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Risk Factors Associated With The Expansion Of CGG Repeat Sequences In The FMR1 (fragile X) Gene: A Study In Tasmania
Funder
National Health and Medical Research Council
Funding Amount
$246,020.00
Summary
This study will identify the risk factors that lie in an individual's DNA profile for a disease called fragile X syndrome. This disease is the most common form of intellectual disability that runs in families caused by an unusual form of change in a particular gene called FMR1, whereby a very short sequence of DNA in a gene expands by repeating itself to such an extent that once it reaches a certain size the whole gene stops working and the disease occurs. The expansion in the gene is not unifor ....This study will identify the risk factors that lie in an individual's DNA profile for a disease called fragile X syndrome. This disease is the most common form of intellectual disability that runs in families caused by an unusual form of change in a particular gene called FMR1, whereby a very short sequence of DNA in a gene expands by repeating itself to such an extent that once it reaches a certain size the whole gene stops working and the disease occurs. The expansion in the gene is not uniform across the generations, and only occurs when passed on from the mother to her offspring. However, many females carrying only a short sequence may pass on, for unknown reasons, either a large expanded sequence leading to disease, or one similar in size to her own. This complexity in the progression of the number of CGG repeats means that there is a relatively large number of mothers, ~1 in 300, who are quite normal but at risk of having an affected offspring. The factors that trigger this expansion in the DNA are presently not well understood, but a number of genetic markers in the FMR1 gene have been implicated. This study will assess the contribution of an array of these genetic markers in determining the risk of expansion of the short repeat from mother to offspring and hence the risk of fragile X. Conducting this study in Tasmania has two advantages. First, by having access to genealogical records that permit the linking of fragile X families we shall be able to identify common predisposing factors of fragile X more accurately. Second, by testing the whole population with intellectual disability in one State of manageable size we shall obtain an unbiased estimate of the prevalence of fragile X.Read moreRead less
The Beyondblue Schools Research Initiative: A Two-year Follow-up.
Funder
National Health and Medical Research Council
Funding Amount
$827,285.00
Summary
The prevalence of Depressive Disorders among children and adolescents was estimated in the Australian National Child and Adolescent Mental Health Survey to be 3.7%. This means that at any single point of time, approximately 138,000 Australian children and adolescents are experiencing a Depressive Disorder. Furthermore, the National Survey found that less than half (46%) of those with a Depressive Disorder received any help over a 6 month period prior to the survey, with only 8% attending a menta ....The prevalence of Depressive Disorders among children and adolescents was estimated in the Australian National Child and Adolescent Mental Health Survey to be 3.7%. This means that at any single point of time, approximately 138,000 Australian children and adolescents are experiencing a Depressive Disorder. Furthermore, the National Survey found that less than half (46%) of those with a Depressive Disorder received any help over a 6 month period prior to the survey, with only 8% attending a mental health clinic, and only 4% attending a hospital-based Department of Psychiatry. These findings emphasise the importance of finding alternative approaches to help the large number of young people with depression who do not receive help from professional services. This application seeks funding to evaluate the beyondblue Schools Research Initiative. The key features of the initiative are the development of a strong partnership between the health and education sectors and a focus on both individual-level and school-level risk factors. This has enabled us to provide a much longer duration of intervention than previous studies, to test the intervention in several different Australian States, and to utilise a broadly based intervention that includes a range of approaches, each of which have the potential to help reduce adolescent depression. The significance of the project lies in its potential to identify effective interventions which can reduce rates of depression experienced by adolescents, and the quality of the ongoing research partnership we have established across the education and health sectors. We anticipate that this partnership will be utilised for ongoing research in this area.Read moreRead less
