title: 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: Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94304, USA.
authors: Jianxin
authors: J
authors: Shi
authors: Douglas F
authors: DF
authors: Levinson
authors: Jubao
authors: J
authors: Duan
authors: Alan R
authors: AR
authors: Sanders
authors: Yonglan
authors: Y
authors: Zheng
authors: Itsik
authors: I
authors: Pe'er
authors: Frank
authors: F
authors: Dudbridge
authors: Peter A
authors: PA
authors: Holmans
authors: Alice S
authors: AS
authors: Whittemore
authors: Bryan J
authors: BJ
authors: Mowry
authors: Ann
authors: A
authors: Olincy
authors: Farooq
authors: F
authors: Amin
authors: C Robert
authors: CR
authors: Cloninger
authors: Jeremy M
authors: JM
authors: Silverman
authors: Nancy G
authors: NG
authors: Buccola
authors: William F
authors: WF
authors: Byerley
authors: Donald W
authors: DW
authors: Black
authors: Raymond R
authors: RR
authors: Crowe
authors: Jorge R
authors: JR
authors: Oksenberg
authors: Daniel B
authors: DB
authors: Mirel
authors: Kenneth S
authors: KS
authors: Kendler
authors: Robert
authors: R
authors: Freedman
authors: Pablo V
authors: PV
authors: Gejman
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000276:immunology