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

@article{citeulike:5103476, abstract = {Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1\%, with high heritability (80–85\%) and complex transmission1. Recent studies implicate rare, large, high-penetrance copy number variants in some cases2, 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  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.}, author = {Shi, Jianxin and Levinson, Douglas F. and Duan, Jubao and Sanders, Alan R. and Zheng, Yonglan and Pe\^{a}€™er, Itsik and Dudbridge, Frank and Holmans, Peter A. and Whittemore, Alice S. and Mowry, Bryan J. and Olincy, Ann and Amin, Farooq and Cloninger, C. Robert and Silverman, Jeremy M. and Buccola, Nancy G. and Byerley, William F. and Black, Donald W. and Crowe, Raymond R. and Oksenberg, Jorge R. and Mirel, Daniel B. and Kendler, Kenneth S. and Freedman, Robert and Gejman, Pablo V.}, citeulike-article-id = {5103476}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature08192}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature08192}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19571809}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19571809}, day = {01}, doi = {10.1038/nature08192}, issn = {0028-0836}, journal = {Nature}, keywords = {association, schizophrenia, sv}, month = {July}, number = {7256}, pages = {753--757}, posted-at = {2009-08-05 20:02:07}, priority = {2}, publisher = {Nature Publishing Group}, title = {Common variants on chromosome 6p22.1 are associated with schizophrenia}, url = {http://dx.doi.org/10.1038/nature08192}, volume = {460}, year = {2009} }

TY - JOUR ID - citeulike:5103476 L3 - citeulike-article-id:5103476 N2 - Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5–1%, with high heritability (80–85%) and complex transmission1. Recent studies implicate rare, large, high-penetrance copy number variants in some cases2, 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  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. IS - 7256 JF - Nature SN - 0028-0836 EP - 757 TI - Common variants on chromosome 6p22.1 are associated with schizophrenia PB - Nature Publishing Group VL - 460 SP - 753 KW - association KW - schizophrenia KW - sv AU - Shi, Jianxin AU - Levinson, Douglas AU - Duan, Jubao AU - Sanders, Alan AU - Zheng, Yonglan AU - Pe’er, Itsik AU - Dudbridge, Frank AU - Holmans, Peter AU - Whittemore, Alice AU - Mowry, Bryan AU - Olincy, Ann AU - Amin, Farooq AU - Cloninger, Robert AU - Silverman, Jeremy AU - Buccola, Nancy AU - Byerley, William AU - Black, Donald AU - Crowe, Raymond AU - Oksenberg, Jorge AU - Mirel, Daniel AU - Kendler, Kenneth AU - Freedman, Robert AU - Gejman, Pablo PY - 2009/07/01/ UR - http://dx.doi.org/10.1038/nature08192 ER -