The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems
Open accessAbstract
Purpose : Recently, molecular cytogenetic techniques have identified novel copy number variants in individuals with schizophrenia. However, no large-scale prospective studies have been performed to characterize the broader spectrum of phenotypes associated with such copy number variants in individuals with unexplained physical and intellectual disabilities encountered in a diagnostic setting.Methods : We analyzed 38,779 individuals referred to our diagnostic laboratory for microarray testing for the presence of copy number variants encompassing 20 putative schizophrenia susceptibility loci. We also analyzed the indications for study for individuals with copy number variants overlapping those found in six individuals referred for schizophrenia.Results : After excluding larger gains or losses that encompassed additional genes outside the candidate loci (e.g., whole-arm gains/losses), we identified 1113 individuals with copy number variants encompassing schizophrenia susceptibility loci and 37 individuals with copy number variants overlapping those present in the six individuals referred to our laboratory for schizophrenia. Of these, 1035 had a copy number variant of one of six recurrent loci: 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11, and 22q11.2. The indications for study for these 1150 individuals were diverse and included developmental delay, intellectual disability, autism spectrum, and multiple congenital anomalies.Conclusion : The results from our study, the largest genotype-first analysis of schizophrenia susceptibility loci to date, suggest that the phenotypic effects of copy number variants associated with schizophrenia are pleiotropic and imply the existence of shared biologic pathways among multiple neurodevelopmental conditions.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Data compiled from eight studies [13, 15–17, 20, 24, 26, 33] screening individuals with either ASD, ID, developmental delay (DD), dysmorphic features (DF), multiple congenital anomalies (MCA), obesity, or seizures find 16p11.2 deletions at rates of 0.25–2.9%, and duplications at rates between 0.15–0.78% (Table 1).”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [26]
In the citing paper
“Schizophrenia (SZ) appears to be associated more strongly with 16p11.2 duplications [9, 25–27].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [26]
In the citing paper
“Developmental delays and craniofacial anomalies associated with a loss of genetic material at the NRG3 locus, accompanied by a gain of material at the DLGAP1 site, have also been reported [97]”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [97]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A. S., Zackai, E. H., Emanuel, B. S., Vermeesch, J. R., Morrow, B. E., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.71 · Cited by 2,236
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800
Large recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745
Common variants conferring risk of schizophrenia
†Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., Pietiläinen, O. P. H., Mors, O., et al. (2009) · Nature · doi:10.1038/nature08186 · Cited by 1,677
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475
Disruption of two novel genes by a translocation co-segregating with schizophrenia
Millar, J. K. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.9.1415 · Cited by 1,254
Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia
Lewis, C. M., Levinson, D. F., Wise, L. H., DeLisi, L. E., Straub, R. E., Hovatta, I., Williams, N. M., Schwab, S. G., Pulver, A. E., Faraone, S. V., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/376549 · Cited by 1,134
High rates of schizophrenia in adults with velo-cardio-facial syndrome
Murphy, K. C., Jones, L. A., & Owen, M. J. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.10.940 · Cited by 1,024
Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes
Mefford, H. C., Sharp, A. J., Baker, C., Itsara, A., Jiang, Z., Buysse, K., Huang, S., Maloney, V. K., Crolla, J. A., Baralle, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0805384 · Cited by 804
Blackwood, D., Fordyce, A., Walker, M. T., Clair, D. M. S., Porteous, D. J., & Muir, W. J. (2001) · The American Journal of Human Genetics · doi:10.1086/321969 · Cited by 734
Association within a family of a balanced autosomal translocation with major mental illness
St Clair, D., Blackwood, D., Muir, W., Walker, M., St Clair, D., Muir, W., Carothers, A., Spowart, G., Gosden, C., & Evans, H. J. (1990) · The Lancet · doi:10.1016/0140-6736(90)91520-k · Cited by 727
Microduplications of 16p11.2 are associated with schizophrenia
Wellcome Trust Case Control Consortium, McCarthy, S. E., Makarov, V., Kirov, G., Addington, A. M., McClellan, J., Yoon, S., Perkins, D. O., Dickel, D. E., Kusenda, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.474 · Cited by 711
A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Girirajan, S., Rosenfeld, J. A., Cooper, G. M., Antonacci, F., Siswara, P., Itsara, A., Vives, L., Walsh, T., McCarthy, S. E., Baker, C., et al. (2010) · Nature Genetics · doi:10.1038/ng.534 · Cited by 667
Self-citationCopy-number variations associated with neuropsychiatric conditions
Cook Jr, E. H., & Scherer, S. W. (2008) · Nature · doi:10.1038/nature07458 · Cited by 659
Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11.
