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Familial Aggregation and Genome-Wide Linkage Analysis of Carotid Artery Plaque: The NHLBI Family Heart StudyPankow J.S.a · Heiss G.b · Evans G.W.d · Sholinsky P.e · Province M.A.f · Coon H.g · Ellison R.C.h · Miller M.B.a · Qaqish B.c
aDivision of Epidemiology, University of Minnesota, Minneapolis, Minn., Departments of bEpidemiology and cBiostatistics, University of North Carolina, Chapel Hill, N.C., dDepartment of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, N.C., eEpidemiology and Biometry Program, National Heart, Lung and Blood Institute, Bethesda, Md., fDivision of Biostatistics, Washington University, St. Louis, Mo., gDepartment of Psychiatry, University of Utah, Salt Lake City, Utah, hSection of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Mass., USA
Objective: To evaluate familial and genetic influences on carotid artery plaque, a qualitative marker of the systemic burden of atherosclerosis. Methods: The design was a cross-sectional study of 2,223 members of 525 randomly-ascertained families and 2,514 members of 589 high coronary heart disease (CHD) risk families from 4 U.S. communities. Results: The prevalence of plaque was 33, 36, and 47%, respectively, among probands with 0, 1, and 2 or more first-degree relatives with a history of CHD. There was evidence of sibling aggregation of plaque in random families (OR = 1.89; 95% CI: 1.44, 2.48), but associations were substantially attenuated when adjusted for major cardiovascular disease risk factors. A genome scan with 420 microsatellite markers revealed no regions of significant or suggestive linkage for plaque in 342 affected sibling pairs, although suggestive linkage (LOD score: 2.43) was found on chromosome 2p11.2 (D2S1790) in pairs aged 55 years or younger. Other markers with nominal evidence for linkage (p < 0.05) were found on chromosomes 2p25, 2q24-q32, 6q21-q23, 7p12-p21, 7q11-q21, 8q24, 12q12-q13, 18p11, 21q21 and Xp11, Xq12, and Xq24. Conclusions: There was modest familial aggregation of carotid artery plaque, but a genome-wide scan indicated no regions of significant or suggestive linkage.
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