Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia.
Am J Med Genet B Neuropsychiatr Genet
; 171B(3): 447-57, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26852906
ABSTRACT
Chromosome 22q11.2 deletion syndrome and genetic variations including single-nucleotide polymorphism (SNP) and copy number variation (CNV) in catechol-O-methyltransferase (COMT) situated at 22q11.2 remains controversial. Here, the genetic relationship between COMT and Japanese patients with schizophrenia was investigated by examining whether the SNPs correlated with schizophrenia based on a common disease-common variant hypothesis. Additionally, 22q11.2DS were screened based on a common disease-rare variant hypothesis; low-frequency CNVs situated at two COMT promoters and exons were investigated based on the low-frequency variants with an intermediate effect; and positive findings from the first stage were reconfirmed using a second-stage replication study including a larger sample size. Eight SNPs and 10 CNVs were investigated using Taqman SNP and CNV quantitative real-time polymerase chain reaction method. For the first-stage analysis, 513 unrelated Japanese patients with schizophrenia and 705 healthy controls were examined. For the second-stage replication study, positive findings from the first stage were further investigated using a larger sample size, namely 1,854 patients with schizophrenia and 2,137 controls. The first-stage analysis showed significant associations among schizophrenia, intronic SNP rs165774, CNV6 situated at promoter 1, CNV8 at exon 6, and CNV9 at exon 7. The second-stage study showed that intronic SNP rs165774 (χ(2) = 8.327, P = 0.0039), CNV6 (χ(2) = 19.66, P = 0.00005), and CNV8 (χ(2) = 16.57, P = 0.00025) were significantly associated with schizophrenia. Large and rare CNVs as well as low-frequency CNVs and relatively small CNVs, namely <30 kb in COMT, may be genetic risk factors for schizophrenia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Biossíntese de Proteínas
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Catecol O-Metiltransferase
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Regiões Promotoras Genéticas
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Povo Asiático
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Estudos de Associação Genética
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Variações do Número de Cópias de DNA
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Med Genet B Neuropsychiatr Genet
Assunto da revista:
GENETICA MEDICA
/
NEUROLOGIA
/
PSIQUIATRIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão