Genetics of Osteoporosis : Meeting Report from the 31 st Annual Meeting of the American Society for Bone and Mineral Research September 11 - 15 , 2009 in Denver , Colorado

At this year’s meeting, the GWA study approach used to identify genes contributing to bone mineral density (BMD) and fracture risk attracted attention. BMD has been identified as the major risk factor for susceptibility to osteoporotic fractures and is currently the predominant study phenotype for osteoporosis. For example, using the dense Affymetrix 500K SNP gene chip method, two genes, parathyroid hormone (PTH) and interleukin 21 receptor (IL21R) were found to be associated with femoral neck BMD in two independent Caucasian samples (1). In another GWA study, SNPs in the cation channel, sperm-associated, beta (CATSPERB) and ADAM metallopeptidase with thrombospondin type 1 motif, 18 (ADAMTS18) genes provided evidence of association with femoral neck BMD (2). Interestingly, ADAMTS18 was previously found to be associated with hip BMD in an independent GWA study (3). Associations of several other polymorphisms with BMD in previous GWA studies, e.g., SNPs from catenin beta like 1 (CTNNBL1), low density lipoprotein receptor-related protein 5 (LRP5), osterix and intergenic regions on chromosomes 2 and 4, were replicated in younger American men and women (4). Based on an Efficient Mixed-Model Association algorithm, one study (5) performed a GWA analysis for BMD and gene expression values using expression SNPs (eSNPs) in the Hybrid Mouse Diversity Panel (HMDP), and identified a novel candidate gene named additional sex combs like 2 (ASXL2) for BMD. Besides SNPs, longer sequences of DNA insertions and deletions collectively called copy number variants (CNVs) are also rich and important markers for human diseases. At this year's meeting, one genome-wide CNV association study on osteoporosis found a CNV in one novel gene, vacuolar protein sorting 13 homolog B (VPS13B), associated with spine, hip and femoral neck BMD and cross-sectional area, cortical thickness and buckling ratio (6).