Bivariate genome linkage analysis suggests pleiotropic effects on chromosomes 20p and 3p for body fat mass and lean mass.

Total body fat mass (TBFM) and total body lean mass (TBLM) are the major components of the human body. Although these highly correlated phenotypic traits are frequently used to characterize obesity, the specific shared genetic factors that influence both traits remain largely unknown. Our study was aimed at identifying common quantitative trait loci (QTLs) contributing to both TBFM and TBLM. We performed a whole genome-linkage scan study in a large sample of 3255 subjects from 420 Caucasian pedigrees. Bivariate linkage analysis was carried out in both the entire sample and gender-specific subsamples. Several potentially important genomic regions that may harbour QTLs important for TBFM and TBLM were identified. For example, 20p12-11 achieved a LOD score of 2.04 in the entire sample and, in the male subsample, two genomic regions, 20p12 (LOD=2.08) and 3p26-25 (LOD=1.92), showed suggestive linkage. In addition, two-point linkage analyses for chromosome X showed suggestive linkages on Xp22 in the entire sample (LOD=2.14) and significant linkage on Xp22 in the female subsample (LOD=3.05). Complete pleiotropy was suggested for 20p12 and 3p26-25 in males. Our results suggest that QTLs on chromosomes 20p12, 3p26-25 and Xp22 may jointly influence TBFM and TBLM. Further fine mapping and gene identification studies for these pleiotropic effects are needed.