Association of SNPs in EGR3 and ARC with Schizophrenia Supports a Biological Pathway for Schizophrenia Risk
| Autor: | Rebecca Reiman, Alexandre A. Todorov, Matthew J. Huentelman, Leela Muppana, Matt De Both, C. Robert Cloninger, Jeremy J. Pruzin, Valentin Dinu, Jason J. Corneveaux, Cassie N. Borish, Jie Ma, Amber Ahmed, Rui Zhang, Amelia L. Gallitano |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
China Genotyping Techniques Population lcsh:Medicine Genome-wide association study Single-nucleotide polymorphism Nerve Tissue Proteins Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Asian People Risk Factors medicine SNP media_common.cataloged_instance Humans European union lcsh:Science education Early Growth Response Protein 3 030304 developmental biology media_common Genetics 0303 health sciences education.field_of_study Multidisciplinary Arc (protein) lcsh:R High-Throughput Nucleotide Sequencing Tag SNP medicine.disease 3. Good health Cytoskeletal Proteins Schizophrenia lcsh:Q Female 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 10, p e0135076 (2015) |
| ISSN: | 1932-6203 |
| Popis: | We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3, and its target ARC, should influence schizophrenia susceptibility. We used a pooled Next-Generation Sequencing approach to identify variants across these genes in U.S. populations of European (EU) and African (AA) descent. Three EGR3 and one ARC SNP were selected and genotyped for validation, and three SNPs were tested for association in a replication cohort. In the EU group of 386 schizophrenia cases and 150 controls EGR3 SNP rs1877670 and ARC SNP rs35900184 showed significant associations (p = 0.0078 and p = 0.0275, respectively). In the AA group of 185 cases and 50 controls, only the ARC SNP revealed significant association (p = 0.0448). The ARC SNP did not show association in the Han Chinese (CH) population. However, combining the EU, AA, and CH groups revealed a highly significant association of ARC SNP rs35900184 (p = 2.353 x 10(-7); OR [95% CI] = 1.54 [1.310-1.820]). These findings support previously reported associations between EGR3 and schizophrenia. Moreover, this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk. These results support the need for further investigation of the proposed pathway of environmentally responsive, synaptic plasticity-related, schizophrenia genes. |
| Databáze: | OpenAIRE |
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