Dr. John Kemp

Genetic Determinants of Bone Mineral Density and Osteoporosis

I am interested in identifying genetic factors that influence bone traits. Bone mineral density (BMD) is a particularly interesting bone phenotype that serves as a good predictor of bone strength and fracture risk and consequentially is used as the primary diagnostic marker for osteoporosis. Twin and family studies suggest that BMD is highly heritable, indicating that genetic elements are partly responsible for variation in fracture risk (FR) and osteoporosis. In an attempt to better understand the genetic variation underlying osteoporosis, large scale genome-wide association studies (GWAS) have recently identified more than 56 genetic loci associated with BMD. However, despite this success, these known genetic variants only explain a small proportion of the estimated heritability of BMD (i.e. ~5.8%). This discrepancy implies that there are many more genetic variants underlying BMD that remain to be discovered. Thus the current challenge facing the field of bone genetics is to determine the location of this unexplained heritability as these variants may provide substantial insight into the aetiology of osteoporosis. BMD is influenced by: i) the acquisition of bone mass during childhood, adolescence and young adulthood ii) the subsequent maintenance of bone mass over the life course and iii) the progressive loss of bone mass in later life. It is therefore conceivable that the genetic variants may exert age dependent effects on BMD, depending on whether the genetic variant effects bone acquisition, maintenance and/or loss. To date, most GWAS studies have focused on BMD measures of late adulthood and have largely ignored pediatric measures. For this reason, I together with members of the Avon Longitudinal Study of Parents and Children (ALSPAC, University of Bristol, UK) and the University of Queensland Diamantina Institute (UQDI, Australia), aim to investigate paediatric and adolescent BMD to identify genetic and other environmental risk factors that primarily influence bone acquisition. To date, we have identified several novel paediatric BMD associated loci and are in the process of recruiting additional cohorts in an effort to expand our study.