Bivariate Whole Genome Linkage Analysis for Bone and Muscle
|School||Hunan Normal University|
|Keywords||Sarcopenia Lean body weight Osteoporosis Bone density Heritability Genetic correlation Related to the environment Whole genome Bivariate linkage analysis|
With the extension of life expectancy and the aging of society, osteoporosis has become one of the serious diseases affecting human health and quality of life. Recent studies have found that skeletal muscle with aging changes that sarcopenia is one of the important factors to promote the development of osteoporosis and serious consequences. Sarcopenia and osteoporosis are common have a great impact on human health, the complexity of human disease, they are well received by the decision of the genetic and environmental factors influence and between environmental and genetic and gene interaction role. Whole body lean body mass and bone mineral density were sarcopenia and osteoporosis are two important phenotype. Muscle and bone to form a whole, the muscle strength changes in bone strength will cause a corresponding change. But the common genetic basis for the study of bones and muscles are still relatively few. The main purpose of this study: on the one hand, in a total of 4498 Caucasian sample of the 451 nuclear pedigrees, genetic analysis of single-factor analysis of variance estimated lean body weight (TBLM) and waist, hip bone mineral density (BMD) in the narrow sense heritability (h ~ 2), and by the bivariate analysis of variance to estimate the genetic, environmental and phenotypic correlations between TBLM and different parts of BMD; through the whole body lean body mass and bone mineral density bivariate genome-wide linkage scan (WGLS ) analysis finding and found to affect both TBLM and BMD QTL loci and the detection and analysis of gene pleiotropic (single locus affects multiple traits) and chain signal close to effect (closely linked to multiple sites were affected differently traits). Take into account the impact of the sex-specific, we still made the above analysis in general, men and women in the sample group. Genetic decisive analysis showed that the overall sample and the male and female samples, TBLM and waist and hip BMD significantly (p <0.001), genetic rate from 0.51 to 0.71. In the sample group TBLM waist, hip BMD between genetic, environmental and phenotypic parameters show a significant correlation, indicating that genetic and environmental related TBLM and between different parts of the BMD, further suggests that there may be some sharing of genetic and environmental factors TBLM with BMD between. At the same time, we found that male and female samples of between TBLM and waist and hip BMD genetic correlation between the presence of differences that may exist between men and women different QTL sites at the same time to affect TBLM and BMD. According to the results of the analysis of TBLM and BMD, further, in general, men and women in the sample group to made TBLM and waist, hip BMD bivariate genome-wide linkage analysis. In the female sample, we found that the presence of chromosome 15q13 region significantly with the chain of signals affect TBLM and lumbar BMD, chromosome 7q32 region exists recommended chain signals affect TBLM and lumbar BMD, TBLM and hip BMD; overall sample, we found that chromosome 7p22 regional the recommendations chain the signal affect TBLM and lumbar BMD; male samples, we found that the region of chromosome 7q21, 13p11 region exists proposed linkage signal respectively the impact TBLM and hip BMD TBLM, and lumbar BMD. Linkage analysis of X chromosome two points also suggest the Xq25 regional presence of significant linkage signal. On chromosome 7q32 and 13p11 region may exist impact TBLM and lumbar BMD the TBLM and hip BMD fully Gene pleiotropic chromosome 7p22 region the impact TBLM and lumbar BMD complete linkage signal near effect may exist. Overall, this study verified the bones and muscles of genetic, environmental and phenotypic related positioning a number of chromosomal regions linkage signal at the same time to affect TBLM and BMD, and detected the presence of pleiotropy and linkage signal close to effect chromosomal region. The foundation of our research sarcopenia and osteoporosis in the future functional studies and molecular mechanism of their common genetic determinants.