Phenotypic, genetic, and genome-wide structure in the metabolic syndrome

Abstract

Background: Insulin resistance, obesity, dyslipidemia, and high blood pressure characterize the metabolic syndrome. In an effort to explore the utility of different multivariate methods of data reduction to better understand the genetic influences on the aggregation of metabolic syndrome phenotypes, we calculated phenotypic, genetic, and genome-wide LOD score correlation matrices using five traits (total cholesterol, high density lipoprotein cholesterol, triglycerides, systolic blood pressure, and body mass index) from the Framingham Heart Study data set prepared for the Genetic Analysis Workshop 13, clinic visits 10 and 1 for the original and offspring cohorts, respectively. We next applied factor analysis to summarize the relationship between these phenotypes.

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

“…The genetic and environmental correlations estimated from the present study are mostly in line with previous studies [12,[16][17][18][19][20][21]. Moderate correlations between insulinrelated endophenotypes and obesity traits have previously been reported [16,18,19].…”

“…These results indicate that phenotypic variation in individual endophenotypes is mostly due to genetic effects and this is consistent with the many univariate analyses published by us and others [9][10][11][12][13]23]. Environmental factors contributing to the variation of the endophenotypes between individuals appear to be mostly experienced by individuals and not shared between family members.…”

“…Those studies also reported that common environmental variance shared by family members did not contribute to the variations of the endophenotypes. Some family studies reported smaller genetic components influencing phenotypic variation in the phenotypes related to the metabolic syndrome [9,12,15,31], but the components were still significantly different from zero.…”

“…A wide range of heritabilities (mostly moderate to high) have been estimated for obesity traits (mean: 0.55; range: 0.37-0.80) [9][10][11][12][13][14]; insulin-related traits (mean: 0.38; range: 0.08-0.75) [9][10][11][13][14][15][16]; BP (mean: 0.41; range: 0.16-0.76) [9][10][11][12][13] and lipid traits (mean: 0.46; range: 0.20-0.70) [9][10][11][12][13]. However, the underlying mechanism of the clustering of these characteristics in an individual remains unclear [17].…”

“…Correlations between insulin-related endophenotypes and obesity endophenotypes have been previously estimated to be moderate or high [16,18,19], while correlations between other metabolic syndrome endophenotypes have been found to be weak or moderate [12,16,[19][20][21]. These correlations have surprisingly often been interpreted as strong evidence for a common factor underlying the metabolic syndrome.…”