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

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.

• 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
• Journal: Nature (Nature) Vol. 460 Issue 7256 Pg. 753-7 (Aug 06 2009) ISSN: 1476-4687 [Electronic] England
• PMID: 19571809 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Alleles
• Case-Control Studies
• Chromosomes, Human, Pair 6 (genetics)
• Europe (ethnology)
• Genetic Predisposition to Disease (genetics)
• Genome, Human (genetics)
• Genome-Wide Association Study
• Humans
• Linkage Disequilibrium (genetics)
• Major Histocompatibility Complex (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Schizophrenia (genetics, immunology)