TY - JOUR
T1 - Common variants on chromosome 6p22.1 are associated with schizophrenia
AU - Shi, Jianxin
AU - Levinson, Douglas F.
AU - Duan, Jubao
AU - Sanders, Alan R.
AU - Zheng, Yonglan
AU - Péer, Itsik
AU - Dudbridge, Frank
AU - Holmans, Peter A.
AU - Whittemore, Alice S.
AU - Mowry, Bryan J.
AU - Olincy, Ann
AU - Amin, Farooq
AU - Cloninger, C. Robert
AU - Silverman, Jeremy M.
AU - Buccola, Nancy G.
AU - Byerley, William F.
AU - Black, Donald W.
AU - Crowe, Raymond R.
AU - Oksenberg, Jorge R.
AU - Mirel, Daniel B.
AU - Kendler, Kenneth S.
AU - Freedman, Robert
AU - Gejman, Pablo V.
N1 - Funding Information:
Acknowledgements We thank the study participants, and the research staff at the study sites. This study was supported by funding from the National Institute of Mental Health (USA) and the National Alliance for Research on Schizophrenia and Depression. Genotyping of part of the sample was supported by the Genetic Association Information Network (GAIN), and by The Paul Michael Donovan Charitable Foundation. Genotyping was carried out by the Center for Genotyping and Analysis at the Broad Institute of Harvard and MIT with support from the National Center for Research Resources (USA). The GAIN quality control team (G. R. Abecasis and J. Paschall) made important contributions to the project. We thank S. Purcell for assistance with PLINK.
PY - 2009/8/6
Y1 - 2009/8/6
N2 - Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5ĝ€"1%, with high heritability (80ĝ€"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 × 10-9). This region includes a histone gene cluster and several immunity-related genesĝ€"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.
AB - Schizophrenia, a devastating psychiatric disorder, has a prevalence of 0.5ĝ€"1%, with high heritability (80ĝ€"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 × 10-9). This region includes a histone gene cluster and several immunity-related genesĝ€"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.
UR - http://www.scopus.com/inward/record.url?scp=68449096727&partnerID=8YFLogxK
U2 - 10.1038/nature08192
DO - 10.1038/nature08192
M3 - Article
C2 - 19571809
AN - SCOPUS:68449096727
SN - 0028-0836
VL - 460
SP - 753
EP - 757
JO - Nature
JF - Nature
IS - 7256
ER -