceeds heritability estimates for SBP (0.26) and DBP (0.16) (all P values <0.01). Significant linkage (logarithm of the odds (LOD) >3) is found between six AGT SNPs and plasma AGT. A model that utilizes three AGT haplotype groups produces the best LOD score (5.1) that exceeds the best single SNP LOD score (3.8). Plasma AGT and blood pressure were not significantly correlated.
  
  
  CONCLUSIONS
  Plasma AGT levels demonstrate high heritability in 41 UGRP families. Locus-specific heritability estimates for AGT SNPs and haplotypes approach 67%, indicating that variation at AGT accounts for a large percentage of the heritability of plasma AGT. A three-way haplotype model outperforms single SNPs for quantitative linkage analysis to plasma AGT. In these predominantly normotensive individuals, plasma AGT did not correlate significantly with blood pressure.
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, USA.
authors.forename: W Scott
authors.initials: WS
authors.lastname: Watkins
authors.forename: Andreas
authors.initials: A
authors.lastname: Rohrwasser
authors.forename: Andy
authors.initials: A
authors.lastname: Peiffer
authors.forename: Mark F
authors.initials: MF
authors.lastname: Leppert
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lalouel
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
mesh_terms: D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
chemical_list: D000808:Angiotensinogen