Dataset Information

Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients.

ABSTRACT: Since 2008, multiple studies have reported on copy number variations (CNVs) in schizophrenia. However, many regions are unique events with minimal overlap between studies. This makes it difficult to gain a comprehensive overview of all CNVs involved in the etiology of schizophrenia. We performed a systematic CNV study on the basis of a homogeneous genome-wide dataset aiming at all CNVs ? 50 kilobase pair. We complemented this analysis with a review of cytogenetic and chromosomal abnormalities for schizophrenia reported in the literature with the purpose of combining classical genetic findings and our current understanding of genomic variation.We investigated 834 Dutch schizophrenia patients and 672 Dutch control subjects. The CNVs were included if they were detected by QuantiSNP (http://www.well.ox.ac.uk/QuantiSNP/) as well as PennCNV (http://www.neurogenome.org/cnv/penncnv/) and contain known protein coding genes. The integrated identification of CNV regions and cytogenetic loci indicates regions of interest (cytogenetic regions of interest [CROIs]).In total, 2437 CNVs were identified with an average number of 2.1 CNVs/subject for both cases and control subjects. We observed significantly more deletions but not duplications in schizophrenia cases versus control subjects. The CNVs identified coincide with loci previously reported in the literature, confirming well-established schizophrenia CROIs 1q42 and 22q11.2 as well as indicating a potentially novel CROI on chromosome 5q35.1.Chromosomal deletions are more prevalent in schizophrenia patients than in healthy subjects and therefore confer a risk factor for pathogenicity. The combination of our CNV data with previously reported cytogenetic abnormalities in schizophrenia provides an overview of potentially interesting regions for positional candidate genes.

SUBMITTER: Buizer-Voskamp JE

PROVIDER: S-EPMC3137747 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients.

Buizer-Voskamp Jacobine E JE Muntjewerff Jan-Willem JW Strengman Eric E Sabatti Chiara C Stefansson Hreinn H Vorstman Jacob A S JA Ophoff Roel A RA

Biological psychiatry 20110413 7

<h4>Background</h4>Since 2008, multiple studies have reported on copy number variations (CNVs) in schizophrenia. However, many regions are unique events with minimal overlap between studies. This makes it difficult to gain a comprehensive overview of all CNVs involved in the etiology of schizophrenia. We performed a systematic CNV study on the basis of a homogeneous genome-wide dataset aiming at all CNVs ≥ 50 kilobase pair. We complemented this analysis with a review of cytogenetic and chromosom ...[more]

PMID: 21489405

Similar Datasets

Project description:BackgroundFasting glucose and fasting insulin are glycemic traits closely related to diabetes, and understanding the role of genetic factors in these traits can help reveal the etiology of type 2 diabetes. Although single nucleotide polymorphisms (SNPs) in several candidate genes have been found to be associated with fasting glucose and fasting insulin, copy number variations (CNVs), which have been reported to be associated with several complex traits, have not been reported for association with these two traits. We aimed to identify CNVs associated with fasting glucose and fasting insulin.ResultsWe conducted a genome-wide CNV association analysis for fasting plasma glucose (FPG) and fasting plasma insulin (FPI) using a family-based genome-wide association study sample from a Han Chinese population in Taiwan. A family-based CNV association test was developed in this study to identify common CNVs (i.e., CNVs with frequencies ≥ 5%), and a generalized estimating equation approach was used to test the associations between the traits and counts of global rare CNVs (i.e., CNVs with frequencies <5%). We found a significant genome-wide association for common deletions with a frequency of 5.2% in the Scm-like with four mbt domains 1 (SFMBT1) gene with FPG (association p-value = 2×10-4 and an adjusted p-value = 0.0478 for multiple testing). No significant association was observed between global rare CNVs and FPG or FPI. The deletions in 20 individuals with DNA samples available were successfully validated using PCR-based amplification. The association of the deletions in SFMBT1 with FPG was further evaluated using an independent population-based replication sample obtained from the Taiwan Biobank. An association p-value of 0.065, which was close to the significance level of 0.05, for FPG was obtained by testing 9 individuals with CNVs in the SFMBT1 gene region and 11,692 individuals with normal copies in the replication cohort.ConclusionsPrevious studies have found that SNPs in SFMBT1 are associated with blood pressure and serum urate concentration, suggesting that SFMBT1 may have functional implications in some metabolic-related traits.

Dataset Information

Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients.

Publications

Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets