b Inference of gene regulatory networks using hip BMD genes
Discussion GWA is a powerful tool that can identify genes associated with common diseases or traits such as BMD variation. Nonetheless, GWA studies usually focus on the most significant individual variants without considering the global evidence of the gene tested. It should be noted that allelic heterogeneity (i.e., presence of more than one susceptibility allele in a locus or gene) greatly reduces the power for testing of an individual SNP [7, 8]. Therefore, a gene-based test can ameliorate the situation by simply testing the global null hypothesis about the SNPs located per gene. The gene-based test is a direct and powerful means of protecting the overall false-positive rate when a collection of loci are tested, because the p value from the gene-based test has already corrected the number of SNPs included via a simulation approach. Using gene-based analysis selleck chemical of GWA data, our study confirmed several well established candidate genes and suggested several novel genes and loci for BMD variation. this website Importantly, most of these genes did not contain any SNP that reached genome-wide significance, so the potential importance of these genes would not have been recognized in the absence of gene-based association study. An ethnic-specific BMD gene may underlie BMD variation in southern Chinese and
Europeans. In line with the observations of our recent GWAS, there was no overlap of genes in the significant or suggestive gene list from HKSC and dCG populations We recently identified a SNP rs2273601 in JAG1 that was associated with spine BMD (p value = 1.06 × 10−8) in 1,520 HKSC subjects with extreme BMD; nonetheless, only a modest association of this SNP with spine BMD was observed in three Caucasian cohorts (p range, 0.007–0.045) . In the current study, we observed that top hip BMD genes were more consistent in HKSC and dCG, as reflected by the inflation factor and the results from independent t testing (Supplementary methods, Supplementary Figures 3 to 4, and Supplementary Table 2). The discrepancies of gene-based association results for spine click here BMD in two populations
may be due to a number of factors such as lifestyle, diet, and genetic background. Although these factors may also affect hip BMD, the possibility that spine BMD may be more susceptible than hip BMD to gene and environment interaction cannot be excluded. If this hypothesis is true, identification of gene and environmental interaction will www.selleckchem.com/products/bay80-6946.html benefit genetic research into osteoporosis and clinical practice. The study design of HKSC and dCG also differed. In our HKSC cohort, we studied subjects at the extremes of BMD distribution. Studying subjects at the extremes of a quantitative phenotype has proven useful in identifying functional rare variants [9, 10]. The genes identified in our HKSC cohort may therefore harbor more rare variants than the dCG cohort.