TY - JOUR
T1 - Genomic loci with pleiotropic effects on coronary artery calcification
AU - Turner, Stephen T.
AU - Peyser, Patricia A.
AU - Kardia, Sharon L.R.
AU - Bielak, Lawrence F.
AU - Sheedy, Patrick F.
AU - Boerwinkle, Eric
AU - De Andrade, Mariza
N1 - Funding Information:
This work was supported by United States Public Health Service Grants from the National Institutes of Health U01 HL 54464, U01 HL 54457, U01 HL 54481, R01 HL 71917, and M01 RR 00585. We appreciate the technical assistance provided by Curtis Olswold, Tracy Fuller, Jeremy Palbicki, and Jodie Van De Rostyne.
PY - 2006/4
Y1 - 2006/4
N2 - 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) ≥ 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.
AB - 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) ≥ 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.
KW - Blood pressure
KW - Coronary artery calcification
KW - Coronary artery disease
KW - Genetic linkage
KW - High-density lipoprotein-cholesterol
KW - Multivariate
KW - Obesity
KW - Pulse pressure
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U2 - 10.1016/j.atherosclerosis.2005.06.010
DO - 10.1016/j.atherosclerosis.2005.06.010
M3 - Article
C2 - 16054150
AN - SCOPUS:33644520868
SN - 0021-9150
VL - 185
SP - 340
EP - 346
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -