Background
We performed a genome-wide association study (GWAS) to identify common risk variants
for schizophrenia.
Methods
The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339
directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of
this sample (270 cases and 860 controls) was subsequently included in the Psychiatric
GWAS Consortium-schizophrenia GWAS meta-analysis.
Results
One hundred eight SNPs were taken forward for replication in an independent sample
of 13,195 cases and 31,021 control subjects. The most significant associations in
discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10−9 and in combined samples (rs2523722 p combined = 2.88 × 10−16) mapped to the major histocompatibility complex (MHC) region. We imputed classical
human leukocyte antigen (HLA) alleles at the locus; the most significant finding was
with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles
DRB1*03:01 and B*08:01 were protective, replicating a previous study.
Conclusions
This study provides further support for involvement of MHC class I molecules in schizophrenia.
We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.
Key Words
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Article info
Publication history
Published online: August 10, 2012
Received in revised form:
May 1,
2012
Received:
January 12,
2012
Footnotes
Address correspondence to Aiden Corvin, M.D., Ph.D., Trinity Centre for Health Sciences, Department of Psychiatry, St. James's Hospital, Dublin 8, Ireland; E-mail: [email protected]
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- The Genes in the Major Histocompatibility Complex as Risk Factors for Schizophrenia: De Omnibus DubitandumBiological PsychiatryVol. 72Issue 8
- PreviewThe major histocompatibility complex (MHC) is an approximately 4 megabase region located on the short arm of chromosome 6 (6p21); it is also known as the human leukocyte antigen (HLA) superlocus. MHC encodes the classical and transplantation HLA genes and many other genes with essential roles for immune function and cellular processes including genes that are important for nervous system development and function. Although the MHC represents only a very small part (about .1%) of the human genome its properties can easily be described as extreme and intricate: most complex, most gene dense, most polymorphic, second largest contiguous sequence, containing the most disease associations, and most difficult to analyze.
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