It induces expression of the intestinal alkaline phosphatase gene and inhibits beta-catenin/T-cell factor transcriptional activity [30]. The functional significance of Homeobox (Hox) genes in embryonic skeletogenesis has been well documented by knockout and deficiency studies; Hox gene expression is reactivated during bone regeneration. The presence of putative Cdx1-binding sites within the regulatory sequences of Hox genes and in vitro transactivation of Hoxa-7 by Cdx1 indicates a direct interaction [31, 32]. Further

replication and functional analyses are required to confirm the hypothesis that there is a direct regulation BIRB 796 cell line between CDX1-binding and the expression level of POSTN. Our comprehensive imputation-based analysis identified rs9547970 as the variant that best explains the observed association in this study. Although most promising as the causal variant, it is also

possible that rs9547970 is in LD with other unobserved and independent functional variants. According to CUDC-907 supplier the imputation based analysis, there was no strong evidence to support this, although the possibility of other independent rare variants of MAF <0.01 in the POSTN gene cannot be ruled out. Resequencing of the entire gene in a large number of individuals would provide more information to clarify the association of the POSTN gene with osteoporosis risk. Our findings were not observed in recently reported GWAS in Caucasian populations [33–35]. This may be due to ethnic differences and sampling and statistical methods. Nevertheless, our study sample was selected from a large population with relatively high homogeneity. The selected sampling strategy can substantially increase power over random sampling for detection of allelic association [36]. According to the Genetic Power Calculator [37], our HKSC extreme cohort has more than 95% power to detect an association for Nitroxoline a functional locus accounting for 1% phenotypic variation (P = 0.002, MAF = 0.3,

D′ = 0.8). Moreover, the identified association was replicated in another independent population using different genotyping technique and sampling selleck chemicals method. Although GWAS are clearly a major advance for gene discovery, the results from those studies also suggest that more osteoporosis-related variants and genes are yet to be discovered. To date, confirmed loci account for <5% of the BMD variation in the general population, leaving heritability largely unexplained. Many more common variants with increasingly smaller effects and rare variants with possible large effects could contribute to the undiscovered genetic component. In addition, the gene–gene interactions are acknowledged as important contributors to genetic variation in human complex traits. The functional study in animal mode demonstrated that the matricelluar Postn protein is required for Sost inhibition and thereby plays an important role in the determination of bone mass and microstructural [14].