AUTHOR=Wright Carrie , Calhoun Vince D. , Ehrlich Stefan , Wang Lei , Turner Jessica A. , Bizzozero Nora I. Perrone- 

TITLE=Meta gene set enrichment analyses link miR-137-regulated pathways with schizophrenia risk

JOURNAL=Frontiers in Genetics

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2015.00147

DOI=10.3389/fgene.2015.00147

ISSN=1664-8021

ABSTRACT=<p><bold>Background</bold>: A single nucleotide polymorphism (SNP) within <italic>MIR137</italic>, 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.</p><p><bold>Methods</bold>: 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.</p><p><bold>Results</bold>: 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.</p><p><bold>Conclusions</bold>: These results suggest that these biological pathways may be involved in the mechanisms by which this <italic>MIR137</italic> 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.</p>