title: Genetic and phenotypic architecture of metabolic syndrome-associated components in dyslipidemic and normolipidemic subjects: the GEMS Study.
abstract: 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).
authors: World Wide Epidemiology, GlaxoSmithKline, Harlow, UK.
authors: Heide
authors: H
authors: Stirnadel
authors: Xiwu
authors: X
authors: Lin
authors: Hua
authors: H
authors: Ling
authors: Kijoung
authors: K
authors: Song
authors: Philip
authors: P
authors: Barter
authors: Y Antero
authors: YA
authors: Kesäniemi
authors: Robert
authors: R
authors: Mahley
authors: Ruth
authors: R
authors: McPherson
authors: Gérard
authors: G
authors: Waeber
authors: Thomas
authors: T
authors: Bersot
authors: Jonathan
authors: J
authors: Cohen
authors: Scott
authors: S
authors: Grundy
authors: Braxton
authors: B
authors: Mitchell
authors: Vincent
authors: V
authors: Mooser
authors: Dawn
authors: D
authors: Waterworth
mesh_terms: D000273:Adipose Tissue; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016000:Cluster Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D019655:Quantitative Trait, Heritable