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

Abstract

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.

An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample

“…( 37 ) In line with the significant genetic correlation between LM and FM ( r g = 0.29) in this study, a bivariate linkage analysis also suggests several genomic regions (20p12, 3p26-25, and Xp22) that may jointly influence FM and LM. ( 39 ) The results of this study differ from those of Nguyen and colleagues,( 15 ) who examined the relationships among LM, FM, and BMD in Australian female twins. In their study, the genetic correlation between LM and whole-body BMD was 0.09 and nonsignificant.…”

Differences in fat and muscle mass associated with a functional human polymorphism in a post‐transcriptional BMP2 gene regulatory element

“…For example, although the overall mass of soft tissue comprised of fat and muscle positively correlates with bone mass [Reid, 2002], the genetics of this relationship is highly complex and is influenced by sex, age, and environment [Karasik and Kiel, 2008]. Recently, an analysis of 420 pedigrees identified a quantitative trait locus on chromosome 20 (20p12-11) with a LOD score of 2.04 that influenced both total body fat mass and total body lean mass [Zhao et al, 2008]. The 20p12-11 region includes the BMP2 gene.…”

“…Recently BMP2 was shown to up-regulate sets of inhibitory microRNAs that suppress myogenesis and to down-regulate sets of microRNAs that inhibit osteogenesis [Li et al, 2008]. Genetic associations between the BMP2 gene and several bone and soft tissue parameters have been reported [Styrkarsdottir et al, 2003; Reneland et al, 2005; Xiong et al, 2006; McGuigan et al, 2007, 2008; Tranah et al, 2008; Zhao et al, 2008]. Thus, it is reasonable to postulate that BMP2 levels influence the allocation of cells to bone, cartilage, fat, or muscle during embryonic or post-natal development or in response to exercise.…”

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments

“…[12][13][14]16,17 The main results from this study suggest that carriers of PCK1 rs11552145-AA genotype have lower BMI when compared to G-allele carriers in psychiatric patients treated with weight gain inducing drugs, this association being found in the discovery sample and in the replication samples analyzed together. Moreover, low WC and TG levels were associated with rs11552145-AA in the discovery sample, and low BMI and WC were found as well for rs2071023-CC genotype.…”

“…14 This is in line with the positive correlation found between PCK1 mRNA expression levels and body mass index (BMI), body fat percentage, TG, and CHOL levels in subcutaneous adipose tissue of nonmenopausal women. 15 In humans, regions near PCK1 locus have been related to obesity or fat mass, 16,17 and several positive associations have been reported between PCK1 polymorphisms and type 2 diabetes mellitus (T2DM) [18][19][20] although these results could not always be replicated. 21 Other studies conducted in the general population showed no significant association between PCK1 polymorphisms and BMI, WC or physical activity.…”