A Genome-wide Linkage Study Of Schizophrenia In A Large Sample From Tamil Nadu, India
Funder
National Health and Medical Research Council
Funding Amount
$500,000.00
Summary
A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling familie ....A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. We have been recruiting families with at least two siblings with schizophrenia from a number of communities-casts in Tamil Nadu. We plan to recruit a total of 400 affected sibling families, together with 400 trio families (both parents, plus their affected child). A genome-wide scan of the genetic code in all individuals will be conducted to identify chromosomal regions linked to schizophrenia. This is the first necessary step toward identifying schizophrenia susceptibility genes. If one or more genes are discovered, this will greatly improve our understanding of this disease. It will also stimulate the search for similar genes in other samples world-wide, including Australia where schizophrenia costs $2.5 billion annually in terms of treatment and loss of employment. With such a discovery, it may be possible to find better treatments that correct the basic cause of the illness and identify factors that protect against the illness.Read moreRead less
A Genetic Study Of Schizophrenia In The Brahmin Of Tamil Nadu
Funder
National Health and Medical Research Council
Funding Amount
$267,226.00
Summary
The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how it is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. Societies such as Australia are genetically diverse because people from many different ethnic groups have intermarried. To detect susceptibility genes in this type of population, we must study very large patient samples. Alternatively, we can ....The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully understand how it is inherited, but it is very complex, and several interacting genes as well as environmental factors are probably involved. Societies such as Australia are genetically diverse because people from many different ethnic groups have intermarried. To detect susceptibility genes in this type of population, we must study very large patient samples. Alternatively, we can study genetically homogenous patient samples, found in isolated gene-pool populations. One such population is the Brahmin people in Tamil Nadu, a south-eastern state of India. The Brahmin are descended from the Aryan peoples who migrated into southern India 2000 years ago. In the Hindu caste system, Brahmin are the highly educated priest class, and enjoy a privileged position in society. Traditionally, marriages among the Brahmin of Tamil Nadu have been prearranged, with a preference for first-cousin marriages. As well as this cultural and historical evidence, genetic marker studies confirm that this population is a suitable genetic isolate. In this project, genetic material (DNA) will be collected from Brahmin schizophrenic patients and their families. Diagnostic data, detailed family data, and blood samples will be gathered from 90-100 extended families, each containing two or more ill individuals. Analysis of their genetic code will enable a search for possible schizophrenia susceptibility genes and a systematic search for a mutation. If found, this will greatly improve our understanding of schizophrenia, and stimulate the search for similar genes in other samples world-wide, including Australia where schizophrenia costs $3 billion annually in terms of treatment and lost jobs. If schizophrenia genes can be found, it may be possible to find better treatments that correct the basic causes of the illness and identify factors that protect against the illness.Read moreRead less
Identifying EQTLs And Endophenotyping Known CNVs In A Large Australian Schizophrenia Sample
Funder
National Health and Medical Research Council
Funding Amount
$902,472.00
Summary
This study hopes to identify genetic code variations associated with an increased risk of schizophrenia . We will study variation in gene expression levels in patients and healthy controls to identify underlying changes in the genetic code responsible. In a subset of patients with schizophrenia and known rare copy number variations (CNVs) in the genetic code we will conduct brain scans and psychological tests to characterize the effect of CNVs on brain structure and function in schizophrenia.
Schizophrenia affects 1 in 100 people, and yet its causes remain largely unclear. To improve understanding, treatment and management of the disease, the team performing this research will evaluate whether mobile DNA elements found in our genome are activated by stress and thereby alter how brain cells work in individuals affected by schizophrenia. They will also test whether mobile DNA can be blocked by drugs, perhaps revealing new strategies to treat the disease.
Identification Of Schizophrenia Susceptibility Genes: A Collaborative Project With The University Of Indonesia
Funder
National Health and Medical Research Council
Funding Amount
$546,825.00
Summary
Schizophrenia is present in all populations at a similar incidence. The project aims to identify genetic risk factors in three genomic regions previously detected by us in a genome-scan for genetic linkage in 152 Indonesian families. Colleagues at the University of Indonesia will collect an additional sample of 2000 individuals for replication. This sample will be available for research in Australia. Knowledge of risk factors will aid in diagnosis, prevention, and development of novel therapies.
Neuregulin Dependent Neuronal Migration And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$297,128.00
Summary
Schizophrenia effects 1-100 Australians and is responsible for $2.2 billion in health costs, disables thought and emotion and is devastating to the individual, the family and the community. We need to develop drugs able to reverse the root cause of schizophrenia. We know that schizophrenia is caused by risk genes and environments and impacts brain maturation. We will test how one such gene, neuregulin, acts to derail the normal development of the human cerebral cortex in patients who suffer.
Muscarinic M1 Receptor, Cognition And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$598,800.00
Summary
Schizophrenia is a serious psychiatric illness that affects approximately 1% of Australia's population. Whilst the prominent symptom of schizophrenia is psychosis, the majority of subjects with schizophrenia also show deficits in cognition. Unlike psychotic symptoms, deficits in cognition do not respond well to current antipsychotic drug treatment. We have been investigating the possible role for changes in a family of receptors, called muscarinic receptors, in the pathology of schizophrenia for ....Schizophrenia is a serious psychiatric illness that affects approximately 1% of Australia's population. Whilst the prominent symptom of schizophrenia is psychosis, the majority of subjects with schizophrenia also show deficits in cognition. Unlike psychotic symptoms, deficits in cognition do not respond well to current antipsychotic drug treatment. We have been investigating the possible role for changes in a family of receptors, called muscarinic receptors, in the pathology of schizophrenia for almost a decade. Our research has shown that two members of the muscarinic receptor family, the M1 and M4 receptors, may be differentially decreased in different brain regions of subjects with schizophrenia. Recently, we have shown that in the dorsolateral prefrontal cortex, the muscarinic receptor that is decreased in schizophrenia is the M1 receptor. Since we made this discovery another group has shown that a mutation in the M1 receptor may be a cause of cognitive deficits in schizophrenia. We are now proposing a study using parallel streams of research on postmortem brain tissue and in living subjects with schizophrenia to determine the likelihood that decreases in M1 receptors in the cortex may be the cause of cognitive deficits in schizophrenia. This will involve confirming that mutations in the M1 receptor, measured using DNA from white blood cells, are associated with cognitive deficits in schizophrenia. At the same time we will determine if the same mutation is associated with low levels of M1 receptors in cortex obtained postmortem from subjects with schizophrenia. If both these are true this will give us a strong platform to suggest that low levels of cortical M1 receptors are associated with cognitive deficits in schizophrenia.Read moreRead less
Multivariate Whole Genome Estimation And Prediction Analysis Of Genomics Data Applied To Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$639,582.00
Summary
We have made major contributions to the development of statistical methods applied to data from the international Psychiatric Genomics Consortium. Major new data sets will soon become available, with immense sample sizes (100,000s) and more extensive clinical and environmental data. We will develop and apply novel statistical analyses of these data, to answer fundamental questions about the genetic basis of psychiatric disorders and the interplay of genetic and environmental risk factors.