The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Microdeletions of 3q29 Confer High Risk for Schizophrenia
Open accessAbstract
Schizophrenia (SZ) is a severe psychiatric illness that affects approximately 1% of the population and has a strong genetic underpinning. Recently, genome-wide analysis of copy-number variation (CNV) has implicated rare and de novo events as important in SZ. Here, we report a genome-wide analysis of 245 SZ cases and 490 controls, all of Ashkenazi Jewish descent. Because many studies have found an excess burden of large, rare deletions in cases, we limited our analysis to deletions over 500 kb in size. We observed seven large, rare deletions in cases, with 57% of these being de novo. We focused on one 836 kb de novo deletion at chromosome 3q29 that falls within a 1.3-1.6 Mb deletion previously identified in children with intellectual disability (ID) and autism, because increasing evidence suggests an overlap of specific rare copy-number variants (CNVs) between autism and SZ. By combining our data with prior CNV studies of SZ and analysis of the data of the Genetic Association Information Network (GAIN), we identified six 3q29 deletions among 7545 schizophrenic subjects and one among 39,748 controls, resulting in a statistically significant association with SZ (p = 0.02) and an odds ratio estimate of 17 (95% confidence interval: 1.36-1198.4). Moreover, this 3q29 deletion region contains two linkage peaks from prior SZ family studies, and the minimal deletion interval implicates 20 annotated genes, including PAK2 and DLG1, both paralogous to X-linked ID genes and now strong candidates for SZ susceptibility.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“In schizophrenia, three genomic regions were significant (Table S6B), all corresponding to CNVs that have been previously implicated in schizophrenia at 3q29 (Mulle et al., 2010), 7q36.3 (Vacic et al., 2011), and 16p11.2 (McCarthy et al., 2009).”
From High frequencies of de novo CNVs in bipolar disorder and schizophrenia (2011) · cites this paper as Mulle et al., 2010
In the citing paper
“several individual CNV loci have been strongly implicated as risk factors for schizophrenia with high degrees of statistical confidence. These include deletions at 1q21.1, NRXN1, 3q29, 15q11.2, 15q13.3, 22q11.2 and duplications at VIPR2, 16p11.2, 16p13.1 and 15q11-q13.2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [6]
In the citing paper
“CNVs spanning DLG1 and DLG2 have been reported before in schizophrenia4, 6, 17”
From De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia (2012) · cites this paper as [6]
In the citing paper
“yet even the largest genome-wide scans (sample sizes typically <10,000) remain under-powered to robustly confirm genetic association for the majority of pathogenic CNVs reported so far, particularly for those with low frequencies (<0.5% in cases) or intermediate effect sizes (odds ratios 2–10).”
From Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects (2017) · cites this paper as [8]
Citations
Cites
Hapeman, D. E., & Agresti, A. (1991) · Technometrics · doi:10.1080/00401706.1991.10484817 · Cited by 9,407
Agresti, A. (2002) · Wiley Series in Probability and Statistics · doi:10.1002/0471249688 · Cited by 6,746
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
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
Common variants on chromosome 6p22.1 are associated with schizophrenia
Shi, J., Levinson, D. F., Duan, J., Sanders, A. R., Zheng, Y., Pe’er, I., Dudbridge, F., Holmans, P., Whittemore, A. S., Mowry, B. J., et al. (2009) · Nature · doi:10.1038/nature08192 · Cited by 1,179
Schizophrenia: The epigenetic puzzle
Haier, R. J. (1982) · Psychiatry Research · doi:10.1016/0165-1781(92)90099-o · Cited by 1,171
Hapeman, D. E., & Agresti, A. (1991) · Technometrics · doi:10.2307/1269056 · Cited by 814
Strong association of de novo copy number mutations with sporadic schizophrenia
Xu, B., Roos, J. L., Levy, S., van Rensburg, E. J., Gogos, J. A., & Karayiorgou, M. (2008) · Nature Genetics · doi:10.1038/ng.162 · Cited by 813
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
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
Categorical Data Analysis, Second Edition
Chimka, J. R. (2003) · IIE Transactions · doi:10.1080/07408170390206977-4700 · Cited by 604
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
A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures.
