Principal Investigators


Professor Sir MJ Owen

Institution


Cardiff University

Contact information of lead PI


Country


United Kingdom

Title of project or programme


MRC Centre for Neuropsychiatric Genetics and Genomics

Source of funding information


MRC

Total sum awarded (Euro)


€ 2,395,297

Start date of award


25/11/2014

Total duration of award in years


5.0

The project/programme is most relevant to:


Alzheimer's disease and other dementias | Parkinson's disease and PD-related disorders | Neurodegenerative disease in general

Keywords


ADHD| Alzheimer Disease| Bipolar Disorder| Genetics| Neurology| Neuroscience| Parkinson Disease| Psychiatry| Psychosis| Schizophrenia

Research Abstract


We have established a Centre of Excellence in psychiatric genetics, focusing on psychiatric and neurodegenerative disorders such as schizophrenia, bipolar disorder, depression, ADHD, Alzheimer disease and Parkinson disease. Over the next 5 years we will retain a strong focus on gene discovery in order to deliver further important insights into disease pathogenesis. We will do this though our clinical, genetic and statistical expertise, our access to suitable patient cohorts, and our proven ability to participate in and provide leadership in large consortia. We will also continue to benefit from our structure of overlapping disease themes supported by a strong genomics, statistical and bioinformatics core. There will be an increasing focus on identifying rare mutations by NGS, and on understanding the significance of genetic findings for risk mechanisms, which will require integration with data from a variety of sources. Moreover, we are now well placed to use genetic findings to obtain greater understanding of pathogenic mechanisms, improve classification, identify biomarkers to aid prediction and intervention and identify novel treatment targets. Broadly speaking this work will take place in two settings. First we will explore the factors that mediate the effects of risk alleles on clinical phenotypes in longitudinal, population-based cohorts and identify biomarkers and modifiable markers of risk through integration of data from other risk factors, gene expression and epigenomics. Second, we will study the impact of risk alleles at molecular, cellular and systems levels through our imaging and cellular/animal models themes. Work in these areas will benefit from our access to patients carrying specific rare, high-penetrance mutations and has been greatly strengthened by our central participation in the Cardiff University Neuroscience and Mental Health Research Institute with which we will be co-located in the new Hadyn Ellis building.

Lay Summary


The main goal of the Centre is to understand how genes are involved in a range of common psychiatric and neurological disorders, and to use this knowledge to improve our understanding of how these diseases arise and to develop new approaches to diagnosis and treatment. We have known for a long time that genes play an important role in disorders such as schizophrenia, bipolar disorder, depression, attention deficit hyperactivity disorder (ADHD), Alzheimer disease and Parkinson disease. Now, using modern genetic technologies, we have begun to identify some of the specific genes involved. Centre scientists have been at the heart of these exciting developments, which have begun to yield novel insights into the brain mechanisms involved, and which have also raised important questions about the validity of current diagnostic approaches. For example our work has shown that intellectual disability, autism, ADHD and schizophrenia are likely to be much more closely related than previously believed. Our success with existing methods, together with the development of new approaches particularly the ability to determine the sequence of DNA (the genetic code) in large numbers of patients, means that we are confident that further work will allow us to identify more of the genes involved in these disorders and that this will deliver greater understanding into how these diseases arise and the relationships between them. Thus a major focus of ours over the next 5 years will be to continue our work aimed at identifying disease genes in these disorders and in understanding how genetic risk operates both across and within current diagnostic categories. The second major focus of our work will be look at how risk genes lead to illness. This will be essential if we are to understand the mechanisms by which these diseases come about. This work will use a variety of approaches. First, we will look at the impact of risk genes in the general population for example on indexes of brain and cognitive development in the case of psychiatric disorders and on markers of inflammation, and cardiovascular health in the case of Alzheimer disease. This will help us understand how disease develops across the lifespan, and identify potentially modifiable risk factors or makers of those at increased risk of subsequent disease. The latter will be important for future studies aimed at early intervention. Second, we will develop animal and cellular models allowing us to study in detail the impact of risk genes on the function of nerve cells and brain circuits and on behaviour. Finally, we will study in human volunteers and patients how risk genes impact on brain structure and function using brain imaging methods. By studying cells, animals and patients we will be able to link abnormalities in brain function and behaviour seen in patients to abnormalities in cells and brain circuits. This will help us develop methods to stratify patient populations into specific groups for treatment studies as well to understand the mechanisms by which these diseases develop. These advances will be essential if we are to develop novel and more effective treatments for these disabling conditions.

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