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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:418.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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, II; Eric Boerwinkle; Patricia A. Peyser

From the Sections on Epidemiology and Biostatistics (L.A.L., E.M.L., C.D.L.), Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC; the Department of Epidemiology (L.F.B., S.L.K., P.A.P.), School of Public Health, University of Michigan, Ann Arbor; the Medical Research Council Clinical Trials Unit (P.R.), London, UK; the Division of Hypertension and Department of Internal Medicine (S.T.T.) and Department of Diagnostic Radiology (P.F.S.), Mayo Clinic and Foundation, Rochester, Minn; and the Human Genetics Center and Institute of Molecular Medicine (E.B.), University of Texas Houston Health Science Center, Houston.

Correspondence to P. Peyser, PhD, School of Public Health, University of Michigan, 109 Observatory, Ann Arbor, MI 48109-2029. E-mail ppeyser{at}umich.edu

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.

Key Words: atherosclerosis • coronary artery disease • coronary artery calcification • electron beam computed tomography • genome-wide scan

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