Publication Date:
2009-07-03
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775422/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775422/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shi, Jianxin -- Levinson, Douglas F -- Duan, Jubao -- Sanders, Alan R -- Zheng, Yonglan -- Pe'er, Itsik -- Dudbridge, Frank -- Holmans, Peter A -- Whittemore, Alice S -- Mowry, Bryan J -- Olincy, Ann -- Amin, Farooq -- Cloninger, C Robert -- Silverman, Jeremy M -- Buccola, Nancy G -- Byerley, William F -- Black, Donald W -- Crowe, Raymond R -- Oksenberg, Jorge R -- Mirel, Daniel B -- Kendler, Kenneth S -- Freedman, Robert -- Gejman, Pablo V -- MC_U105292688/Medical Research Council/United Kingdom -- R01 AG037132/AG/NIA NIH HHS/ -- R01 MH059565/MH/NIMH NIH HHS/ -- R01 MH059565-08/MH/NIMH NIH HHS/ -- R01 MH059566/MH/NIMH NIH HHS/ -- R01 MH059566-08/MH/NIMH NIH HHS/ -- R01 MH059571/MH/NIMH NIH HHS/ -- R01 MH059571-08/MH/NIMH NIH HHS/ -- R01 MH059571-08S1/MH/NIMH NIH HHS/ -- R01 MH059586/MH/NIMH NIH HHS/ -- R01 MH059586-08/MH/NIMH NIH HHS/ -- R01 MH059587-09/MH/NIMH NIH HHS/ -- R01 MH059588-08/MH/NIMH NIH HHS/ -- R01 MH060870-09/MH/NIMH NIH HHS/ -- R01 MH060879/MH/NIMH NIH HHS/ -- R01 MH060879-08/MH/NIMH NIH HHS/ -- R01 MH061675/MH/NIMH NIH HHS/ -- R01 MH061675-09/MH/NIMH NIH HHS/ -- R01 MH061675-09S1/MH/NIMH NIH HHS/ -- R01 MH067257-04S1/MH/NIMH NIH HHS/ -- R01 MH081800/MH/NIMH NIH HHS/ -- R01 MH081800-01/MH/NIMH NIH HHS/ -- U01 MH046276/MH/NIMH NIH HHS/ -- U01 MH046276-08/MH/NIMH NIH HHS/ -- U01 MH046289-08/MH/NIMH NIH HHS/ -- U01 MH046318/MH/NIMH NIH HHS/ -- U01 MH046318-08/MH/NIMH NIH HHS/ -- U01 MH079469/MH/NIMH NIH HHS/ -- U01 MH079469-03/MH/NIMH NIH HHS/ -- U01 MH079470/MH/NIMH NIH HHS/ -- U01 MH079470-02/MH/NIMH NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- U54 RR020278-05/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Aug 6;460(7256):753-7. doi: 10.1038/nature08192. Epub 2009 Jul 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571809" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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