Penetrance for copy number variants associated with schizophrenia. 2010

Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
Institute of Psychiatry, MRC SGDP Centre, King's College London, London, UK. evangelos.vassos@iop.kcl.ac.uk

The discovery of 'high-risk' de novo copy number variants (CNVs) associated with neuropsychiatric disorders such as schizophrenia offers the opportunity to translate these findings into useful tools for clinical geneticists. However, this will require estimation of penetrance for these variants, which has not yet been properly considered. To facilitate this process, we estimated the penetrance of CNVs associated with schizophrenia, at 15q13.3, 1q21.1, 15q11.2, 17p12, 2p16.3, 16p13.1 and 16p11.2 with a novel Bayesian method applied to pooled data from published case-control studies. For these CNVs, penetrance for schizophrenia was between 2 and 7.4%, which contrasts with the much higher penetrance for schizophrenia of the 22q11.2 deletions found in velo-cardio-facial syndrome. The highest penetrance was for 15q13.3 deletion (6-9% in individual studies) and the lowest was for 15q11.2 (2%). CNVs confer much higher risk for schizophrenia than common variants, but their penetrance is substantially lower than Mendelian disorders or other syndromic conditions. Since these CNVs predispose to multiple disorders, including epilepsy, autism and intellectual impairment, penetrance estimates will also need to take into account diagnostic specificity, and their overall penetrance for any neuropsychiatric disorder is likely to be much higher. Thus, although CNVs are still far from being clinically useful or relevant to genetic counselling for specific disorders, their detection may hold an important clinical value in predicting negative developmental outcomes.

UI MeSH Term Description Entries
D002872 Chromosome Deletion Actual loss of portion of a chromosome. Monosomy, Partial,Partial Monosomy,Deletion, Chromosome,Deletions, Chromosome,Monosomies, Partial,Partial Monosomies
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012559 Schizophrenia A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior. Dementia Praecox,Schizophrenic Disorders,Disorder, Schizophrenic,Disorders, Schizophrenic,Schizophrenias,Schizophrenic Disorder
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D056915 DNA Copy Number Variations Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease. Copy Number Polymorphism,DNA Copy Number Variant,Copy Number Changes, DNA,Copy Number Polymorphisms,Copy Number Variants, DNA,Copy Number Variation, DNA,DNA Copy Number Change,DNA Copy Number Changes,DNA Copy Number Polymorphism,DNA Copy Number Polymorphisms,DNA Copy Number Variants,DNA Copy Number Variation,Polymorphism, Copy Number,Polymorphisms, Copy Number
D018628 Gene Dosage The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage. Gene Copy Number,Copy Number, Gene,Copy Numbers, Gene,Dosage, Gene,Dosages, Gene,Gene Copy Numbers,Gene Dosages,Number, Gene Copy,Numbers, Gene Copy

Related Publications

Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
July 2021, Biological psychiatry,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
March 2014, Biological psychiatry,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
January 2013, PloS one,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
February 2017, Molecular psychiatry,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
December 2011, Biological psychiatry,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
April 2020, Disease models & mechanisms,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
September 2016, JAMA psychiatry,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
March 2023, Clinical genetics,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
January 2014, PloS one,
Evangelos Vassos, and David A Collier, and Simon Holden, and Christine Patch, and Dan Rujescu, and David St Clair, and Cathryn M Lewis
June 2016, Pediatric research,
Copied contents to your clipboard!