Genetic effects on bone health

In recent years, the lower costs of arrays and sequencing technologies, and the better availability of data from genome-wide association studies (GWASs) have led to more reports on genetic factors that are associated with bone health. However, there remains the need for a summary of the newly identified genetic targets that are associated with bone metabolism, and the status of their functional characterization.

GWASs revealed dozens of novel genetic loci that are associated with bone mineral density (BMD). Some of these targets have been functionally characterized, although the vast majority have not. Glypican 6, a membrane surface proteoglycan involved in cellular growth control and differentiation, was identified as a novel determinant of BMD and represents a possible drug target for treatment of osteoporosis. Pathway analysis also showed that cell-growth pathways and the SMAD proteins associated with low BMD.

Hits that were significantly associated with BMD in different studies represent likely candidates (e.g. SOST, WNT16, ESR1 and RANKL) for functional characterization and development of osteoporosis treatments. Indeed, currently available treatment for osteoporosis (antibody against RANKL) appeared a significant target in four recent GWAS studies indicating their applicability and importance for future treatment development.