Bivariate Whole Genome Linkage Analysis For Bone And Muscle

Osteoporosis has been one of the important diseases that serirously influence health and quality of life of human beings with the prolonging people's average life and social aging.Recent experimental results have demonstrated that skeletal muscle reduce with ageing(sarcopenia)is one of the most important factor behind osteoporosis.Sarcopenia and osteoporosis are two of the most important complex diseases that cause major public health problems.Both are the polygenic and complex disorder arising from the genetic and environmental factors,as well as the interactions between them.Whole body lean mass and bone mineral density are Sarcopenia and osteoporosis's key phenotypes,respectively. Muscle and bone are of one system,the changing of muscle is accompanied by variation of bone strength.Yet little is know about the common hereditary mechanism shared by them.There are two goals of this study:the first is to determine the genetic, environmental and phenotypic correlations between TBLM and BMD in 4498 Caucasian individuals from 451 families.The other is to identify systemically the shared genomic regions for TBLM and BMD.We performed a quantitative genetic analysis and a bivariate whole-genome linkage scan for TBLM and BMD at the hip,and spine,respectively. Correlation and Linkage analyses were performed in the total sample and the male and female subgroups,respectively.Univariate genetic analysis showed that the heritabilities(h~2)for TBLM and spine,hip BMD were significant(p＜0.001)ranging from 0.51 to 0.71.Correlations between TBLM and spine,hip BMD also were significant which suggested that TBLM and BMD are under strong genetic control.Furthermore,some common genetic and environmental factors are shared by TBLM and BMD.Interestingly,it was found to significant genetic correlation difference between female and male. Multipoint bivariate linkage analyses for 22 autosomes showed evidence of significant linkage with an LOD score of 4.86 at chromosome region 15q13 for TBLM & spine BMD in females,and suggestive linkage findings(LOD＞2.2)at 7p22 for TBLM & spine BMD for the entire sample,at 7q32 for TBLM & BMD at both spine and hip in the females, and for 7q21 and 13p11 for TBLM & BMD at both spine and hip in the males.Two-point linkage analyses for chromosome X also showed significant linkage signals at several regions such as Xq25.Complete pleiotropy(a single locus influencing both traits)was suggested at 7q32 and 13q11 for TBLM and BMD.Additionally,complete co-incident linkage(separate tightly clustered loci each influencing a single trait)was detected at 7p22 for TBLM and spine BMD.In a word,we identified several genomic regions shared by TBLM and BMD in Caucasians.Further studies may focus on fine mapping and identification of the specific QTLs in these candidate genomic regions.