Rare mutations Our group has been using the High Bone Mass Study to identify novel genetic causes of raised bone mineral density, with the aim of identifying targets for developing anabolic (bone-forming) treatments for osteoporosis. A recent highlight is the identification of SMAD 9 as novel genetic cause of High Bone Mass (ref: Pure/208990315). Having identified novel genes in this way, we have established a collaboration with Dr Chrissy Hammond’s laboratory to pursue functional studies in zebrafish.

Common genetic influences We have played a leading role in consortium-based genome wide association studies (GWAS), intended to identify common genetic influences on traits contributing to the risk of osteoarthritis and osteoporosis, such as hip shape (ref: Pubmed/29882636). We now plan to extend these studies based on novel DXA-derived phenotypes generated in UK Biobank as part of the AUGMENT study.

Mendelian randomisation studies We aim to examine causal pathways in musculoskeletal conditions, using Mendelian randomisation methods based on GWAS data, in collaboration with the MRC IEU. For example, we recently used a GWAS of circulating sclerostin to examine causal relationships between circulating sclerostin and osteoporosis risk (ref: Pubmed/31170332).