Background
Patients with schizophrenia often suffer from cognitive dysfunction, including impaired
learning and memory. We recently demonstrated that long-term potentiation in rat hippocampus,
a mechanistic model of learning and memory, is linked to gene expression changes in
immunity-related processes involved in complement activity and antigen presentation.
We therefore aimed to examine whether key regulators of these processes are genetic
susceptibility factors in schizophrenia.
Methods
Analysis of genetic association was based on data mining of genotypes from a German
genome-wide association study and a multiplex GoldenGate tag single nucleotide polymorphism
(SNP)-based assay of Norwegian and Danish case–control samples (Scandinavian Collaboration
on Psychiatric Etiology), including 1133 patients with schizophrenia and 2444 healthy
control subjects.
Results
Allelic associations were found across all three samples for eight common SNPs in
the complement control-related gene CSMD2 (CUB and Sushi Multiple Domains 2) on chromosome 1p35.1-34.3, of which rs911213 reached a statistical significance
comparable to that of a genome wide threshold (p value = 4.0 × 10−8; odd ratio = .73, 95% confidence interval = .65–.82). The second most significant
gene was CSMD1 on chromosome 8p23.2, a homologue to CSMD2. In addition, we observed replicated associations in the complement surface receptor
CD46 as well as the major histocompatibility complex genes HLA-DMB and HLA-DOA.
Conclusions
These data demonstrate a significant role of complement control-related genes in the
etiology of schizophrenia and support disease mechanisms that involve the activity
of immunity-related pathways in the brain.
Key Words
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Article info
Publication history
Published online: March 25, 2011
Accepted:
January 28,
2011
Received in revised form:
December 30,
2010
Received:
November 16,
2010
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
