Investigation of Rare Single-Nucleotide PCDH15 Variants in Schizophrenia and Autism Spectrum Disorders.
PLoS One
; 11(4): e0153224, 2016.
Article
em En
| MEDLINE
| ID: mdl-27058588
ABSTRACT
Both schizophrenia (SCZ) and autism spectrum disorders (ASD) are neuropsychiatric disorders with overlapping genetic etiology. Protocadherin 15 (PCDH15), which encodes a member of the cadherin super family that contributes to neural development and function, has been cited as a risk gene for neuropsychiatric disorders. Recently, rare variants of large effect have been paid attention to understand the etiopathology of these complex disorders. Thus, we evaluated the impacts of rare, single-nucleotide variants (SNVs) in PCDH15 on SCZ or ASD. First, we conducted coding exon-targeted resequencing of PCDH15 with next-generation sequencing technology in 562 Japanese patients (370 SCZ and 192 ASD) and detected 16 heterozygous SNVs. We then performed association analyses on 2,096 cases (1,714 SCZ and 382 ASD) and 1,917 controls with six novel variants of these 16 SNVs. Of these six variants, four (p.R219K, p.T281A, p.D642N, c.3010-1G>C) were ultra-rare variants (minor allele frequency < 0.0005) that may increase disease susceptibility. Finally, no statistically significant association between any of these rare, heterozygous PCDH15 point variants and SCZ or ASD was found. Our results suggest that a larger sample size of resequencing subjects is necessary to detect associations between rare PCDH15 variants and neuropsychiatric disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Caderinas
/
Polimorfismo de Nucleotídeo Único
/
Transtorno do Espectro Autista
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão