Overview of MRC Centre for Neuropsychiatric Genetics and Genomics

1. Overview of MRC Centre for Neuropsychiatric Genetics and Genomics Michael J Owen

2. Mission Use genetics and genomics to inform our understanding of the aetiology, pathogenesis and classification of the major psychiatric and neurodegenerative disorders. Train a cadre of clinical and non-clinical scientists capable of delivering this discovery and translational agenda. Clinical Studies Genetics Pre-clinical Studies Population Studies

3. Major disease foci The major causes of psychiatric morbidity and mortality including: Neurodegenerative disorders Alzheimer disease Parkinson disease Huntington disease Schizophrenia Mood disorder Bipolar Disorder Unipolar Disorder Childhood psychiatric and developmental disorders ADHD Depression Dyslexia

4. Cross cutting themes • Psychosis and Major Affective Disorders. • Nick Craddock • Neurodegenerative Disorders. • Julie Williams • Developmental Disorders. • Anita Thapar • Genetic and Cellular models. • Lawrence Wilkinson • Biostatistics and Bioinformatics. • Peter Holmans

5. 2010 Cardiff University establishes 3 cross school research institutes.

6. NMHRI Mission Harness the internationally recognised strengths in neuroscience research in Cardiff to deliver new insights into the major neurodegenerative and psychiatric disorders. Major focus on developing novel translational interfaces between the work of MRC Centre for Neuropsychiatric Genetics and Genomics and the wider Cardiff Neurosciences community.

7. The Gateway Building

8. MRC centre support for biostatistics and bioinformatics • Databasing and biostatistics posts. • SL in bioinformatics/ computational biology. • 3 joint PhD students with COMSC. • Regular forum • to encourage joint research. • Existing collaboration on MSc.

9. Genomic data Genome-wide association studies Genome-wide copy number variation Whole exome and genome sequencing Other data Transcriptomics Proteomics Annotated complexes and pathways Brain imaging Cognition Clinical including routinely collected data Very complex genetics We seek insights into: Association of single and multiple DNA events with other datasets Nature of interactions Disease pathways and other biological relationships What we do

11. BD: modulation of transcription and cellular activity, including via hormonal action

12. Copy Number Variants deletion Comparative Genomic Hybridisation duplication SNP Chips 12

13. Do SZ CNVs converge on synaptic pathways? • Causal role of most individual CNVs not established • Annotation gap • Biases esp gene size not excluded in most studies • One study using formal test found nominal evidence for enrichment in “neuronal-activity” and “learning gene” sets in ISC vs controls (Raychaudhuri et al 2010). • Study of de novos

14. Challenges • Extracting biological meaning from multiple genetic signals • Algorithms and platforms for estimating disease risk • Prediction of functional consequences of sequence variation • Understanding relationships between complex genomic data and complex phenotype data (clinical, cognitive, imaging etc) • Linking research and routinely collected clinical data