Principal Investigator: Dr Gerome Breen
Department: Institute of Psychiatry
Institution: King's College LondonTags: 16577, epidemiology, genetics, immune, Internalising, psychiatric
- Professor Andrew McIntosh
- Professor Bill Deakin
- Professor Daniel Smith
- Professor Michael O’Donovan
- Professor Peter Visscher
- University of Edinburgh, Division of Psychiatry, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh EH10 5HF.
- University of Manchester, Neuroscience and Psychiatry Unit, Stopford Building G907, Oxford Road, Manchester M13 9PT.
- University of Glasgow, Institute of Health and Wellbeing, Academic Centre Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow G12 0XH.
- Cardiff University, Institute of Psychological Medicine, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ.
- University of Queensland, Queensland Brain Institute, QBI Building, Upland Road, St Lucia, Queensland QLD 4072. Australia.
1a: Identify changes in DNA that increase the risk for psychiatric disorders alone (specifically the internalising disorders: depression, anxiety including OCD, and related disorders), and for these disorders in the presence of co-morbid physical disorders (autoimmune disorders, including rheumatoid arthritis, and non-immune disorders, including type 2 diabetes, migraine, chronic pain, obesity and body-mass index). Disorder status will be determined from the UK Biobank adjudicated health outcomes, including data from primary care , hospitals, and self-report. We will also explore whether the variants associated with each psychiatric disorder predict the likelihood that an individual has a given physical disorder.
1b: Understanding how genetics influence psychiatric disorders, and the relationship between psychiatric and physical disorders, will provide much-needed insight into the underlying biology. As well as increasing our understanding of interactions between the brain and body, this may identify target systems for the development of novel treatments in psychiatry; for example, the re-purposing of anti-inflammatory drugs for the treatment of schizophrenia and depression is a promising area of ongoing research. Furthermore, identification of shared genetic risk factors could assist in diagnosis by determining whether a given patient is high or low risk.
1c: Genotype information is being produced on the UK Biobank sample. We will use this to perform genome-wide association studies using publicly-available software packages, testing thousands of DNA variants for their association with different disorders. We will compare individuals with internalising disorders to controls, as well as comparing those with both a psychiatric and a physical disorder to those with only one (to identify genetic variants associated with having both disorders).
We will also explore the genetic overlap between a given psychiatric disorder and associated physical disorders, using the results from the association studies and publicly-available software packages.
1d: Full cohort
“We are seeking permission to ascertain the overlap between individuals in the UKBB and the PGC datasets. There is an established methodology for doing this, which has previously been applied successfully by our collaborators as part of project 4844 (STratifying Resilience and Depression Longitudinally (STRADL), PI: Professor Andrew McIntosh). We would use this data to exclude overlapping individuals and we would also return a flag to UK Biobank indicating an overlapping individual with the PGC’s current data freezes for depression, anxiety, bipolar disorder schizophrenia, and eating disorders.”