Molecular & Neuropsychological Predictive Markers Of Cognitive Decline.
Funder
National Health and Medical Research Council
Funding Amount
$429,500.00
Summary
Alzheimer's disease (AD) is a major cause of dementia in the elderly. As populations worldwide are living longer the prevalence of AD is predicted to rise markedly and in addition to the huge emotional burden on families the economic implications to the community at large is severe. Thus our aging veteran population and their spouses are particularly vulnerable to this devastating disease. Recent developments in AD research have resulted in a number of therapeutic strategies being undertaken wit ....Alzheimer's disease (AD) is a major cause of dementia in the elderly. As populations worldwide are living longer the prevalence of AD is predicted to rise markedly and in addition to the huge emotional burden on families the economic implications to the community at large is severe. Thus our aging veteran population and their spouses are particularly vulnerable to this devastating disease. Recent developments in AD research have resulted in a number of therapeutic strategies being undertaken with several of these now in phase 2 clinical trials. However for these treatments to be most effective early diagnosis is crucial. Currently, definite diagnosis is restricted to post-mortem examination of the brain for the presence of characteristic neuropathological features. This project proposes to identify individuals at high risk of developing cognitive decline leading to AD by using a battery of biochemical, genetic and neuropsychological markers. This study builds on our earlier work which followed a cohort of memory complainers and demonstrated that subjects in this group have lower cognitive scores and an increased frequency of the genetic risk factor, the e4 allele of apolipoprotein E. Follow up of this well studied cohort with more sensitive and extensive neuropsychological tests together with other genetic and biochemical markers will be important in identifying those risk factors that have positive predictive value for cognitive decline thereby contributing towards enhancing the therapeutic efficacy of current symptomatic and future drugs directed at the cause of AD.Read moreRead less
Accurate Prediction Of Individual Risk To Disease From Genome-wide Association Studies
Funder
National Health and Medical Research Council
Funding Amount
$269,371.00
Summary
Risk for many complex diseases (such as psychiatric disorders or heart disease) has a substantial genetic component, however few specific high risk variants have been identified. Evidence is mounting that there are likely to be hundreds of risk loci each individually conferring a very low increase in relative risk for disease. We aim to develop methods that utilise information from multiple genetic risk variants simultaneously to create a 'genomic profile' of risk.
New Computational Methods For The Analysis Of Whole-genome Data
Funder
National Health and Medical Research Council
Funding Amount
$151,516.00
Summary
A complete understanding of the mechanisms underlying common diseases can only be achieved if all pathways at which genetic variation contributes to disease risk are identified. Most available methods to identify such predisposing genetic variation are adequately powered only when analysing data for many thousands of samples. We will develop more powerful statistical methods that can increase our ability to identify disease genes from large-scale association studies.
Finding The Genetic Causes Of Asthma: The Australian Asthma Genetics Consortium (AAGC)
Funder
National Health and Medical Research Council
Funding Amount
$1,697,639.00
Summary
Asthma is a major burden on individuals and health systems. Despite many decades of research, no major effective new treatments for asthma have emerged recently. We will establish a large international consortium to systematically test nearly all known human genes to identify those that influence asthma susceptibility. We expect to identify pathways not previously implicated in asthma and so lead to a potential breakthrough in the development of more effective treatments.
Major Histocompatibility Complex (MHC) Genetics Of Ankylosing Spondylitis
Funder
National Health and Medical Research Council
Funding Amount
$568,612.00
Summary
Ankylosing spondylitis (AS) is the prototypic condition of a group of types of inflammatory arthritis called 'seronegative spondyloarthropathies'. These conditions are the most common form of inflammatory arthritis in white populations and occur worldwide. One third of the risk of developing AS is determined by genes within a region called the 'major histocompatibility complex' (MHC), in addition to the gene HLA-B27, the main gene causing AS. We aim to identify the remaining MHC genes.
The Immunogenetics Of Ankylosing Spondylitis: A Genetic And Functional Investigation Of IL23R And Related Genes
Funder
National Health and Medical Research Council
Funding Amount
$536,679.00
Summary
Ankylosing spondylitis (AS) is a common inflammatory arthritis which causes primarily back pain and stiffness, and affects 1-250 individuals. Our group identified association between tagging genetic markers in the gene IL23R and AS, and our preliminary data suggests some related genes are involved as well. This study aims to identify the key genetic variants involved and determine the mechanism by which they cause AS.
Australian Stroke Genetics Collaborative - Genome-wide Association Study In Ischaemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$1,141,037.00
Summary
The majority of stroke is caused by atherothrombosis, the formation of blood clots in brain blood vessels. Numerous genes are linked to atherothrombosis, but many studies examined genetic influences in isolation from environmental risk factors. We will examine the relevance of genetic variations linked to atherothrombosis, in the context of environmental risk factors. By determining the contribution of genetic and environmental factors in stroke, we will develop a stroke risk assessment tool.
The Role Of Collagenase (MMP-1) In The Pathogenesis Of Human Pterygia
Funder
National Health and Medical Research Council
Funding Amount
$246,100.00
Summary
Pterygia are a common, recurrent, disfiguring, and sight-threatening disease of the human eye. This disease is extremely common world wide and particularly in the Australian aboriginal population. The triggers for this disease are unknown. Prolonged exposure to environmental elements, such as ultra violet (UV) light, is proposed to be the main initiating factor. Our previous studies have shown the important role played by a family of proteolytic enzymes (metalloproteinases) in the progressive an ....Pterygia are a common, recurrent, disfiguring, and sight-threatening disease of the human eye. This disease is extremely common world wide and particularly in the Australian aboriginal population. The triggers for this disease are unknown. Prolonged exposure to environmental elements, such as ultra violet (UV) light, is proposed to be the main initiating factor. Our previous studies have shown the important role played by a family of proteolytic enzymes (metalloproteinases) in the progressive and invasive nature of pterygia. We have significant preliminary evidence that a large percentage of patients with pterygia carry a mutation in one of these enzymes (collagenase-1). This is the most abundant enzyme expressed in pterygium tissue and probably plays a major role in invasion and progression in this disease. UV light activates cells in pterygia to induce expression of collagenase-1. This study will determine whether or not people with a genetic predisposition are more likely to develop pterygia and whether or not environmental factors, such as UV light, trigger progression of disease. If this is the case, then subjects with this genetic predisposition would be at increased risk for the development of pterygia (and their complications) and could be advised to take preventative measures to minimize the risk of developing this disease.Read moreRead less
Environmental Risk Factors For Iron Overload-related Disease In A Cohort Study Of Hereditary Haemochromatosis
Funder
National Health and Medical Research Council
Funding Amount
$152,936.00
Summary
Results published last year from our Melbourne HealthIron study of hereditary haemochromatosis (iron overload disease) show that almost one third of the 50,000 men genetically at risk of iron overload in Australia will develop symptoms of disease including fatigue, arthritis and liver damage. We will use data from the recent follow-up of the Health2020 cohort, of which HealthIron is a sub-study, to determine environmental risk factors for progression to disease in people with iron overload.
Early Versus Delayed Therapeutic Venesection For The Prevention Of Hereditary Haemochromatosis
Funder
National Health and Medical Research Council
Funding Amount
$196,012.00
Summary
This study will investigate treatment by blood removal for the inherited iron overload condition hereditary haemochromatosis: Is treatment more effective in reducing risk of disease if performed early as a preventive measure rather than later after diagnosis with symptoms? Details of the lifetime history of blood donation from the Australian Red Cross Blood Service will be combined with existing information from questionnaires and clinical examination of 1,439 study participants in Melbourne.