Copy number variants in German patients with schizophrenia

PLoS One. 2013 Jul 2;8(7):e64035. doi: 10.1371/journal.pone.0064035. Print 2013.

Abstract

Large rare copy number variants (CNVs) have been recognized as significant genetic risk factors for the development of schizophrenia (SCZ). However, due to their low frequency (1∶150 to 1∶1000) among patients, large sample sizes are needed to detect an association between specific CNVs and SCZ. So far, the majority of genome-wide CNV analyses have focused on reporting only CNVs that reached a significant P-value within the study cohort and merely confirmed the frequency of already-established risk-carrying CNVs. As a result, CNVs with a very low frequency that might be relevant for SCZ susceptibility are lost for secondary analyses. In this study, we provide a concise collection of high-quality CNVs in a large German sample consisting of 1,637 patients with SCZ or schizoaffective disorder and 1,627 controls. All individuals were genotyped on Illumina's BeadChips and putative CNVs were identified using QuantiSNP and PennCNV. Only those CNVs that were detected by both programs and spanned ≥30 consecutive SNPs were included in the data collection and downstream analyses (2,366 CNVs, 0.73 CNVs per individual). The genome-wide analysis did not reveal a specific association between a previously unknown CNV and SCZ. However, the group of CNVs previously reported to be associated with SCZ was more frequent in our patients than in the controls. The publication of our dataset will serve as a unique, easily accessible, high-quality CNV data collection for other research groups. The dataset could be useful for the identification of new disease-relevant CNVs that are currently overlooked due to their very low frequency and lack of power for their detection in individual studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • DNA Copy Number Variations*
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotyping Techniques / statistics & numerical data*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / ethnology
  • Psychotic Disorders / genetics*
  • Risk Factors
  • Schizophrenia / diagnosis
  • Schizophrenia / ethnology
  • Schizophrenia / genetics*
  • White People

Grants and funding

This study was supported by the German Federal Ministry of Education and Research, within the context of: the National Genome Research Network 2; the National Genome Research Network plus; and the Integrated Genome Research Network (IG) MooDS (grant 01GS08144 to SC and MMN, grant 01GS08147 to MR). Additionally, this work was supported by the European Union grant number HEALTH-F4-2009-242257 (Project ADAMS). MMN also received support from the Alfried Krupp von Bohlen und Halbach-Stiftung. The HNR cohort was established with the support of the Heinz Nixdorf Foundation. IN was supported by a Junior Scientist grant of the Interdiziplinäres Zentrum für Klinische Forschung Jena. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.