The phenotypic expression of neuropsychiatric copy number variants

Large, rare copy number variants (CNVs) are associated with neurodevelopmental disorders but there is limited evidence on their phenotypic effects in individuals who do not develop these phenotypes. The aim of this thesis was to establish the effects of 53 neurodevelopmental disorder associated CNVs on individuals with and without psychiatric disorders, in psychiatric, cognitive and physical health domains. In analyses of individuals without neurodevelopmental disorders in UK Biobank, carriers of 53 neurodevelopmental CNVs performed more poorly than CNV noncarriers across seven cognitive tasks and related functional outcome measures. In the same group of individuals, neurodevelopmental CNVs were associated with an increased risk of depression. I assessed 5 carriers of neurodevelopmental CNVs and 22 CNV noncarriers with psychiatric disorders from the Cardiff Cognition in Schizophrenia Study (Cardiff COGS) and National Centre for Mental Health (NCMH) cohorts. I also analysed previously collected data from 76 CNV carriers and 2,389 CNV noncarriers from NCMH. CNV carriers tended to have primary diagnoses and family histories from the neurodevelopmental spectrum, and had a greater number of both psychiatric and physical health diagnoses than CNV noncarriers. CNV carriers also displayed greater deficits in assessments of negative symptoms and tended to be more likely to report delays in walking and talking. The findings of this PhD add to the evidence on the phenotypic spectrum of neurodevelopmental CNVs, generate hypotheses for future work investigating the role of CNVs in psychiatric disorders and provide a starting point for the translation of these findings to the clinic