Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia

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Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia

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dc.contributor.author Wright, C en_US
dc.contributor.author Gupta, C N en_US
dc.contributor.author Chen, J en_US
dc.contributor.author Patel, V en_US
dc.contributor.author Calhoun, V D en_US
dc.contributor.author Ehrlich, S en_US
dc.contributor.author Wang, L en_US
dc.contributor.author Bustillo, J R en_US
dc.contributor.author Perrone-Bizzozero, N I en_US
dc.contributor.author Turner, J A en_US
dc.date.accessioned 2016-06-14T18:52:26Z
dc.date.issued 2016 en_US
dc.identifier.citation Wright, C, C N Gupta, J Chen, V Patel, V D Calhoun, S Ehrlich, L Wang, J R Bustillo, N I Perrone-Bizzozero, and J A Turner. 2016. “Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia.” Translational Psychiatry 6 (2): e724. doi:10.1038/tp.2015.211. http://dx.doi.org/10.1038/tp.2015.211. en
dc.identifier.issn 2158-3188 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320362
dc.description.abstract Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis of schizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of a MIR137HG risk variant (rs1625579) in combination with variants in miR-137-regulated genes TCF4, PTGS2, MAPK1 and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessing schizophrenia risk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of these four schizophrenia risk-associated genes in 221 Caucasian subjects (89 schizophrenia patients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137-regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found that schizophrenia subjects homozygous for the MIR137HG risk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with the MIR137HG risk variant may influence GMC in schizophrenia-related regions in patients. Given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease. en
dc.language.iso en_US en
dc.publisher Nature Publishing Group en
dc.relation.isversionof doi:10.1038/tp.2015.211 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872419/pdf/ en
dash.license LAA en_US
dc.title Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Translational Psychiatry en
dc.date.available 2016-06-14T18:52:26Z

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