Common familial influences on clustering of metabolic syndrome traits with central obesity and insulin resistance:: the Kiel obesity prevention study

Objective: The phenotypic heterogeneity of metabolic syndrome (MSX) suggests heterogeneity of the underlying genotype. The aim of the present study was to examine the common genetic background that contributes to the clustering between the two main features (insulin resistance, central obesity) and different MSX component traits. Methods: In all, 492 individuals from 90 families were investigated in a three-generation family path study as part of the Kiel Obesity Prevention Study (KOPS, 162 grandparents, 66.1 +/- 6.7 years, 173 parents, 41.3 +/- 5.4 years and 157 children, 10.8 +/- 3.4 years). Overall heritability was estimated and common familial (genetic and environmental) influences on insulin resistance (HOMA-IR) or central obesity (elevated waist circumference, WC), respectively, and different MSX traits were compared in a bivariate cross-trait correlation model. Results: Prevalence of MSX (according to NCEP criteria) was 27.2% (f) and 27.8% (m) in adults and 3.5% (f) and 8.5% (m) in children and adolescents, respectively. MSX phenotype was found to be highly variable, comprising 16 subtypes of component trait combinations. Within-trait heritability was 38.5% for HOMA-IR and 53.5% for WC, cross-trait heritability was 53.4%. As much as 6-18% and 3-10% of the shared variance between different MSX component traits (lipid profile, blood pressure) and WC or HOMA-IR, respectively, may be genetic. With the exception of HDL-C, the shared genetic variance between MSX component traits and WC was higher than the genetic variance shared with HOMA-IR. Conclusion: A common genetic background contributes to the clustering of different MSX component traits and central obesity or insulin resistance. Common genetic influences favour central obesity as a major characteristic linking these traits.