Autosomal genome-wide scan for coronary artery calcification loci in sibships at high risk for hypertension

Leslie A. Lange, Ethan M. Lange, Lawrence F. Bielak, Carl D. Langefeld, Sharon L. Kardia, Patrick Royston, Stephen T. Turner, Patrick F. Sheedy, Eric Boerwinkle, Patricia A. Peyser

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Coronary artery disease (CAD) is the leading cause of mortality in the developed world. Although several CAD risk factors, including measures of lipid metabolism, obesity, and blood pressure, have a genetic basis, many genes for CAD susceptibility have yet to be identified. Coronary atherosclerosis is the major cause of CAD, but many with coronary atherosclerosis lack symptoms. Thus, a major limitation of using symptomatic CAD endpoints (eg, sudden coronary death, myocardial infarction) as a study outcome is substantial disease misclassification. Coronary artery calcification (CAC) is part of the atherosclerotic process and is an independent predictor of CAD endpoints. In the present study, CAC was noninvasively quantified by electron beam computed tomography. We performed genome-wide multipoint mode-of-inheritance-free linkage analysis on affected sib pairs, defined as being ≥ the 70th sex- and age-specific percentile for CAC quantity, in a sample of 29 families enriched for hypertension. Almost 95% of participants were asymptomatic for CAD. Our LOD score (log10 odds in favor of linkage) results provide evidence that chromosomal regions 6p21.3 (maximum LOD score =2.22, P=0.00070) and 10q21.3 (maximum LOD score=3.24, P=0.000057) may harbor genes associated with subclinical coronary atherosclerosis.

Original languageEnglish (US)
Pages (from-to)418-423
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume22
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Atherosclerosis
  • Coronary artery calcification
  • Coronary artery disease
  • Electron beam computed tomography
  • Genome-wide scan

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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