SIRPB1 copy-number polymorphism as candidate quantitative trait locus for impulsive-disinhibited personality.
Genes Brain Behav
; 13(7): 653-62, 2014 Sep.
Article
en En
| MEDLINE
| ID: mdl-25039969
Impulsive-disinhibited personality (IDP) is a behavioral trait mainly characterized by seeking immediate gratification at the expense of more enduring or long-term gains. This trait has a major role in the development of several disinhibitory behaviors and syndromes, including psychopathy, attention-deficit and hyperactivity disorder, cluster-B personality disorders, criminality and alcoholism. Available data consistently support a strong heritable component, accounting for 30-60% of the observed variance in personality traits. A genome-wide analysis of copy-number variants was designed to identify novel genetic pathways associated with the IDP trait, using a series of 261 male participants with maximized opposite IDP scores. Quantitative trait locus analysis of candidate copy-number variants (CNVs) was conducted across the entire IDP continuum. Functional effects of associated variants were evaluated in zebrafish embryos. A common CNV mapping to the immune-related gene SIRPB1 was significantly associated with IDP scores in a dose-dependent manner (ß=-0.172, P<0.017). Expression quantitative trait locus analysis of the critical region revealed higher SIRPB1 mRNA levels associated with the haplotype containing the deleted allele (P<0.0007). Epigenetic marks highlighted the presence of two potential insulators within the deleted region, confirmed by functional assays in zebrafish embryos, which suggests that SIRPB1 expression rates are affected by the presence/absence of the insulator regions. Upregulation of SIRPB1 has been described in prefrontal cortex of patients with schizophrenia, providing a link between SIRPB1 and diseases involving disinhibition and failure to control impulsivity. We propose SIRPB1 as a novel candidate gene to account for phenotypic differences observed in the IDP trait.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Superficie Celular
/
Sitios de Carácter Cuantitativo
/
Variaciones en el Número de Copia de ADN
/
Conducta Impulsiva
/
Inhibición Psicológica
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Genes Brain Behav
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
GENETICA
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Reino Unido