GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
How Does Disruption Of Circadian Rhythms Induce Diabetes?
Funder
National Health and Medical Research Council
Funding Amount
$631,782.00
Summary
Increasing evidence suggests that disturbed circadian rhythms initiate and amplify metabolic and cardiovascular disease. The increasing and already high proportion of workers engaged in shiftwork, and increased frequency of disruption of these rhythms in the population more generally, implicate this body system as contributing to the growing epidemic of obesity and diabetes and related disorders in our community and world-wide. While we are now beginning to understand how our rhythms are synchro ....Increasing evidence suggests that disturbed circadian rhythms initiate and amplify metabolic and cardiovascular disease. The increasing and already high proportion of workers engaged in shiftwork, and increased frequency of disruption of these rhythms in the population more generally, implicate this body system as contributing to the growing epidemic of obesity and diabetes and related disorders in our community and world-wide. While we are now beginning to understand how our rhythms are synchronised to night and day, how this rhythmicity is linked to our organs in the normal and common disease states such as diabetes is poorly understood. The discovery of a special set of genes, called clock genes that function in all of the cells in our bodies and strongly influence the function of our organs such as the liver, pancreas and heart has been particularly important. We hypothesise that both environmentally (exogenous) and genetically (endogenous) induced disruption of circadian rhythms causes metabolic dysfunction. This is due to altered central and peripheral clock gene expression rhythms, which in turn alter metabolic rhythms and impair glucose homeostasis. This project aims to determine the impact of disrupted rhythmicity on metabolism with a particular emphasis on the possibility that the disrupted rhythmicity may be a predisposing factor for the development of diabetes.Read moreRead less