[Genome-wide association study for Osteoporosis]

Numerous studies on genetic risks for osteoporosis have been performed to date, mainly using genome-wide association studies(GWAS)for assessing bone mineral density(BMD)as a quantitative trait, and recent large-scale meta-analyses of GWAS have identified a number of single nucleotide polymorphisms(SNPs)associated with low BMD or increased risk of fracture. Several of these SNPs cluster within the RANK signaling, mesenchymal stem cell differentiation, endochondral ossification, and Wnt signaling pathways. GWAS performed in Japanese populations also identified novel osteoporosis susceptibility genes such as FONG, WDSOF1 and GPR98. It is estimated that previously identified loci associated with BMD in total explain ~5%of the genetic variance for this trait. Some genetic risk scores based on BMD-decreasing alleles of the SNPs have been developed, however, their prediction ability for the risk of osteoporosis and fracture appears to be limited when BMD is known.