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Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia

RNA editing critically regulates neurodevelopment and normal neuronal function. We surveyed RNA editing across 364 schizophrenia cases and 383 control postmortem brain samples from the CommonMind Consortium, comprising two regions: dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex...

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Autores principales: Breen, Michael S., Dobbyn, Amanda, Li, Qin, Roussos, Panos, Hoffman, Gabriel E., Stahl, Eli, Chess, Andrew, Sklar, Pamela, Li, Jin Billy, Devlin, Bernie, Buxbaum, Joseph D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791127/
https://www.ncbi.nlm.nih.gov/pubmed/31455887
http://dx.doi.org/10.1038/s41593-019-0463-7
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author Breen, Michael S.
Dobbyn, Amanda
Li, Qin
Roussos, Panos
Hoffman, Gabriel E.
Stahl, Eli
Chess, Andrew
Sklar, Pamela
Li, Jin Billy
Devlin, Bernie
Buxbaum, Joseph D.
author_facet Breen, Michael S.
Dobbyn, Amanda
Li, Qin
Roussos, Panos
Hoffman, Gabriel E.
Stahl, Eli
Chess, Andrew
Sklar, Pamela
Li, Jin Billy
Devlin, Bernie
Buxbaum, Joseph D.
author_sort Breen, Michael S.
collection PubMed
description RNA editing critically regulates neurodevelopment and normal neuronal function. We surveyed RNA editing across 364 schizophrenia cases and 383 control postmortem brain samples from the CommonMind Consortium, comprising two regions: dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex. In schizophrenia, RNA editing sites in genes encoding AMPA-type glutamate receptors and post-synaptic density proteins were less edited, while those encoding translation initiation machinery were more edited. These sites replicate between brain regions, map to 3’UTR and intronic regions, share common sequence motifs, and map to binding sites for RNA binding proteins crucial for neurodevelopment. These findings cross-validate in hundreds of non-overlapping DLPFC samples. Furthermore, ~30% of RNA editing sites associate with cis-regulatory variants (edQTLs). Fine-mapping edQTLs with schizophrenia GWAS loci revealed co-localization of 11 edQTLs with 6 GWAS loci. Our findings demonstrate widespread altered RNA editing in schizophrenia and its genetic regulation, and suggest RNA editing mechanisms of schizophrenia neuropathology.
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spelling pubmed-67911272020-02-27 Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia Breen, Michael S. Dobbyn, Amanda Li, Qin Roussos, Panos Hoffman, Gabriel E. Stahl, Eli Chess, Andrew Sklar, Pamela Li, Jin Billy Devlin, Bernie Buxbaum, Joseph D. Nat Neurosci Article RNA editing critically regulates neurodevelopment and normal neuronal function. We surveyed RNA editing across 364 schizophrenia cases and 383 control postmortem brain samples from the CommonMind Consortium, comprising two regions: dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex. In schizophrenia, RNA editing sites in genes encoding AMPA-type glutamate receptors and post-synaptic density proteins were less edited, while those encoding translation initiation machinery were more edited. These sites replicate between brain regions, map to 3’UTR and intronic regions, share common sequence motifs, and map to binding sites for RNA binding proteins crucial for neurodevelopment. These findings cross-validate in hundreds of non-overlapping DLPFC samples. Furthermore, ~30% of RNA editing sites associate with cis-regulatory variants (edQTLs). Fine-mapping edQTLs with schizophrenia GWAS loci revealed co-localization of 11 edQTLs with 6 GWAS loci. Our findings demonstrate widespread altered RNA editing in schizophrenia and its genetic regulation, and suggest RNA editing mechanisms of schizophrenia neuropathology. 2019-08-27 2019-09 /pmc/articles/PMC6791127/ /pubmed/31455887 http://dx.doi.org/10.1038/s41593-019-0463-7 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Breen, Michael S.
Dobbyn, Amanda
Li, Qin
Roussos, Panos
Hoffman, Gabriel E.
Stahl, Eli
Chess, Andrew
Sklar, Pamela
Li, Jin Billy
Devlin, Bernie
Buxbaum, Joseph D.
Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia
title Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia
title_full Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia
title_fullStr Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia
title_full_unstemmed Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia
title_short Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia
title_sort global landscape and genetic regulation of rna editing in cortical samples from individuals with schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791127/
https://www.ncbi.nlm.nih.gov/pubmed/31455887
http://dx.doi.org/10.1038/s41593-019-0463-7
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