Heritability and a genome-wide linkage scan for arterial stiffness, wave reflection, and mean arterial pressure: The Framingham heart study

Gary F. Mitchell, Anita L. DeStefano, Martin G. Larson, Emelia J. Benjamin, Ming Huei Chen, Ramachandran S. Vasan, Joseph A. Vita, Daniel Levy

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

Background-Arterial stiffness and mean arterial pressure variably contribute to systolic hypertension and increased cardiovascular risk. However, few prior community-based studies have evaluated the genetics of arterial stiffness and separate mean and pulsatile components of blood pressure. Methods and Results-Using arterial tonometry, we evaluated heritability and linkage of forward and reflected wave amplitude, mean arterial pressure, and carotid-femoral pulse wave velocity (CFPWV) in 1480 participants representing 817 pedigrees in the Framingham Study offspring cohort. In 204 families with tonometry data, a genome-wide scan was performed with microsatellite markers that covered the genome at 10-cM intervals. Heritability estimates were moderate for reflected wave amplitude (h2=0.48), forward wave amplitude (h2=0.21), CFPWV (h2=0.40), and mean arterial pressure (h2=0.33). Variance components linkage analysis identified 2 regions of linkage for reflected wave amplitude: chromosome 4 at 181 cM (logarithm of odds [LOD]=4.93, permuted P=0.002) and chromosome 8 at 33 cM (LOD=3.27, permuted P=0.058). There was 1 region of linkage for forward wave amplitude on chromosome 7 at 174 cM (LOD=2.88, permuted P=0.017). There were several regions of suggestive linkage for CFPWV: chromosome 2 at 94 cM (LOD=2.46), chromosome 7 at 29 cM (LOD=2.50), chromosome 13 at 108 cm (LOD=2.10), and chromosome 15 at 108 cM (LOD=2.48). There was 1 region of suggestive linkage for mean arterial pressure on chromosome 1 at 192 cM (LOD=2.18). Conclusions-Arterial stiffness measures and mean and pulsatile components of blood pressure are heritable and appear to have genetic determinants that may be linked to separate genetic loci in humans.

Original languageEnglish (US)
Pages (from-to)194-199
Number of pages6
JournalCirculation
Volume112
Issue number2
DOIs
StatePublished - Jul 12 2005
Externally publishedYes

Keywords

  • Arteries
  • Arteriosclerosis
  • Blood pressure
  • Elasticity
  • Genetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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