Bivariate Whole Genome Linkage Analysis For Obesity And Osteoporosis

Obesity 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.Body fat mass,a component of body weight,is one of the most important indices of obesity,and a substantial body of evidence indicates that fat mass may have beneficial effects on bone.Contrasting studies,however,suggest that excessive fat mass may not protect against osteoporosis or osteoporotic fracture.Both diseases could share several common genetic and environmental factors.There are two goals of this study:the first is to determine the genetic,environmental and phenotypic correlations between BFM and BMD in 4498 Caucasian individuals from 451 families.The other is to identify systemically the shared genomic regions for BFM and BMD.We performed a quantitative genetic analysis and a bivariate whole-genome linkage scan for BFM and BMD at the hip, spine,and wrist,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 BFM and spine,hip,wrist BMD were significant(p＜0.001) ranging from 0.43 to 0.70.Correlations between BFM and spine, hip,wrist BMD also were significant which suggested that BMF and BMD are under strong genetic control.Furthermore,some common genetic and environmental factors are shared by BFM and BMD.Interestingly,it was found to significant genetic correlation difference between female and male.In the entire sample,suggestive linkages were detected at 7p22-p21 for BFM and spine BMD,6q27 for BFM and hip BMD,and 11q13 for BFM and wrist BMD.Male-specific suggestive linkages were found at 13q12 for BFM and spine BMD and at 7q21 for BFM and hip BMD.Female-specific suggestive linkage,was found at 15q13 for BFM and spine BMD.In a word,several shared genomic regions for BFM and BMD were identified here.Our data may benefit further positional and functional studies,aimed at eventually uncovering the complex mechanism underlying the shared genetic determination of obesity and osteoporosis.