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• W1525782170 abstract "Schizophrenia is a highly heritable, common psychiatric disorder. Although onset generally occurs during adolescence, multiple lines of evidence point to a neurodevelopmental insult that occurs many years prior to the presentation of symptoms. Many different approaches have been used to elucidate the genetic risk factors and their impact; however, few unequivocal facts have been established. With a considerable amount of data publically available, integrative approaches look to leverage multiple data sources to identify coherent themes. This thesis investigates the neurodevelopmental hypothesis of schizophrenia by incorporating results from genome-wide association studies and copy number variation studies with gene expression datasets, with the overall aim of identifying functional pathways that may be disrupted in the aetiology of the disorder.This study used foetal and developmental expression datasets of the human brain and statistical approaches to characterise the expression profiles of schizophrenia risk genes. Both spatial profiles in the mid-foetal brain and temporal profiles across development were considered. Data from genome-wide association studies and copy number variation studies were used to test for an enrichment of risk genes; in addition the genetic overlap with bipolar disorder identified through genome-wide association studies was used for validation. Gene sets with a common expression profile enriched for schizophrenia variants were used to identify biological pathways and assessed for their polygenic contribution to schizophrenia risk.The results of this thesis converged on a common developmental expression profile for schizophrenia risk genes. Genes identified with this profile were shown to harbour multiple, common risk variants for schizophrenia and were implicated in epigenetic processes relating to the regulation of gene transcription. Together this suggests that schizophrenia associated genes are involved in brain development, particularly during foetal stages, and may play a role in the regulation of this process." @default.
• W1525782170 created "2016-06-24" @default.
• W1525782170 creator A5018092286 @default.
• W1525782170 date "2013-01-01" @default.
• W1525782170 modified "2023-09-27" @default.
• W1525782170 title "Elucidating functional pathways associated with schizophrenia risk through analysis of brain gene expression" @default.
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