My research work is primarily based at the Garvan Institute of Medical Research's Bone Biology Division. I pursue both epidemiological and genetic research, often combining the two, to address issues that are transformational, shaping policy and practice leading to better treatment and control of osteoporosis.
In plain language, I want to find out why people have osteoporosis, what causes bone fracture, and how to predict the risk of fracture for an individual. My research program is driven by the hypothesis that an individual's susceptibility to fracture is determined by reduced bone strength due to bone loss, and deteriorated bone structure, and that bone loss and bone structure are primarily determined by genetic factors. Thus, my research objectives are: (a) to identify etiological factors and genes that are associated with bone loss and bone structure; and (b) to develop predictive models based on etiological and genetic factors to predict an individual's risk of fracture and adverse outcomes, especially mortality following a fracture.
In recent years, with the ongoing developments of high throughput sequencing technologies and advancement of modern bioinformatics, my research interests focus on the use of new technologies to discover genetic variants relevant to bone phenotypes and bone loss, and then translate the findings into personalised risk assessment. Key research areas include genome-wide sequencing studies of bone loss and bone fracture, and application of modern biostatistical methods to large clinical and genomic datasets. I am also interested in the dissection of the complex interrelationship between osteoporosis and diseases such as obesity, diabetes, cardiovascular disease, osteoarthritis and cancer.
My ongoing project: "diseasome"
People with osteoporosis are commonly found to have coexisting diseases (comorbidities), including diabetes, obesity, cardiovascular diseases, osteoarthritis and neurological disorders. On average, a person with osteoporosis has three co-diseases, the presence of which contributes to worsen the person’s bone health. The cumulative associations between these diseases could also increase the risk of mortality among patients with a fracture. While the presence of these comorbidities influences clinical decisions, the recognition of the role of comorbidities in fracture risk assessment has largely been ignored.
Professor Tuan Nguyen and his team are looking at the relationships between osteoporosis and the various illnesses that co-exist with it.
‘Many of these diseases are related through common genetic factors and environmental exposure,’ he said. ‘We think that osteoporosis and its multimorbidities share genes, proteins and pathways and tend to occur together at the same time.’
The ‘Diseasome of Osteoporosis’ project aims to construct a network map of comorbidities associated with osteoporosis and determine shared risk factors, environments and genetics, for co-occurrence of diseases. This project makes use of advances in the new scientific disciplines involving network medicine, genomes and ‘exposomes’.
The exposome is a measure of all the exposures of an individual from the moment of conception, including impacts from environmental and occupational sources, and how those exposures relate to health.
‘Using data from the Dubbo Osteoporosis Epidemiology Study, we have already identified more than 9000 linkages among diseases, and there were more links in osteoporosis compared with non-osteoporosis. For instance, we found that individuals with a fracture were more likely to have, among others, hypertension, osteoarthritis and diabetes.
‘Knowing the relationship between comorbidities, we will then go on to develop a predictive model that uses this ‘comorbidities network’ to determine a person’s risk of fracture. We expect that this project will provide an insight into the origins of osteoporosis and its related conditions.’ (From "Update in Osteoporosis Research", Sept 2017)