Common variants on chromosome 6p22.1 are associated with schizophrenia.
Nature
; 460(7256): 753-7, 2009 Aug 06.
Article
en En
| MEDLINE
| ID: mdl-19571809
ABSTRACT
Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5-1%, with high heritability (80-85%) and complex transmission. Recent studies implicate rare, large, high-penetrance copy number variants in some cases, but the genes or biological mechanisms that underlie susceptibility are not known. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended major histocompatibility complex region on chromosome 6. We carried out a genome-wide association study of common SNPs in the Molecular Genetics of Schizophrenia (MGS) case-control sample, and then a meta-analysis of data from the MGS, International Schizophrenia Consortium and SGENE data sets. No MGS finding achieved genome-wide statistical significance. In the meta-analysis of European-ancestry subjects (8,008 cases, 19,077 controls), significant association with schizophrenia was observed in a region of linkage disequilibrium on chromosome 6p22.1 (P = 9.54 x 10(-9)). This region includes a histone gene cluster and several immunity-related genes--possibly implicating aetiological mechanisms involving chromatin modification, transcriptional regulation, autoimmunity and/or infection. These results demonstrate that common schizophrenia susceptibility alleles can be detected. The characterization of these signals will suggest important directions for research on susceptibility mechanisms.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Esquizofrenia
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Cromosomas Humanos Par 6
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Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
Tipo de estudio:
Observational_studies
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Risk_factors_studies
/
Systematic_reviews
Límite:
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
Nature
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos