Genomic loci with pleiotropic effects on coronary artery calcification.
We measured 381 genomewide markers and performed genetic linkage analyses in search of loci influencing coronary artery calcification (CAC), a measure of atherosclerosis determined by electron beam computed tomography, in 948 non-Hispanic white siblings (mean age [+/-standard deviation] = 59.6 +/- 9.9 years; 73.7% hypertensive). Measured risk factors for atherosclerosis included body mass index, pulse pressure, and high-density lipoprotein (HDL)-cholesterol. After adjustment for sex and age, the logarithm transformed measure of CAC was heritable (0.40 +/- 0.08, P < 0.0001) and genetically correlated with body mass index (0.28, P < 0.001), pulse pressure (0.36, P < 0.001), and HDL-cholesterol (-0.19, P < 0.001). Univariate linkage analysis demonstrated evidence of linkage for CAC, defined by maximum LOD scores (MLS) >or= 1.30, on chromosomes 1p, 4p, 5q, 7p, 13q, and 14q. Bivariate linkage analyses of CAC with each risk factor provided evidence of two regions with pleiotropic effects on CAC and HDL-cholesterol on chromosomes 4p16 (MLS=3.03, P = 0.00084) and 9q12 (MLS = 3.21, P = 0.00056), and of a region with pleiotropic effects on CAC and body mass index on chromosome 17p11 (MLS = 3.04, P = 0.00082). Inasmuch as the chromosome 9 and 17 regions were not detected in the univariate linkage analysis for CAC, multivariate linkage analyses of CAC and genetically correlated risk factors may help localize genes for coronary atherosclerosis.
Turner
Stephen T
ST
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. turner.stephen@mayo.edu
Peyser
Patricia A
PA
Kardia
Sharon L R
SL
Bielak
Lawrence F
LF
Sheedy
Patrick F
PF
Boerwinkle
Eric
E
de Andrade
Mariza
M
D001794:Blood Pressure; D015992:Body Mass Index; D002114:Calcinosis / Q000235:genetics* / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci / Q000235:genetics*; D012307:Risk Factors
D008076:Cholesterol, HDL