Osteoporosis is a major and increasing public health problem. Fracture, the ultimate consequence of osteoporosis is associated with significant morbidity, mortality and economic costs. The Dubbo Osteoporosis Epidemiology Study, starting in 1989, with over 2000 women and men, is one of the longest running epidemiological studies in osteoporosis worldwide. It has been at the forefront of epidemiological advances in osteoporosis. It has identified osteoporotic fracture risks including low bone dens ....Osteoporosis is a major and increasing public health problem. Fracture, the ultimate consequence of osteoporosis is associated with significant morbidity, mortality and economic costs. The Dubbo Osteoporosis Epidemiology Study, starting in 1989, with over 2000 women and men, is one of the longest running epidemiological studies in osteoporosis worldwide. It has been at the forefront of epidemiological advances in osteoporosis. It has identified osteoporotic fracture risks including low bone density and bone loss, muscle weakness and postural instability, as well as the extent of the problem in men, and the significant costs, ill-heath and mortality associated with fracture. Despite the clarification of risk factors over the past decade, there are significant gaps in knowledge about osteoporosis, particularly in the accurate prediction of fracture risk and in identification of factors related to fracture-associated mortality and survival post fracture. Although bone density is one of the best predictors of fracture risk, it incompletely discriminates between those who will fracture from those who will not. Although a number of clinical risk factors, and other measures of bone strength, such as quantitative ultrasound and geometry, have been shown to be independent predictors of fracture risk, it is not clear that these measures can be integrated with BMD to improve fracture prediction. The aim of the current study, is to develop and validate models using bone density, other measures of bone strength and clinical parameters that will more accurately predict fracture risk and mortality following fracture in older men and women. The more precise identification of those at high risk of fracture and at risk for poor outcomes following fracture will provide a rational basis for the development of more cost effective interventions for prevention of fracture and its associated morbidity and mortality.Read moreRead less
Risk Factors For The Development Of Eating Disorder Phenotypes And Endophenotypes In Adolescent Twins
Funder
National Health and Medical Research Council
Funding Amount
$266,500.00
Summary
The overall aim of the project is to develop a better understanding of how environment, temperament and genes work together to cause disordered eating and eating disorders. Eating disorders, including anorexia nervosa and bulimia nervosa, are an extremely difficult and costly condition to treat, and are associated with high mortality. Eating disorders in adolescence lead to increased risk for anxiety disorders, chronic fatigue, chronic pain, depressive disorders, infectious diseases, suicide att ....The overall aim of the project is to develop a better understanding of how environment, temperament and genes work together to cause disordered eating and eating disorders. Eating disorders, including anorexia nervosa and bulimia nervosa, are an extremely difficult and costly condition to treat, and are associated with high mortality. Eating disorders in adolescence lead to increased risk for anxiety disorders, chronic fatigue, chronic pain, depressive disorders, infectious diseases, suicide attempts, and limitation in activities due to poor health in adulthood. Full- and partial-syndrome eating disorders affect around 10% of adolescent girls. Given the seriousness of the consequences of eating disorders, and the large number of Australians affected, a better understanding of what causes the development of eating disorders is required. The current research investigates identical and non-identical adolescent female twins aged 13-15 years. As well as examining their eating, this study will look at the sort of environments and temperaments that may increase genetic susceptibility to develop eating problems. The types of environment to be examined include media influence, weight related peer teasing, parental dieting, and pre- and pernatal complications. Twin temperament will also be examined, including perfectionism, sense of ineffectiveness, body dissatisfaction and depression. Parental anxiety and novelty seeking will also be examined for impact on the development of disordered eating in their children. The twins will be followed up over a 2-year period, the peak risk age for onset of eating problems. By comparing the identical and non-identical twins, we can define the characteristics of those most at risk of developing eating problems. The results of this project can be used to formulate specific prevention strategies.Read moreRead less
Depression And Risk Of Coronary Heart Disease: A Prospective Study Of Mediating Haemostatic Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$327,625.00
Summary
Growing evidence suggests that depression, anger and anxiety play a role in causing coronary heart disease (CHD) and complicating the outcome in existing CHD. This may occur by effects of these emotions on promoting blood clotting and the stickiness of platelets - the blood cells responsible for blood clotting. This pilot study will follow a group of people with depression but without CHD and a control group over 8 months to compare how the blood clotting profile changes as depression resolves. ....Growing evidence suggests that depression, anger and anxiety play a role in causing coronary heart disease (CHD) and complicating the outcome in existing CHD. This may occur by effects of these emotions on promoting blood clotting and the stickiness of platelets - the blood cells responsible for blood clotting. This pilot study will follow a group of people with depression but without CHD and a control group over 8 months to compare how the blood clotting profile changes as depression resolves. The potential benefits of this research are a better understanding of the links between the common illnesses of depression and CHD that might improve the prevention and treatment of heart disease.Read moreRead less
Is NADPH Oxidase The Trigger For Accelerated Atherosclerosis Caused By Bacteria?
