Examining the phenotypic expression of genetic risk for schizophrenia during development in a large, population-based, birth cohort study

Schizophrenia is a severe psychiatric disorder that imposes a substantial burden on sufferers, their families and society. With a peak incidence in early adulthood, it is one of the leading causes of disability worldwide. Sufferers have a high risk of suicide and increased mortality from other causes. Schizophrenia is characterised by psychotic experiences such as hallucinations and delusions, as well as by impairments in affect, cognition and social functioning.

Both genetic and environmental effects contribute to the aetiology of schizophrenia. Schizophrenia has a heritability of ≈80% and it is widely recognized that identifying genes conferring risk for this disorder, and studying their biological function, offers one of the best opportunities for increasing our limited understanding of the molecular and cellular processes underlying this disorder, and for the development of new and more effective treatments. Recent work from the largest schizophrenia consortium to date has identified over 100 genetic variants that show genome-wide statistical evidence of association with this disorder, with many thousands of variants across the genome showing weaker evidence of association. Whilst individual loci have small effects on risk, these genetic variants, en masse, explain approximately 20% of the variation in schizophrenia, and it is possible to derive a score based on this polygenic data to examine the association between increasing genetic risk for schizophrenia and other outcomes. For example it has been shown, using this approach, that bipolar disorder is associated with genetic risk for schizophrenia, whereas diabetes is not.

In this project the student will have the opportunity to examine how genetic risk for schizophrenia is expressed from childhood through early adulthood in a large population-based birth cohort, and examine the extent to which this risk is mediated through effects on psychopathology, neurocognitive function, or social behaviour during development.

This project will be supervised by Dr Stan Zammit & Prof Mick O’Donovan / Sir Prof Mike Owen