The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia
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The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia. / Håvik, Bjarte; Le Hellard, Stephanie; Rietschel, Marcella; Lybæk, Helle; Djurovic, Srdjan; Mattheisen, Manuel; Mühleisen, Thomas W; Degenhardt, Franziska; Priebe, Lutz; Maier, Wolfgang; Breuer, Rene; Schulze, Thomas G; Agartz, Ingrid; Melle, Ingrid; Hansen, Thomas; Bramham, Clive R; Nöthen, Markus M; Stevens, Beth; Werge, Thomas; Andreassen, Ole A; Cichon, Sven; Steen, Vidar M.
I: Biological Psychiatry, Bind 70, Nr. 1, 2011, s. 35-42.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia
AU - Håvik, Bjarte
AU - Le Hellard, Stephanie
AU - Rietschel, Marcella
AU - Lybæk, Helle
AU - Djurovic, Srdjan
AU - Mattheisen, Manuel
AU - Mühleisen, Thomas W
AU - Degenhardt, Franziska
AU - Priebe, Lutz
AU - Maier, Wolfgang
AU - Breuer, Rene
AU - Schulze, Thomas G
AU - Agartz, Ingrid
AU - Melle, Ingrid
AU - Hansen, Thomas
AU - Bramham, Clive R
AU - Nöthen, Markus M
AU - Stevens, Beth
AU - Werge, Thomas
AU - Andreassen, Ole A
AU - Cichon, Sven
AU - Steen, Vidar M
N1 - Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
U2 - 10.1016/j.biopsych.2011.01.030
DO - 10.1016/j.biopsych.2011.01.030
M3 - Journal article
C2 - 21439553
VL - 70
SP - 35
EP - 42
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 1
ER -
ID: 34053366