Strong association of de novo copy number mutations with sporadic schizophrenia.
paper
Cited
Public
Unavailable
- Authors
- Xu, Bin; Roos, J Louw; Levy, Shawn; van Rensburg, E J; Gogos, Joseph A; Karayiorgou, Maria
- Year
- 2008
- Journal
- Nature genetics
- PMID
- 18511947
- DOI
- 10.1038/ng.162
Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms. Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming CN mutations. Confirmed de novo mutations were significantly associated with schizophrenia (P = 0.00078) and were collectively approximately 8 times more frequent in sporadic (but not familial) cases with schizophrenia than in unaffected controls. In comparison, rare inherited CN mutations were only modestly enriched in sporadic cases. Our results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease.
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| Contribution of global rare copy-number variants to the risk of sporadic congenital heart disease. | Soemedi R et al. | β | 2012 | β |
| Current understanding of human genetics and genetic analysis of psoriasis. | Oka A et al. | β | 2012 | β |
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| Diverse types of genetic variation converge on functional gene networks involved in schizophrenia. | Gilman SR et al. | β | 2012 | β |
| Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways. | Griswold AJ et al. | β | 2012 | β |
| Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses. | Visscher PM et al. | β | 2012 | β |
| Genetic and cognitive windows into circuit mechanisms of psychiatric disease. | Arguello PA et al. | β | 2012 | β |
| Genetic architectures of psychiatric disorders: the emerging picture and its implications. | Sullivan PF et al. | β | 2012 | β |
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| Genome wide association studies (GWAS) and copy number variation (CNV) studies of the major psychoses: what have we learnt? | Lee KW et al. | β | 2012 | β |
| Genome-wide association study of copy number variants suggests LTBP1 and FGD4 are important for alcohol drinking. | Pei YF et al. | β | 2012 | β |
| Genomic structural variation in psychiatric disorders. | Rucker JJ et al. | β | 2012 | β |
| Human genetics of schizophrenia. | Claes S et al. | β | 2012 | β |
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| Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders. | Van Den Bossche MJ et al. | β | 2012 | β |
| Identification of genome-wide copy number variations among diverse pig breeds by array CGH. | Li Y et al. | β | 2012 | β |
| Implications of gene copy-number variation in health and diseases. | Almal SH et al. | β | 2012 | β |
| Imprinted DLK1-DIO3 region of 14q32 defines a schizophrenia-associated miRNA signature in peripheral blood mononuclear cells. | Gardiner E et al. | β | 2012 | β |
| Independent estimation of the frequency of rare CNVs in the UK population confirms their role in schizophrenia. | Grozeva D et al. | β | 2012 | β |
| Inheritance model introduces differential bias in CNV calls between parents and offspring. | Kim S et al. | β | 2012 | β |
| Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression. | Morgan VA et al. | β | 2012 | β |
| Involvement of PTPN5, the gene encoding the striatal-enriched protein tyrosine phosphatase, in schizophrenia and cognition. | Pelov I et al. | β | 2012 | β |
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| Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. | Goriely A et al. | β | 2012 | β |
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| Rare copy number variants in tourette syndrome disrupt genes in histaminergic pathways and overlap with autism. | Fernandez TV et al. | β | 2012 | β |
| Rare de novo germline copy-number variation in testicular cancer. | Stadler ZK et al. | β | 2012 | β |
| Rare genomic deletions and duplications and their role in neurodevelopmental disorders. | Glessner JT et al. | β | 2012 | β |
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| RBFOX1 regulates both splicing and transcriptional networks in human neuronal development. | Fogel BL et al. | β | 2012 | β |
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| The interleukin 3 gene (IL3) contributes to human brain volume variation by regulating proliferation and survival of neural progenitors. | Luo XJ et al. | β | 2012 | β |
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| What is complex about complex disorders? | Mitchell KJ | β | 2012 | β |
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| A comparison of genomic copy number calls by Partek Genomics Suite, Genotyping Console and Birdsuite algorithms to quantitative PCR. | Grayson BL et al. | β | 2011 | β |
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| Analysis of copy number variants in the cattle genome. | Kijas JW et al. | β | 2011 | β |
