The Phenotypic Expression of Neuropsychiatric Copy Number Variants (360G-Wellcome-201171_Z_16_Z)

Copy number variants (CNVs) are associated with neuropsychiatric disorders across diagnostic boundaries. The phenotypes associated with most neuropsychiatric CNVs are poorly defined. The aims of this project are to identify CNV carriers and establish the psychiatric, cognitive and neurodevelopmental phenotypes associated with neuropsychiatric CNVs. Two approaches will be used: (i) examining neurocognitive phenotypes of CNV carriers in the largest available population sample (Biobank UK), (ii) recalling CNV-carrying individuals from psychiatric genetic datasets and characterising their psychiatric, cognitive and neurodevelopmental phenotypes. I hypothesise that CNV-carrying individuals will display more frequent and severe impairments than those without CNVs. The first stage of the project will involve calling CNVs in 500,000 individuals (Biobank UK). I will analyse these data for associations between individual CNV loci and phenotypic domains tapping mental health, cognitive functioning and neurodevelopment. In the second stage, I will develop expertise in deep phenotyping by recalling and investigating individuals with psychiatric disorders and CNVs and comparing to those with equivalent psychiatric disorders without CNVs. Participants will undergo comprehensive assessment including psychiatric (SCAN) interview, Autism Quotient questionnaire, CANTAB Schizophrenia Cognitive Battery, developmental history, examination for soft neurological signs (Neurological Evaluation Scale) and dysmorphology assessment with clinical photography (adapted Waldrop Scale).