Priority CommunicationThe Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia
Section snippets
Patient Samples
The German case–control discovery sample consisted of patients with schizophrenia recruited from consecutive admissions to the inpatient units of the Central Institute of Mental Health in Mannheim, and the Department of Psychiatry at the University of Bonn. A description of this sample is given elsewhere (M.R., M.M., et al., unpublished data) (23). In brief, the sample includes genotypes from 466 patients and 1273 controls. Diagnoses were made according to DSM-IV criteria based on an Structured
Phase I: Mining of German Case–Control GWAS Data
Candidate genes were selected on the basis of our Gene Set Enrichment analysis of rat hippocampal HFS-LTP (17), as described in Methods and Materials. A knowledge-based selection was performed for genes that encode 1) complement-regulatory proteins acting from the step of initiation of the classical complement cascade (the C1Q complex) to the activation of C3, and 2) key regulators of antigen loading and presentation by MHC class I and MHC class II genes (Table S1 in Supplement 1). We examined
Discussion
Among the human RCAs that we selected for genetic association tests, the two homologous genes encoding the multiple domain proteins CSMD1 (chr. 8p23.2) and CSMD2 (chr. 1p35.1-34.3) are strongly associated with schizophrenia, suggesting that variants of RCAs have a significant effect on disease susceptibility. Notably, our candidate gene approach on a small number of markers resulted in genetic associations that in comparison with genome-wide analysis reaches the commonly accepted genome-wide
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