Recurrent CNVs Disrupt Three Candidate Genes in Schizophrenia Patients

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2008 Oct 23

PMID 18940311

Citations 138

Authors

Terry Vrijenhoek

Jacobine E Buizer-Voskamp

Inge van der Stelt

Eric Strengman

Chiara Sabatti

Ad Geurts van Kessel

Han G Brunner

Roel A Ophoff

Joris A Veltman

Affiliations

Soon will be listed here.

Abstract

Schizophrenia is a severe psychiatric disease with complex etiology, affecting approximately 1% of the general population. Most genetics studies so far have focused on disease association with common genetic variation, such as single-nucleotide polymorphisms (SNPs), but it has recently become apparent that large-scale genomic copy-number variants (CNVs) are involved in disease development as well. To assess the role of rare CNVs in schizophrenia, we screened 54 patients with deficit schizophrenia using Affymetrix's GeneChip 250K SNP arrays. We identified 90 CNVs in total, 77 of which have been reported previously in unaffected control cohorts. Among the genes disrupted by the remaining rare CNVs are MYT1L, CTNND2, NRXN1, and ASTN2, genes that play an important role in neuronal functioning but--except for NRXN1--have not been associated with schizophrenia before. We studied the occurrence of CNVs at these four loci in an additional cohort of 752 patients and 706 normal controls from The Netherlands. We identified eight additional CNVs, of which the four that affect coding sequences were found only in the patient cohort. Our study supports a role for rare CNVs in schizophrenia susceptibility and identifies at least three candidate genes for this complex disorder.

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