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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-07-01

AUTHORS

Jianxin Shi, Douglas F. Levinson, Jubao Duan, Alan R. Sanders, Yonglan Zheng, Itsik Pe’er, Frank Dudbridge, Peter A. Holmans, Alice S. Whittemore, Bryan J. Mowry, Ann Olincy, Farooq Amin, C. Robert Cloninger, Jeremy M. Silverman, Nancy G. Buccola, William F. Byerley, Donald W. Black, Raymond R. Crowe, Jorge R. Oksenberg, Daniel B. Mirel, Kenneth S. Kendler, Robert Freedman, Pablo V. Gejman

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. More... »

PAGES

753

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature08192

DOI

http://dx.doi.org/10.1038/nature08192

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022261447

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19571809


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