Contribution of body composition components and soft-tissue biochemical factors to genetic variation of body mass index (BMI) in an ethnically homogeneous population

OBJECTIVES: Elevated BMI results from an excess of not only fat mass (FM) but also fat-free soft tissue mass (FFM). Both components of body soft tissue, FM, and FFM, are now considered as active endocrine organs. The major aim of this study was to explore the genetic architecture of BMI, considering genetic variations of its major soft tissue components, and the main biochemical factors associated with their corresponding metabolism: leptin, adiponectin, E-selectin, and insulin-like growth factor binding protein, IGFBP-1.

METHODS: A total of 1,502 apparently healthy individuals (783 men, 719 women) from 359 ethnically homogeneous families were assessed anthropometrically for body composition. Model-based quantitative genetic analyses were implemented to reveal genetic and shared environmental factors affecting the variation and covariation of the studied phenotypes.

RESULTS: We found that inter-individual variation in BMI is strongly correlated with both body composition components (r > 0.92, P < 0.001). These correlations are caused by shared genetic and environmental factors that were interpreted to be a direct result of the intimate genetic and environmental correlations between FM and FFM. The latter were also significantly correlated with leptin, E-selectin, and IGFBP-1. However, whereas leptin displayed both genetic and environmental correlations with both FM and FFM, their correlations with E-selectin were caused only by common genes, and with IGFBP-1-only by a shared environment.

CONCLUSIONS: This study clearly suggests that FM and FFM contributed almost equally to BMI variation, and provides evidence that this contribution is caused by common genetic as well as shared environmental and metabolic factors.