TY - JOUR
T1 - Genetic and phenotypic architecture of metabolic syndrome-associated components in dyslipidemic and normolipidemic subjects
T2 - The GEMS Study
AU - Stirnadel, Heide
AU - Lin, Xiwu
AU - Ling, Hua
AU - Song, Kijoung
AU - Barter, Philip
AU - Kesäniemi, Y. Antero
AU - Mahley, Robert
AU - McPherson, Ruth
AU - Waeber, Gérard
AU - Bersot, Thomas
AU - Cohen, Jonathan C
AU - Grundy, Scott M
AU - Mitchell, Braxton
AU - Mooser, Vincent
AU - Waterworth, Dawn
PY - 2008/4
Y1 - 2008/4
N2 - Atherogenic dyslipidemia, manifest by low HDL-cholesterol and high TG levels, is an important component of ATP-III defined metabolic syndrome. Here, we dissected the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipo-cytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size, in a large family data set (n = 2800) and in an independent set of dyslipidemic cases (n = 716) and normolipidemic controls (n = 1073). We explored the relationships among these phenotypes using variable clustering and then estimated their genetic heritabilities and cross-trait correlations. In families, four clusters explained 61% of the total variance, with one adiposity-related cluster (including hsCRP), one BP-related cluster, and two lipid-related clusters (HDL-C, TG, adiponectin and LDL particle size; apoB and non-HDL-C). A similar structure was observed in dyslipidemic cases and normolipidemic controls. The genetic correlations in the families largely paralleled the phenotype clustering results, suggesting that common genes having pleiotropic effects contributed to the correlations observed. In summary, our analyses support a model of metabolic syndrome with two major components, body fat and lipids, each with two subcomponents, and quantifies their degree of overlap with each other and with metabolic-syndrome related measures (adipokines, LDL particle size and hsCRP).
AB - Atherogenic dyslipidemia, manifest by low HDL-cholesterol and high TG levels, is an important component of ATP-III defined metabolic syndrome. Here, we dissected the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipo-cytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size, in a large family data set (n = 2800) and in an independent set of dyslipidemic cases (n = 716) and normolipidemic controls (n = 1073). We explored the relationships among these phenotypes using variable clustering and then estimated their genetic heritabilities and cross-trait correlations. In families, four clusters explained 61% of the total variance, with one adiposity-related cluster (including hsCRP), one BP-related cluster, and two lipid-related clusters (HDL-C, TG, adiponectin and LDL particle size; apoB and non-HDL-C). A similar structure was observed in dyslipidemic cases and normolipidemic controls. The genetic correlations in the families largely paralleled the phenotype clustering results, suggesting that common genes having pleiotropic effects contributed to the correlations observed. In summary, our analyses support a model of metabolic syndrome with two major components, body fat and lipids, each with two subcomponents, and quantifies their degree of overlap with each other and with metabolic-syndrome related measures (adipokines, LDL particle size and hsCRP).
KW - Cardiovascular diseases
KW - Diabetes mellitus, type 2
KW - Hyperlipidemia
KW - Lipoproteins
KW - Metabolic syndrome X
UR - http://www.scopus.com/inward/record.url?scp=40949107647&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40949107647&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2007.07.038
DO - 10.1016/j.atherosclerosis.2007.07.038
M3 - Article
C2 - 17888929
AN - SCOPUS:40949107647
SN - 0021-9150
VL - 197
SP - 868
EP - 876
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -