Schizophrenia risk variants affecting microRNA function and site-specific regulation of NT5C2 by miR-206.
Eur Neuropsychopharmacol
; 26(9): 1522-1526, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27424800
ABSTRACT
Despite the identification of numerous schizophrenia-associated genetic variants, few have been examined functionally to identify and characterize the causal variants. To mitigate this, we aimed at identifying functional variants affecting miRNA function. Using data from a large-scale genome-wide association study of schizophrenia, we looked for schizophrenia risk variants altering either miRNA binding sites, miRNA genes, promoters for miRNA genes, or variants that were expression quantitative trait loci (eQTLs) for miRNA genes. We hereby identified several potentially functional variants relating to miRNA function with our top finding being a schizophrenia protective allele that disrupts miR-206׳s binding to NT5C2 thus leading to increased expression of this gene. A subsequent experimental follow-up of the variant using a luciferase-based reporter assay confirmed that the allele disrupts the binding. Our study therefore suggests that miR-206 may contribute to schizophrenia risk through allele-dependent regulation of the genome-wide significant gene NT5C2.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
5'-Nucleotidase
/
Polimorfismo de Nucleotídeo Único
/
MicroRNAs
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Eur Neuropsychopharmacol
Assunto da revista:
PSICOFARMACOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article