Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature neuroscience, 2019-09, Vol.22 (9), p.1402

Ort / Verlag

United States

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• RNA editing critically regulates neurodevelopment and normal neuronal function. The global landscape of RNA editing was surveyed across 364 schizophrenia cases and 383 control postmortem brain samples from the CommonMind Consortium, comprising two regions: dorsolateral prefrontal cortex and anterior cingulate cortex. In schizophrenia, RNA editing sites in genes encoding AMPA-type glutamate receptors and postsynaptic density proteins were less edited, whereas those encoding translation initiation machinery were edited more. These sites replicate between brain regions, map to 3'-untranslated regions and intronic regions, share common sequence motifs and overlap with binding sites for RNA-binding proteins crucial for neurodevelopment. These findings cross-validate in hundreds of non-overlapping dorsolateral prefrontal cortex samples. Furthermore, ~30% of RNA editing sites associate with cis-regulatory variants (editing quantitative trait loci or edQTLs). Fine-mapping edQTLs with schizophrenia risk loci revealed co-localization of eleven edQTLs with six loci. The findings demonstrate widespread altered RNA editing in schizophrenia and its genetic regulation, and suggest a causal and mechanistic role of RNA editing in schizophrenia neuropathology.