Recurrent CNVs disrupt three candidate genes in schizophrenia patients |
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Authors: | Vrijenhoek Terry Buizer-Voskamp Jacobine E van der Stelt Inge Strengman Eric;Genetic Risk and Outcome in Psychosis Consortium Sabatti Chiara Geurts van Kessel Ad Brunner Han G Ophoff Roel A Veltman Joris A |
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Institution: | 1 Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands 2 Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre 3584 CX Utrecht, Utrecht, The Netherlands 3 Complex Genetics Section, Division of Biomedical Genetics, Department of Medical Genetics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands 4 Departments of Human Genetics and Statistics, University of California Los Angeles, Los Angeles, CA 90095, USA 5 Center for Neurobehavioral Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA |
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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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