| Analysis of neurogranin (NRGN) in schizophrenia. | Smith RL et al. | β | 2011 | β |
| An optimal weighted aggregated association test for identification of rare variants involved in common diseases. | Sul JH et al. | β | 2011 | β |
| A population genetic approach to mapping neurological disorder genes using deep resequencing. | Myers RA et al. | β | 2011 | β |
| Array-based MLPA to detect recurrent copy number variations in patients with idiopathic mental retardation. | Rooms L et al. | β | 2011 | β |
| Assessment of copy number variation using the Illumina Infinium 1M SNP-array: a comparison of methodological approaches in the Spanish Bladder Cancer/EPICURO study. | Marenne G et al. | β | 2011 | β |
| A systematic review and meta-analysis of the fertility of patients with schizophrenia and their unaffected relatives. | Bundy H et al. | β | 2011 | β |
| Candidate genes for idiopathic epilepsy in four dog breeds. | Ekenstedt KJ et al. | β | 2011 | β |
| Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders. | Mikhail FM et al. | β | 2011 | β |
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| Comprehensive analysis of the genes responsible for neuroacanthocytosis in mood disorder and schizophrenia. | Shimo H et al. | β | 2011 | β |
| Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants. | Pinto D et al. | β | 2011 | β |
| Copy number variants for schizophrenia and related psychotic disorders in Oceanic Palau: risk and transmission in extended pedigrees. | Melhem N et al. | β | 2011 | β |
| Copy number variations and primary open-angle glaucoma. | Davis LK et al. | β | 2011 | β |
| Copy number variations of chromosome 16p13.1 region associated with schizophrenia. | Ingason A et al. | β | 2011 | β |
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| Determination of beta-defensin genomic copy number in different populations: a comparison of three methods. | Fode P et al. | β | 2011 | β |
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| Developments in schizophrenia genetics: from linkage to microchips, deletions and duplications. | Haraldsson HM et al. | β | 2011 | β |
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| Drosophila duplication hotspots are associated with late-replicating regions of the genome. | Cardoso-Moreira M et al. | β | 2011 | β |
| Evidence for altered hippocampal function in a mouse model of the human 22q11.2 microdeletion. | Drew LJ et al. | β | 2011 | β |
| Exome sequencing supports a de novo mutational paradigm for schizophrenia. | Xu B et al. | β | 2011 | β |
| Expanding the range of ZNF804A variants conferring risk of psychosis. | Steinberg S et al. | β | 2011 | β |
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| Genetic contributions to behavioural diversity at the gene-environment interface. | Bendesky A et al. | β | 2011 | β |
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| Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research. | Hochstenbach R et al. | β | 2011 | β |
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| Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. | Lesch KP et al. | β | 2011 | β |
| Genome-wide investigation of rare structural variants identifies VIPR2 as a new candidate gene for schizophrenia. | Nieratschker V et al. | β | 2011 | β |
| High frequencies of de novo CNVs in bipolar disorder and schizophrenia. | Malhotra D et al. | β | 2011 | β |
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| Inherited balanced translocation t(9;17)(q33.2;q25.3) concomitant with a 16p13.1 duplication in a patient with schizophrenia. | Fullston T et al. | β | 2011 | β |
| Microdeletions and microduplications in patients with congenital heart disease and multiple congenital anomalies. | Goldmuntz E et al. | β | 2011 | β |
| Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. | Sanders SJ et al. | β | 2011 | β |
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| RA-GEF-1 (Rapgef2) is essential for proper development of the midline commissures. | Bilasy SE et al. | β | 2011 | β |
| Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD. | Lionel AC et al. | β | 2011 | β |
| Rare de novo and transmitted copy-number variation in autistic spectrum disorders. | Levy D et al. | β | 2011 | β |
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| Synthetic associations created by rare variants do not explain most GWAS results. | Wray NR et al. | β | 2011 | β |
| The 22q11.2 microdeletion: fifteen years of insights into the genetic and neural complexity of psychiatric disorders. | Drew LJ et al. | β | 2011 | β |
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| 22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. | Karayiorgou M et al. | β | 2010 | β |
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