Karayiorgou, M., Morris, M. A., Morrow, B., Shprintzen, R. J., Goldberg, R., Borrow, J., Gos, A., Nestadt, G., Wolyniec, P. S., & Lasseter, V. K. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7612 · Cited by 628
Population analysis of large copy number variants and hotspots of human genetic disease
Itsara, A., Cooper, G. M., Baker, C., Girirajan, S., Li, J., Absher, D., Krauss, R. M., Myers, R. M., Ridker, P. M., Chasman, D. I., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.12.014 · Cited by 591
Psychiatric genetics: progress amid controversy
Burmeister, M., McInnis, M. G., & Zöllner, S. K. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2381 · Cited by 541
Disruption of the neurexin 1 gene is associated with schizophrenia
Rujescu, D., Ingason, A., Cichon, S., Pietiläinen, O. P. H., Barnes, M. R., Toulopoulou, T., Picchioni, M., Vassos, E., Ettinger, U., Bramon, E., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddn351 · Cited by 471
A Genome-Wide Investigation of SNPs and CNVs in Schizophrenia
Need, A. C., Ge, D., Weale, M. E., Maia, J. M., Feng, S., Heinzen, E. L., Shianna, K. V., Yoon, W., Kasperavičiūtė, D., Gennarelli, M., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000373 · Cited by 454
Detection of sharing by descent, long-range phasing and haplotype imputation
Kong, A., Masson, G., Frigge, M. L., Gylfason, A., Zusmanovich, P., Thorleifsson, G., Olason, P. I., Ingason, A., Steinberg, S., Rafnar, T., et al. (2008) · Nature Genetics · doi:10.1038/ng.216 · Cited by 447
Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies
de Kovel, C. G. F., Trucks, H., Helbig, I., Mefford, H. C., Baker, C., Leu, C., Kluck, C., Muhle, H., von Spiczak, S., Ostertag, P., et al. (2010) · Brain · doi:10.1093/brain/awp262 · Cited by 445
Support for the involvement of large copy number variants in the pathogenesis of schizophrenia.
Kirov, G., Grozeva, D., Norton, N., Ivanov, D., Mantripragada, K. K., Holmans, P., International Schizophrenia Consortium, the Wellcome Trust Case Control Consortium, Craddock, N., Owen, M. J., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp043 · Cited by 390
Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia
Kirov, G., Gumus, D., Chen, W., Norton, N., Georgieva, L., Sari, M., O'Donovan, M. C., Erdogan, F., Owen, M. J., Ropers, H.-H., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm323 · Cited by 377
Moskvina, V, Craddock, N., Holmans, P., Nikolov, I., Pahwa, J. S., Green, E., Wellcome Trust Case Control Consortium, Owen, M. J., & O'Donovan, M. C. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.133 · Cited by 363
Symptoms, signs, and diagnosis of schizophrenia
Andreasen, N. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91325-4 · Cited by 357
Genomewide association for schizophrenia in the CATIE study: results of stage 1
Sullivan, P. F., Lin, D. Y., Tzeng, J., van den Oord, E. J. C. G., Perkins, D. O., Stroup, T. S., Wagner, M. J., Lee, S., Wright, F. A., Zou, F., et al. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.25 · Cited by 357
Sullivan, P. F. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020212 · Cited by 333
CNTNAP2 gene dosage variation is associated with schizophrenia and epilepsy
Friedman, J. I., Vrijenhoek, T., Markx, S., Janssen, I. M., van der Vliet, W. A., Faas, B. H. W., Knoers, N. V. A. M., Cahn, W., Kahn, R. S., Edelmann, L. J., et al. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002049 · Cited by 297
