Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.
Open accessAbstract
We report the results of two studies examining the genetic overlap between schizophrenia and velocardiofacial syndrome. In study A, we characterize two interstitial deletions identified on chromosome 22q11 in a sample of schizophrenic patients. The size of the deletions was estimated to be between 1.5 and 2 megabases. In study B, we examine whether variations in deletion size are associated with the schizophrenic phenotype in velocardiofacial syndrome patients. Our results show that a region of the genome that has been previously implicated by genetic linkage analysis can harbor genetic lesions that increase the susceptibility to schizophrenia. Our findings should facilitate identification and cloning of the schizophrenia susceptibility gene(s) in this region and identification of more homogeneous subgroups of patients.
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A large 3 Mb deletion at chromosome 22q11.21 has long been known as a significant risk factor for schizophrenia.
“In schizophrenia, a large (3Mb) deletion at chromosome 22q11.21 has long been known as a significant risk factor for schizophrenia (Karayiorgou et al., 1995).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Karayiorgou et al., 1995
Df(16)A +/- mice are a model of DiGeorge syndrome, caused by a microdeletion (22q11.2) that accounts for a small percentage of schizophrenia cases.
“For example, Df(16)A +/-mice are a model of DiGeorge syndrome, caused by a microdeletion (22q11.2) that accounts for a small percentage of schizophrenia cases 74 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [74]
Several rare recurrent copy number variants (CNVs) have been robustly associated with schizophrenia, as exemplified by dramatically higher rates of schizophrenia in 22q11.2 deletion carriers.
“Several rare (MAF < 0.1%) recurrent copy number variants (CNVs) have also been robustly associated with schizophrenia, as exemplified by the dramatically higher rates of schizophrenia in 22q11.2deletion carriers 7,12 .”
From Exome sequencing identifies rare coding variants in 10 genes which confer substantial risk for schizophrenia (2020) · cites this paper as [12]
Common variants explain about 24% of variance in schizophrenia liability.
“As a class of variation, common variants explain ~24% of the variance in disease liability14.”
From Rare coding variants in ten genes confer substantial risk for schizophrenia (2022) · cites this paper as [14]
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- Authors
- Karayiorgou, M., Morris, M. A., Morrow, B., Shprintzen, R. J., Goldberg, R., Borrow, J., Gos, A., Nestadt, G., Wolyniec, P. S., & Lasseter, V. K.
- Affiliations
- Fred Hutch Cancer Center (US)
- University of Geneva (CH)
- Yeshiva University (US)
- Johns Hopkins University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-08-15
- Volume
- 92
- Issue
- 17
- Pages
- 7612-7616
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC41195
- OpenAlex
- W1996124672
- Cited by
- 628
- References
- 0
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 16 · 2022: 9 · 2021: 4 · 2020: 7 · 2019: 19 · 2018: 10 · 2017: 16 · 2016: 21 · 2015: 28 · 2014: 29 · 2013: 37 · 2012: 27
- FWCI
- 11.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh045588-04)
- National Institute of Mental Health (MH45588)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- schizophrenia, 22q11.2 deletion syndrome, chromosome 22q11, interstitial deletion, genetic susceptibility, deletion size, genetic linkage, schizophrenia risk genes, genetic heterogeneity
- MeSH terms
- Abnormalities, Multiple, Adolescent, Adult, Cell Line, Transformed, Chromosome Deletion, Chromosome Mapping, Chromosomes, Human, Pair 22, Herpesvirus 4, Human, Female, Genetic Markers, Humans, Lymphocytes, Male, Schizophrenia, Syndrome, Incidence, Polymerase Chain Reaction, In Situ Hybridization, Fluorescence, DNA Primers, Genetic Predisposition to Disease
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