Familial aggregation and genome-wide linkage analysis of carotid artery plaque: the NHLBI family heart study.
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.
Pankow
James S
JS
Division of Epidemiology, University of Minnesota, 1300 South Second Street, Ste. 300, Minneapolis, MN 55454, USA. pankow@epi.umn.edu
Heiss
Gerardo
G
Evans
Gregory W
GW
Sholinsky
Phyliss
P
Province
Michael A
MA
Coon
Hilary
H
Ellison
R Curtis
RC
Miller
Michael B
MB
Qaqish
Bahjat
B
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000235:genetics; D016893:Carotid Stenosis / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
D005819:Genetic Markers