Sharp, A. J., Mefford, H. C., Li, K., Baker, C., Skinner, C., Stevenson, R. E., Schroer, R. J., Novara, F., De Gregori, M., Ciccone, R., et al. (2008) · Nature Genetics · doi:10.1038/ng.93 · Cited by 582
Analysis of array CGH data: from signal ratio to gain and loss of DNA regions
Hupé, P., Stransky, N., Thiery, J. P., Radvanyi, F., & Barillot, E. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth418 · Cited by 521
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
Guilmatre, A., Dubourg, C., Mosca, A.-L., Legallic, S., Goldenberg, A., Drouin-Garraud, V., Layet, V., Rosier, A., Briault, S., Bonnet-Brilhault, F., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.80 · Cited by 429
Miller, D. T., Shen, Y., Weiss, L. A., Korn, J., Anselm, I., Bridgemohan, C., Cox, G. F., Dickinson, H., Gentile, J., Harris, D. J., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.059907 · Cited by 427
Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1
Hayashi-Takagi, A., Takaki, M., Graziane, N., Seshadri, S., Murdoch, H., Dunlop, A. J., Makino, Y., Seshadri, A. J., Ishizuka, K., Srivastava, D. P., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2487 · Cited by 399
Fallin, M. D., Lasseter, V. K., Avramopoulos, D., Nicodemus, K. K., Wolyniec, P. S., McGrath, J. A., Steel, G., Nestadt, G., Liang, K., Huganir, R. L., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/497703 · Cited by 398
Self-citationBallif, 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
3q29 Microdeletion Syndrome: Clinical and Molecular Characterization of a New Syndrome
Willatt, L. R., Cox, J. J., Barber, J. C. K., Cabanas, E. D., Collins, A., Donnai, D., FitzPatrick, D. R., Maher, E., Martin, H., Parnau, J., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/431653 · Cited by 292
Comparative genomics of autism and schizophrenia
Crespi, B., Stead, P., & Elliot, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906080106 · Cited by 262
Ben-Shachar, S., Lanpher, B., German, J. R., Qasaymeh, M., Potocki, L., Nagamani, S. C. S., Franco, L. M., Malphrus, A., Bottenfield, G. W., Spence, J. E., et al. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.064378 · Cited by 261
Atzmon, G., Hao, L., Pe'er, I., Velez, C., Pearlman, A., Palamara, P. F., Morrow, B., Friedman, E., Oddoux, C., Burns, E., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.04.015 · Cited by 260
Neurexin 1 (NRXN1) Deletions in Schizophrenia
Kirov, G., Rujescu, D., Ingason, A., Collier, D. A., O'Donovan, M. C., & Owen, M. J. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbp079 · Cited by 235
The Future of Psychiatric Research: Genomes and Neural Circuits
Akil, H., Brenner, S., Kandel, E. R., Kendler, K. S., King, M., Scolnick, E. M., Watson, J. D., & Zoghbi, H. Y. (2010) · Science · doi:10.1126/science.1188654 · Cited by 204
A 15q13.3 microdeletion segregating with autism
Pagnamenta, A. T., Wing, K., Akha, E. S., Knight, S. J. L., Bölte, S., Schmötzer, G., Duketis, E., Poustka, F., Klauck, S. M., Poustka, A., et al. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.228 · Cited by 177
Lin, S., Chakravarti, A., & Cutler, D. J. (2004) · Nature Genetics · doi:10.1038/ng1457 · Cited by 154
Self-citationSparse representation and Bayesian detection of genome copy number alterations from microarray data
Piqué-Regi, R., Monso-Varona, J., Ortega, A., Seeger, R. C., Triche, T. J., & Asgharzadeh, S. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btm601 · Cited by 131
The role of SAP97 in synaptic glutamate receptor dynamics
Howard, M. A., Elias, G. M., Elias, L. A. B., Swat, W., & Nicoll, R. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914422107 · Cited by 129
Toyooka, K., Iritani, S., Makifuchi, T., Shirakawa, O., Kitamura, N., Maeda, K., Nakamura, R., Niizato, K., Watanabe, M., Kakita, A., et al. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01181.x · Cited by 121
Fallin, M. D., Lasseter, V. K., Wolyniec, P. S., McGrath, J. A., Nestadt, G., Valle, D. L., Liang, K., & Pulver, A. E. (2003) · The American Journal of Human Genetics · doi:10.1086/378158 · Cited by 105
Self-citationTian, C., Kosoy, R., Nassir, R., Lee, A., Villoslada, P., Klareskog, L., Hammarström, L. L. G., Garchon, H., Pulver, A. E., Ransom, M., et al. (2009) · Molecular Medicine · doi:10.2119/molmed.2009.00094 · Cited by 100