Ballif, B. C., Theisen, A. P., Coppinger, J., Gowans, G. C., Hersh, J. H., Madan‐Khetarpal, S., Schmidt, K. R., Tervo, R. C., Escobar, L., Friedrich, C. A., et al. (2008) · Molecular Cytogenetics · doi:10.1186/1755-8166-1-8 · Cited by 296
Self-citationSchizophrenia: a common disease caused by multiple rare alleles
McClellan, J. M., Susser, E., & King, M.-C. (2007) · British Journal of Psychiatry · doi:10.1192/bjp.bp.106.025585 · Cited by 296
Meta-analysis of 32 genome-wide linkage studies of schizophrenia
Ng, M., Levinson, D. F., Faraone, S. V., Suarez, B. K., DeLisi, L. E., Arinami, T., Riley, B. P., Paunio, T., Pulver, A. E., Irmansyah, et al. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.135 · Cited by 283
Copy number variations of chromosome 16p13.1 region associated with schizophrenia
Ingason, A., Rujescu, D., Cichon, S., Sigurdsson, E., Sigmundsson, T., Pietiläinen, O. P. H., Buizer-Voskamp, J. E., Strengman, E., Francks, C., Muglia, P., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2009.101 · Cited by 258
Elsea, S. H., & Girirajan, S. (2008) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5202009 · Cited by 241
Meur, N. L., Holder‐Espinasse, M., Jaillard, S., Goldenberg, A., Joriot, S., Amati‐Bonneau, P., Guichet, A., Barth, M., Charollais, A., Journel, H., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2009.069732 · Cited by 228
Fine, S. E., Weissman, A., Gerdes, M., Pinto‐Martin, J. A., Zackai, E. H., McDonald‐McGinn, D. M., & Emanuel, B. S. (2005) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-005-5036-9 · Cited by 222
Autistic Spectrum Disorders in Velo-cardio Facial Syndrome (22q11.2 Deletion)
Antshel, K. M., Aneja, A., Strunge, L., Peebles, J., Fremont, W. P., Stallone, K., AbdulSabur, N., Higgins, A. M., Shprintzen, R. J., & Kates, W. R. (2007) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-006-0308-6 · Cited by 183
Penetrance for copy number variants associated with schizophrenia
Vassos, E., Collier, D. A., Holden, S., Patch, C., Rujescu, D., St Clair, D., & Lewis, C. M. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq259 · Cited by 182
DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder
Hennah, W., Thomson, P. A., McQuillin, A., Bass, N. J., Loukola, A., Anjorin, A., Blackwood, D., Curtis, D., Deary, I. J., Harris, S. E., et al. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.22 · Cited by 165
Schizophrenia and mental handicap: an historical review, with implications for further research
Turner, T. H. (1989) · Psychological Medicine · doi:10.1017/s0033291700012344 · Cited by 150
Murphy, K. C., & Owen, M. J. (2001) · The British Journal of Psychiatry · doi:10.1192/bjp.179.5.397 · Cited by 144
Mefford, H. C., Cooper, G. M., Zerr, T., Smith, J. D., Baker, C., Shafer, N., Thorland, E. C., Skinner, C., Schwartz, C. E., Nickerson, D. A., et al. (2009) · Genome Research · doi:10.1101/gr.094987.109 · Cited by 132
Chromosomal abnormalities and mental illness
MacIntyre, D. J., Blackwood, D., Porteous, D. J., Pickard, B. S., & Muir, W. J. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001232 · Cited by 107
Traylor, R. N., Fan, Z., Hudson, B., Rosenfeld, J. A., Shaffer, L. G., Torchia, B. S., & Ballif, B. C. (2009) · Molecular Cytogenetics · doi:10.1186/1755-8166-2-17 · Cited by 104
Self-citationPhenotypic and genetic complexity of psychosis
Craddock, N. J., O’Donovan, M. C., & Owen, M. J. (2007) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.106.033761 · Cited by 103
Molecular characterization of de novo secondary trisomy 13.
