Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia Risk
Background: A single nucleotide polymorphism (SNP) within MIR137, the host gene for miR-137, has been identified repeatedly as a risk factor for schizophrenia. Previous genetic pathway analyses suggest that potential targets of this microRNA (miRNA) are also highly enriched in schizophrenia-relevan...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2015.00147/full |
| _version_ | 1818889792596738048 |
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| author | Carrie eWright Vince D Calhoun Vince D Calhoun Stefan eEhrlich Lei eWang Jessica A Turner Jessica A Turner Nora Irma Perrone-Bizzozero |
| author_facet | Carrie eWright Vince D Calhoun Vince D Calhoun Stefan eEhrlich Lei eWang Jessica A Turner Jessica A Turner Nora Irma Perrone-Bizzozero |
| author_sort | Carrie eWright |
| collection | DOAJ |
| description | Background: A single nucleotide polymorphism (SNP) within MIR137, the host gene for miR-137, has been identified repeatedly as a risk factor for schizophrenia. Previous genetic pathway analyses suggest that potential targets of this microRNA (miRNA) are also highly enriched in schizophrenia-relevant biological pathways, including those involved in nervous system development and function. Methods: In this study, we evaluated the schizophrenia risk of miR-137 target genes within these pathways. Gene set enrichment analysis of pathway-specific miR-137 targets was performed using the stage 1 (21,856 subjects) schizophrenia genome wide association study data from the Psychiatric Genomics Consortium and a small independent replication cohort (244 subjects) from the Mind Clinical Imaging Consortium and Northwestern University.Results: Gene sets of potential miR-137 targets were enriched with variants associated with schizophrenia risk, including target sets involved in axonal guidance signaling, Ephrin receptor signaling, long-term potentiation, PKA signaling, and Sertoli cell junction signaling. The schizophrenia-risk association of SNPs in PKA signaling targets was replicated in the second independent cohort. Conclusions: These results suggest that these biological pathways may be involved in the mechanisms by which this MIR137 variant enhances schizophrenia risk. SNPs in targets and the miRNA host gene may collectively lead to dysregulation of target expression and aberrant functioning of such implicated pathways. Pathway-guided gene set enrichment analyses should be useful in evaluating the impact of other miRNAs and target genes in different diseases. |
| first_indexed | 2024-12-19T17:14:39Z |
| format | Article |
| id | doaj.art-b068de72f43e482d9da5827f44c528d5 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-19T17:14:39Z |
| publishDate | 2015-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-b068de72f43e482d9da5827f44c528d52022-12-21T20:12:56ZengFrontiers Media S.A.Frontiers in Genetics1664-80212015-04-01610.3389/fgene.2015.00147128406Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia RiskCarrie eWright0Vince D Calhoun1Vince D Calhoun2Stefan eEhrlich3Lei eWang4Jessica A Turner5Jessica A Turner6Nora Irma Perrone-Bizzozero7University of New MexicoUniversity of New MexicoMind Research NetworkTechnische UniversitätNorthwestern UniversityGeorgia State UniversityMind Research NetworkUniversity of New MexicoBackground: A single nucleotide polymorphism (SNP) within MIR137, the host gene for miR-137, has been identified repeatedly as a risk factor for schizophrenia. Previous genetic pathway analyses suggest that potential targets of this microRNA (miRNA) are also highly enriched in schizophrenia-relevant biological pathways, including those involved in nervous system development and function. Methods: In this study, we evaluated the schizophrenia risk of miR-137 target genes within these pathways. Gene set enrichment analysis of pathway-specific miR-137 targets was performed using the stage 1 (21,856 subjects) schizophrenia genome wide association study data from the Psychiatric Genomics Consortium and a small independent replication cohort (244 subjects) from the Mind Clinical Imaging Consortium and Northwestern University.Results: Gene sets of potential miR-137 targets were enriched with variants associated with schizophrenia risk, including target sets involved in axonal guidance signaling, Ephrin receptor signaling, long-term potentiation, PKA signaling, and Sertoli cell junction signaling. The schizophrenia-risk association of SNPs in PKA signaling targets was replicated in the second independent cohort. Conclusions: These results suggest that these biological pathways may be involved in the mechanisms by which this MIR137 variant enhances schizophrenia risk. SNPs in targets and the miRNA host gene may collectively lead to dysregulation of target expression and aberrant functioning of such implicated pathways. Pathway-guided gene set enrichment analyses should be useful in evaluating the impact of other miRNAs and target genes in different diseases.http://journal.frontiersin.org/Journal/10.3389/fgene.2015.00147/fullSchizophreniamicroRNApathway analysismiR-137PKA signalingGene set enrichment analysis (GSEA) |
| spellingShingle | Carrie eWright Vince D Calhoun Vince D Calhoun Stefan eEhrlich Lei eWang Jessica A Turner Jessica A Turner Nora Irma Perrone-Bizzozero Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia Risk Frontiers in Genetics Schizophrenia microRNA pathway analysis miR-137 PKA signaling Gene set enrichment analysis (GSEA) |
| title | Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia Risk |
| title_full | Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia Risk |
| title_fullStr | Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia Risk |
| title_full_unstemmed | Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia Risk |
| title_short | Meta Gene Set Enrichment Analyses Link miR-137-regulated Pathways with Schizophrenia Risk |
| title_sort | meta gene set enrichment analyses link mir 137 regulated pathways with schizophrenia risk |
| topic | Schizophrenia microRNA pathway analysis miR-137 PKA signaling Gene set enrichment analysis (GSEA) |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2015.00147/full |
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