Genetic and phenotypic architecture of metabolic syndrome-associated components

Atherogenic dyslipidaemia is defined by low HDL-cholesterol and high triglyceride (TG) levels. The aim of the current study was to dissect the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipocytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size. A large family data set and an independent set of dyslipidaemic cases and normolipidaemic controls were used. Among families, four clusters explained 61% of the total variance, with one adiposity-related cluster, one BP-related cluster, and two lipid-related clusters. A similar structure was observed in dyslipidaemic cases and normolipidaemic controls. The variable clustering analysis identified two major domains of metabolic syndrome, one associated with adiposity and another primarily lipid-related. Adiponectin was found to fall into the lipid cluster, while leptin was associated with the body fat component. The genetic correlations in the families largely paralleled the phenotype clustering data, suggesting that common genes having pleiotropic effects contributed to the correlations observed.

Abstract

Keywords:
Adipokine – Adipose tissue – Atherogenic dyslipidaemia – Blood pressure – CRP – LDL particle size – Leptin – Metabolic syndrome