Shaffer, L. G., McCaskill, C., Han, J., Choo, K. H. A., Cutillo, D. M., Donnenfeld, A. E., Weiss, L., & Dyke, D. L. V. (1994) · PubMed Central · Cited by 101
Self-citationSevere mental retardation, seizures, and hypotonia due to deletions of MEF2C
Nowakowska, B., Obersztyn, E., Szymańska, K., Bekiesińska‐Figatowska, M., Xia, Z., Ricks, C. B., Bocian, E., Stockton, D. W., Szczałuba, K., Nawara, M., et al. (2010) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31071 · Cited by 97
Identification of a previously unrecognized microdeletion syndrome of 16q11.2q12.2
Ballif, B. C., Theisen, A. P., McDonald‐McGinn, D. M., Zackai, E. H., Hersh, J. H., Bejjani, B. A., & Shaffer, L. G. (2008) · Clinical Genetics · doi:10.1111/j.1399-0004.2008.01094.x · Cited by 86
Self-citationComparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH
Neill, N. J., Torchia, B. S., Bejjani, B. A., Shaffer, L. G., & Ballif, B. C. (2010) · Molecular Cytogenetics · doi:10.1186/1755-8166-3-11 · Cited by 64
Self-citationNeuroanatomy of comorbid schizophrenia and learning disability: a controlled study
Sanderson, T., Best, J. J. K., Doody, G. A., Owens, D. G. C., & Johnstone, E. C. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01049-1 · Cited by 63
Moorhead, T. W. J., Job, D. E., Whalley, H. C., Sanderson, T. L., Johnstone, E. C., & Lawrie, S. M. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2003.12.012 · Cited by 56
5q14.3 Deletion Manifesting as Mitochondrial Disease and Autism: Case Report
Ezugha, H., Goldenthal, M. J., Valencia, I., Anderson, C. E., Legido, A., & Marks, H. G. (2010) · Journal of Child Neurology · doi:10.1177/0883073809361165 · Cited by 48
Cited by
Sorted by citations
CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics
Malhotra, D., & Sebat, J. (2012) · Cell · doi:10.1016/j.cell.2012.02.039 · Cited by 854
The genetics of bipolar disorder
Gordovez, F. J. A., & McMahon, F. J. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0634-7 · Cited by 284
Heterogeneity within Autism Spectrum Disorders: What have We Learned from Neuroimaging Studies?
Lenroot, R., & Yeung, P. K. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00733 · Cited by 256
Collins, R. L., Brand, H., Redin, C. E., Hanscom, C., Antolik, C. W., Stone, M. R., Glessner, J., Mason, T., Pregno, G., Dorrani, N., et al. (2017) · Genome biology · doi:10.1186/s13059-017-1158-6 · Cited by 208
Self-domestication in Homo sapiens: Insights from comparative genomics
Theofanopoulou, C., Gastaldon, S., O’Rourke, T., Samuels, B. D., Messner, A., Martins, P. T., Delogu, F., Alamri, S., & Boeckx, C. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185306 · Cited by 174
Metadata
- Authors
- Sahoo, T., Theisen, A., Rosenfeld, J. A., Lamb, A. N., Ravnan, J. B., Schultz, R. A., Torchia, B. S., Neill, N., Casci, I., Bejjani, B. A., & Shaffer, L. G.
- Corresponding author
- Shaffer, Lisa G.
- Venue
- Genetics in Medicine
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 13
- Issue
- 10
- Pages
- 868-880
- ISSN
- 1098-3600 (ISSN-L)
- OpenAlex
- W2054476466
- Cited by
- 115
- References
- 52
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 2 · 2021: 12 · 2020: 11 · 2019: 5 · 2018: 3 · 2017: 13 · 2016: 7 · 2015: 5 · 2014: 9 · 2013: 19 · 2012: 10
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Genetics in Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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 › Genome Rearrangement Algorithms
- Keywords
- copy number variation, schizophrenia, 1q21.1, 15q11.2, 15q13.3, 16p11.2, 22q11.2, developmental delay, intellectual disability, autism spectrum disorder, congenital malformations, pleiotropy, neurodevelopmental disorders, speech delay, behavioral problems
- MeSH terms
- Adolescent, Behavioral Symptoms, Child, Developmental Disabilities, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Female, Humans, Infant, Infant, Newborn, Language Development Disorders, Male, Schizophrenia, Genetic Predisposition to Disease, Heredity, Comparative Genomic Hybridization, Young Adult, Genetic Loci, Genetic Association Studies, DNA Copy Number Variations, Chromosome Duplication
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