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
Cardiovascular disease is the leading cause of death and morbidity world-wide. However, its incidence is not fully explained by the presence of conventional risk factors, such as high cholesterol, hypertension, diabetes and cigarette smoking. Steadily growing evidence indicates that bacterial infection, particularly by Chlamydia pneumoniae and Helicobacter pylori, is also strongly linked to atherosclerotic lesion formation and increased risk of a cardiovascular event. This project will investiga ....Cardiovascular disease is the leading cause of death and morbidity world-wide. However, its incidence is not fully explained by the presence of conventional risk factors, such as high cholesterol, hypertension, diabetes and cigarette smoking. Steadily growing evidence indicates that bacterial infection, particularly by Chlamydia pneumoniae and Helicobacter pylori, is also strongly linked to atherosclerotic lesion formation and increased risk of a cardiovascular event. This project will investigate a new aspect to the body s defence against bacterial infection which involves production of oxygen radicals by the blood vessel wall. We propose that although this response of the artery to bacteria in the blood is beneficial in the short term, it inadverently initiates a chronic inflammatory process that ultimately accelerates development of artery disease. If this is the case, the oxygen radical production by the enzyme, NADPH oxidase, in the artery wall may represent the missing link between bacterial infection and atherosclerosis. We will therefore firstly test whether two bacteria, Chlamydia pneumoniae and Helicobacter pylori, can acutely induce artery inflammation in this way. We will then perform definitive studies to test whether mice infected with these bacteria develop accelerated atherosclerosis, and if so, whether this effect is dependent on NADPH oxidase activity in the artery wall. Finally, we will test the efficacy and importance of timing of antibiotic therapy to prevent atherosclerotic lesion formation.Read moreRead less
Increasing Cardiovascular Risk Assessment In First Degree Relatives Of Patients With Premature Heart Disease: An RCT
Funder
National Health and Medical Research Council
Funding Amount
$113,972.00
Summary
Family history is a risk factor for ischaemic heart disease (IHD), especially if the history includes early onset disease. Families share both genetic and environmental risk factors, many of which can be modified to reduce the risk of heart disease. The aim of this project is to trial an intervention to promote heart disese risk assessment among the relatives of patients with premature heart disease. This is a first step toward prevention of heart disease in these families.
Measurement And Prognostic Significance Of Retinal Vessel Parameters In Childhood
Funder
National Health and Medical Research Council
Funding Amount
$264,175.00
Summary
We propose that structural micro-vessel changes associated with blood pressure develop early in childhood and that these may predict future cardiovascular risk in adulthood. In order to address this important issue, we will measure retinal vascular diameter and other microvascular signs from retinal photographs taken of a large population-based sample of Sydney schoolchildren (n-4,093) during 2003-2005. This project included 1740 6-year olds and 2353 12-year olds from 52 schools across Sydney. A ....We propose that structural micro-vessel changes associated with blood pressure develop early in childhood and that these may predict future cardiovascular risk in adulthood. In order to address this important issue, we will measure retinal vascular diameter and other microvascular signs from retinal photographs taken of a large population-based sample of Sydney schoolchildren (n-4,093) during 2003-2005. This project included 1740 6-year olds and 2353 12-year olds from 52 schools across Sydney. Almost all had photos taken. We will test the hypothesis that retinal arteriolar calibre in children is strongly influenced by ambient (current) blood pressure, after accounting for confounding influences of image magnification (eye shape , size and refraction) and size of the child (body mass). We also predict that familial, eye and general health factors also determe diameter of retinal vessels, and will account for these in the analysis. We will test the notion that certain retinal vessel branches or trunks will be more affected by blood pressure variability than others. This finding, if shown, could improve our understanding of retinal micro-vessel signs in older adult populations and may assist developments of rapid image scanning to assess vessel diameter. In a pilot study grading retinal vessel diameters from one eye of a random sample of the 6-year old images, we found that increasing blood pressure was strongly associated with slightly narrower retinal arterioles. Though modest in magnitude, this effect was highly significant and was independent of other factors found to determine retinal vessel diameter. Evidence is emerging that cardiovascular disease may be linked to BP levels in early life. It seems possible that retinal micro-vessel changes in children may also predict future cardiovascular risk in adulthood. This research will evaluate measures to study the long-term effects of variations in blood pressure and its genesis in childhood.Read moreRead less