The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia
2011 | journal article. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia
Havik, B.; Le Hellard, S.; Rietschel, M.; Lybaek, H.; Djurovic, S.; Mattheisen, M. & Muehleisen, T. W. et al. (2011)
Biological Psychiatry, 70(1) pp. 35-42. DOI: https://doi.org/10.1016/j.biopsych.2011.01.030
Documents & Media
Details
- Authors
- Havik, Bjarte; Le Hellard, Stephanie; Rietschel, Marcella; Lybaek, Helle; Djurovic, Srdjan; Mattheisen, Manuel; Muehleisen, Thomas W.; Degenhardt, Franziska A.; Priebe, Lutz; Maier, Wolfgang; Breuer, Rene; Schulze, Thomas G.; Agartz, Ingrid; Melle, Ingrid; Hansen, Thomas C.; Bramham, Clive R.; Noethen, Markus M.; Stevens, Beth; Werge, Thomas; Andreassen, Ole A.; Cichon, Sven; Steen, Vidar M.
- Abstract
- 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 x 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.
- Issue Date
- 2011
- Status
- published
- Publisher
- Elsevier Science Inc
- Journal
- Biological Psychiatry
- ISSN
- 0006-3223