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Common variants on chromosome 6p22.1 are associated with schizophrenia

Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1%, with high heritability (80–85%) and complex transmission.1 Recent studies implicate rare, large, high-penetrance copy number variants (CNVs) in some cases2, but it is not known what genes or biological mechanisms underlie...

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Autores principales: Shi, Jianxin, Levinson, Douglas F., Duan, Jubao, Sanders, Alan R., Zheng, Yonglan, Pe'er, Itsik, Dudbridge, Frank, Holmans, Peter A., Whittemore, Alice S., Mowry, Bryan J., Olincy, Ann, Amin, Farooq, Cloninger, C. Robert, Silverman, Jeremy M., Buccola, Nancy G., Byerley, William F., Black, Donald W., Crowe, Raymond R., Oksenberg, Jorge R., Mirel, Daniel B., Kendler, Kenneth S., Freedman, Robert, Gejman, Pablo V.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775422/
https://www.ncbi.nlm.nih.gov/pubmed/19571809
http://dx.doi.org/10.1038/nature08192
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author Shi, Jianxin
Levinson, Douglas F.
Duan, Jubao
Sanders, Alan R.
Zheng, Yonglan
Pe'er, Itsik
Dudbridge, Frank
Holmans, Peter A.
Whittemore, Alice S.
Mowry, Bryan J.
Olincy, Ann
Amin, Farooq
Cloninger, C. Robert
Silverman, Jeremy M.
Buccola, Nancy G.
Byerley, William F.
Black, Donald W.
Crowe, Raymond R.
Oksenberg, Jorge R.
Mirel, Daniel B.
Kendler, Kenneth S.
Freedman, Robert
Gejman, Pablo V.
author_facet Shi, Jianxin
Levinson, Douglas F.
Duan, Jubao
Sanders, Alan R.
Zheng, Yonglan
Pe'er, Itsik
Dudbridge, Frank
Holmans, Peter A.
Whittemore, Alice S.
Mowry, Bryan J.
Olincy, Ann
Amin, Farooq
Cloninger, C. Robert
Silverman, Jeremy M.
Buccola, Nancy G.
Byerley, William F.
Black, Donald W.
Crowe, Raymond R.
Oksenberg, Jorge R.
Mirel, Daniel B.
Kendler, Kenneth S.
Freedman, Robert
Gejman, Pablo V.
author_sort Shi, Jianxin
collection PubMed
description Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1%, with high heritability (80–85%) and complex transmission.1 Recent studies implicate rare, large, high-penetrance copy number variants (CNVs) in some cases2, but it is not known what genes or biological mechanisms underlie susceptibility. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended Major Histocompatibility Complex (MHC) region on chromosome 6. We carried out a genome-wide association study (GWAS) 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 (ISC) and SGENE datasets. 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 × 10(−9)). This region includes a histone gene cluster and several immunity-related genes, possibly implicating etiologic mechanisms involving chromatin modification, transcriptional regulation, auto-immunity 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.
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spelling pubmed-27754222010-02-07 Common variants on chromosome 6p22.1 are associated with schizophrenia Shi, Jianxin Levinson, Douglas F. Duan, Jubao Sanders, Alan R. Zheng, Yonglan Pe'er, Itsik Dudbridge, Frank Holmans, Peter A. Whittemore, Alice S. Mowry, Bryan J. Olincy, Ann Amin, Farooq Cloninger, C. Robert Silverman, Jeremy M. Buccola, Nancy G. Byerley, William F. Black, Donald W. Crowe, Raymond R. Oksenberg, Jorge R. Mirel, Daniel B. Kendler, Kenneth S. Freedman, Robert Gejman, Pablo V. Nature Article Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1%, with high heritability (80–85%) and complex transmission.1 Recent studies implicate rare, large, high-penetrance copy number variants (CNVs) in some cases2, but it is not known what genes or biological mechanisms underlie susceptibility. Here we show that schizophrenia is significantly associated with single nucleotide polymorphisms (SNPs) in the extended Major Histocompatibility Complex (MHC) region on chromosome 6. We carried out a genome-wide association study (GWAS) 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 (ISC) and SGENE datasets. 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 × 10(−9)). This region includes a histone gene cluster and several immunity-related genes, possibly implicating etiologic mechanisms involving chromatin modification, transcriptional regulation, auto-immunity 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. 2009-07-01 2009-08-06 /pmc/articles/PMC2775422/ /pubmed/19571809 http://dx.doi.org/10.1038/nature08192 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shi, Jianxin
Levinson, Douglas F.
Duan, Jubao
Sanders, Alan R.
Zheng, Yonglan
Pe'er, Itsik
Dudbridge, Frank
Holmans, Peter A.
Whittemore, Alice S.
Mowry, Bryan J.
Olincy, Ann
Amin, Farooq
Cloninger, C. Robert
Silverman, Jeremy M.
Buccola, Nancy G.
Byerley, William F.
Black, Donald W.
Crowe, Raymond R.
Oksenberg, Jorge R.
Mirel, Daniel B.
Kendler, Kenneth S.
Freedman, Robert
Gejman, Pablo V.
Common variants on chromosome 6p22.1 are associated with schizophrenia
title Common variants on chromosome 6p22.1 are associated with schizophrenia
title_full Common variants on chromosome 6p22.1 are associated with schizophrenia
title_fullStr Common variants on chromosome 6p22.1 are associated with schizophrenia
title_full_unstemmed Common variants on chromosome 6p22.1 are associated with schizophrenia
title_short Common variants on chromosome 6p22.1 are associated with schizophrenia
title_sort common variants on chromosome 6p22.1 are associated with schizophrenia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775422/
https://www.ncbi.nlm.nih.gov/pubmed/19571809
http://dx.doi.org/10.1038/nature08192
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