Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia
| Autor: | Quanwei Zhang, Rubén Nogales-Cadenas, Jhih Rong Lin, Wen Zhang, Ying Cai, Zhengdong D. Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Disease gene Genetics Schizophrenia (object-oriented programming) Disease mechanisms Epigenetics of schizophrenia Genome-wide association study Investigations Biology Polymorphism Single Nucleotide Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Genetic Loci mental disorders Schizophrenia Humans Genetic Predisposition to Disease Gene 030217 neurology & neurosurgery Genome-Wide Association Study Genetic association |
| Zdroj: | Genetics. 204:1587-1600 |
| ISSN: | 1943-2631 |
| DOI: | 10.1534/genetics.116.187195 |
| Popis: | Schizophrenia is a severe mental disorder with a large genetic component. Recent genome-wide association studies (GWAS) have identified many schizophrenia-associated common variants. For most of the reported associations, however, the underlying biological mechanisms are not clear. The critical first step for their elucidation is to identify the most likely disease genes as the source of the association signals. Here, we describe a general computational framework of post-GWAS analysis for complex disease gene prioritization. We identify 132 putative schizophrenia risk genes in 76 risk regions spanning 120 schizophrenia-associated common variants, 78 of which have not been recognized as schizophrenia disease genes by previous GWAS. Even more significantly, 29 of them are outside the risk regions, likely under regulation of transcriptional regulatory elements contained therein. These putative schizophrenia risk genes are transcriptionally active in both brain and the immune system, and highly enriched among cellular pathways, consistent with leading pathophysiological hypotheses about the pathogenesis of schizophrenia. With their involvement in distinct biological processes, these putative schizophrenia risk genes, with different association strengths, show distinctive temporal expression patterns, and play specific biological roles during brain development. |
| Databáze: | OpenAIRE |
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