The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia
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 × 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…
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Recent data from genome-wide association studies and analyses of postmortem human brain tissue have suggested that microglia and/or the complement cascade may also be involved in the development and pathogenesis of neurodevelopmental and psychiatric disorders.
“In addition to diseases associated with neurodegeneration, recent data from genome-wide association studies and analyses of postmortem human brain tissue have suggested that microglia and/or the complement cascade may also be involved in the development and pathogenesis of neurodevelopmental and psychiatric disorders (e.g., autism, obsessive compulsive disorder, schizophrenia, etc.) (Chen et al.,”
From Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner (2012) · cites this paper as Havik et al., 2011
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- Authors
- Håvik, B., Le Hellard, S., Rietschel, M., Lybæk, H., Djurovic, S., Mattheisen, M., Mühleisen, T. W., Degenhardt, F., Priebe, L., Maier, W., Breuer, R., Schulze, T. G., Agartz, I., Melle, I., Hansen, T., Bramham, C. R., Nöthen, M. M., Stevens, B., Werge, T., Andreassen, O. A., Cichon, S., & Steen, V. M.
- Affiliations
- Haukeland University Hospital (NO)
- Heidelberg University (DE)
- University of Oslo (NO)
- University of Bonn (DE)
- Oslo University Hospital (NO)
- Copenhagen University Hospital (DK)
- University of Bergen (NO)
- Boston Children's Hospital (US)
- Corresponding author
- Håvik, Bjarte
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 70
- Issue
- 1
- Pages
- 35-42
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1974103256
- Cited by
- 168
- References
- 7
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 13 · 2021: 10 · 2020: 15 · 2019: 10 · 2018: 8 · 2017: 16 · 2016: 13 · 2015: 18 · 2014: 13 · 2013: 9 · 2012: 14
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- GRO (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Helse Vest Regionalt Helseføretak
- Alfried Krupp von Bohlen und Halbach-Stiftung
- Universitetet i Oslo
- Norges Forskningsråd
- Münchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität München (163070/V50, 167153/V50)
- Bundesministerium für Bildung und Forschung (01GS08144, 01GS08147)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- schizophrenia, complement system, CSMD1, CD46, HLA-DMB, genetic susceptibility, single nucleotide polymorphisms, immune pathways, learning and memory, long-term potentiation, hippocampus, major histocompatibility complex
- MeSH terms
- Adult, Complement System Proteins, Female, Genotype, Humans, Major Histocompatibility Complex, Male, Membrane Proteins, Schizophrenia, Case-Control Studies, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins, Genetic Association Studies
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