Association Strength Gene Ontology analysis
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Schizophrenia is a psychiatric disorder marked by delusions, hallucinations, flat affect and disorganized thinking. After decades of research on schizophrenia its etiology remains elusive. Psychiatry, neuroimaging, molecular biology and other fields have provided several theories about schizophrenia that all seem to explain a part of the whole etiology. Because schizophrenia has a large heritable component, genetic studies such as genome wide association studies (GWAS) are frequently adopted to pinpoint genetic variance that increase the chance to develop schizophrenia. Identification of genetic variance that increases the chance to develop schizophrenia helps to understand the etiology of schizophrenia and can provide valuable targets for treatment. Despite the promising aspects of this approach, it holds many caveats and challenges. For example, GWAS on schizophrenia are hindered by large quantities of small effect common genetic variance that emerges from the heterogeneity, polygeneity and fuzzy diagnostical boundaries of schizophrenia. This creates ‘noise’ that makes it hard to find significant and replicable associations between genes and schizophrenia. Nonetheless, small effect common genetic variance from GWAS data can be used to identify biological mechanisms involved in schizophrenia, using appropriate statistical methods. One of those methods is called ‘Gene Ontology analysis’. This analysis applies prior biological knowledge to GWAS results to identify pathways, biological processes, molecular processes and cellular components that are associated with the trait of interest. This study has two aims: 1. To develop a Gene Ontology analysis that is especially suitable for GWAS by incorporating the association strength (AS) of each gene in the analysis. 2. To use this ‘AS Gene Ontology analysis’ on GWAS data and assess whether one or more of the current theories about the etiology of schizophrenia is particularly supported. First an introduction about schizophrenia is given and some popular theories about its etiology are described. Then the caveats and challenges of GWAS studies on schizophrenia are described followed by information on Gene Ontology analysis and arguments for its improvement in this study. This is followed by the methodology, results and conclusions of this study.