Title of project or programme

MRC Centre for Neuropsychiatric Genetics and Genomics

Principal Investigators of project/programme grant
Title Forname Surname Institution Country
Professor Michael Owen MRC Centre for Neuropsychiatric Genetics and Genomics UK
Address of institution of lead PI
Institution MRC Centre for Neuropsychiatric Genetics and Genomics
Street Address Cardiff University, Henry Wellcome Building, Heath Park
City Cardiff
Postcode CF14 4XN
Country
  • United Kingdom
Source of funding information

Medical Research Council

Total sum awarded (Euro)

3253685.72

Start date of award

03-08-2009

Total duration of award in months

60

The project/programme is most relevant to
  • Alzheimer’s disease and other dementias
  • Parkinson’s disease
  • Huntington’s disease
Keywords
Research abstract in English

The overarching mission of the proposed Centre will be to use genetics and genomics to inform our understanding of the aetiology, pathogenesis and classification of the major psychiatric and neurodegenerative disorders, and to train a cadre of clinical and non-clinical scientists capable of delivering the discovery and translational agenda.

Research will focus upon common psychiatric and neurodegenerative disorders. It will be organised around 5 major themes.

1. Psychosis and Major Affective Disorders- schizophrenia, bipolar and unipolar mood disorders;

2. Neurodegenerative Disorders- Alzheimer’s disease, Huntington’s disease, Progressive Supranuclear Palsy, Parkinson’s Disease;

3. Developmental Disorders- dyslexia, ADHD, childhood depression, pre-natal environmental influences on behaviour;

4. Genetic Mouse Models- genetics of impulsive behaviours, familial dementias (Alzheimer’s Disease, FTDP-17), sex chromosome effects on behaviour, genomic imprinting, behavioural epigenetics;

5. Biostatistics and Bioinformatics- this supports research in the above areas. This will be consolidated and developed, particularly in regard to bioinformatics, by institutional and MRC support if Centre status is awarded.

Our objectives over the next five years are to deploy the new opportunities afforded by technological advances and large sample sizes to identify new risk genes for psychiatric disorders and to explore the impact of specific genes across diagnostic boundaries and in relation to specific symptoms and dimensions. While much of the Centre’s work will remain focused on the identification of risk genes, we envisage an increasing emphasis on translational work over the next 5 years. The latter will be built upon a number of existing projects as well as several new strategic appointments and collaborations.

We request funding in order to: 1) enhance our training capability in particular by establishing a 4 year Centre PhD programme, 2) establish a new senior post in Bioinformatics at Lecturer/Senior Lecturer level in order to enhance our ability to compete in a very data rich environment, and to deliver the added value arising from our synergistic research programmes as well as to our training agenda, 3) establish an innovative public engagement and communications strategy in order to bring the results of our research closer to the patient and to application, 4) develop collaborations allowing us to explore the factors that mediate the effects of risk genes on clinical phenotypes in longitudinal, population-based cohorts.

Lay Summary

    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.

    Further information available at:

Types: Investments > €500k
Member States: United Kingdom
Diseases: Alzheimer's disease & other dementias, Huntington's disease, Parkinson's disease & PD-related disorders
Years: 2011
Database Categories: N/A
Database Tags: N/A

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