Self-citationGenome scan for susceptibility loci for schizophrenia and bipolar disorder
Bailer, U. F., Leisch, F., Meszaros, K., Lenzinger, E., Willinger, U., Strobl, R., Heiden, A. M., Gebhardt, C., Döge, E., Fuchs, K., et al. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01320-3 · Cited by 96
Molecular mechanisms underlying glutamatergic dysfunction in schizophrenia: therapeutic implications
Gaspar, P. A., Bustamante, M. L., Hernán Silva, I., & Aboitiz, F. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06325.x · Cited by 91
GluR1 Controls Dendrite Growth through Its Binding Partner, SAP97
Zhou, W., Zhang, L., Guoxiang, X., Mojsilovic‐Petrovic, J., Takamaya, K., Sattler, R., Huganir, R. L., & Kalb, R. G. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3434-08.2008 · Cited by 63
Devlin, B., Bacanu, S., Roeder, K., Reimherr, F. W., Wender, P. H., Galke, B. L., Novasad, D., Chu, A., Tcuenco, K. T., Tiobek, S., et al. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001056 · Cited by 61
Nash, J. E., Appleby, V. J., Corrêa, S. A. L., Wu, H., Fitzjohn, S. M., Garner, C. C., Collingridge, G. L., & Molnár, E. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06480.x · Cited by 56
An association analysis of synapse-associated protein 97 (SAP97) gene in schizophrenia
Sato, J., Shimazu, D., Yamamoto, N., & Nishikawa, T. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0085-9 · Cited by 44
Shin, E., Shim, E., Lee, C., Kim, H. K., & Kim, E. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.12.066 · Cited by 39
Baynam, G., Goldblatt, J., & Townshend, S. (2006) · Clinical Dysmorphology · doi:10.1097/01.mcd.0000198934.55071.ee · Cited by 28
Dissecting the many genetic faces of schizophrenia
Rujescu, D., & Collier, D. A. (2009) · Epidemiologia e Psichiatria Sociale · doi:10.1017/s1121189x00000944 · Cited by 20
Possible linkage of schizophrenia and bipolar affective disorder to chromosome 3q29
Schosser, A., Fuchs, K., Leisch, F., Bailer, U. F., Meszaros, K., Lenzinger, E., Willinger, U., Strobl, R., Heiden, A. M., Gebhardt, C., et al. (2004) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2003.11.004 · Cited by 18
Additional support for linkage of schizophrenia and bipolar disorder to chromosome 3q29
Schosser, A., Fuchs, K., Scharl, T., Leisch, F., Bailer, U. F., Kasper, S. F., Sieghart, W., Hornik, K., & Aschauer, H. N. (2007) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2007.01.004 · Cited by 8
Cited by
Sorted by citations
Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap
Gandal, M. J., Haney, J. R., Parikshak, N. N., Leppa, V., Ramaswami, G., Hartl, C., Schork, A. J., Appadurai, V., Buil, A., Werge, T. M., et al. (2018) · Science · doi:10.1126/science.aad6469 · Cited by 1,095
Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
Marshall, C. R., Howrigan, D. P., Merico, D., Thiruvahindrapuram, B., Wu, W., Greer, D. S., Antaki, D., Shetty, A., Holmans, P. A., Pinto, D., et al. (2017) · Nature Genetics · doi:10.1038/ng.3725 · Cited by 1,058
Self-citationCNVs: 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
Kirov, G., Pocklington, A. J., Holmans, P., Ivanov, D., Ikeda, M., Ruderfer, D., Moran, J., Chambert, K., Toncheva, D., Georgieva, L., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.154 · Cited by 844
“33 CNVs spanning DLG1 and DLG2 have been reported before in schizophrenia 4,6,17 whereas other members of the family ( DLG3 and DLGAP2 ) have been implicated in mental retardation 35 and autism.”
Neurodevelopmental model of schizophrenia: update 2012
Rapoport, J. L., Giedd, J. N., & Gogtay, N. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.23 · Cited by 790
Metadata
- Authors
- Mulle, J. G., Dodd, A. F., McGrath, J. A., Wolyniec, P. S., Mitchell, A. A., Shetty, A. C., Sobreira, N. L., Valle, D., Rudd, M. K., Satten, G., Cutler, D. J., Pulver, A. E., & Warren, S. T.
- Affiliations
- Emory University (US)
- Johns Hopkins University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Mulle, Jennifer Gladys
- Warren, Stephen T.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 87
- Issue
- 2
- Pages
- 229-236
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2917706
- OpenAlex
- W2094942174
- Cited by
- 223
- References
- 46
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 8 · 2023: 10 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 15 · 2017: 12 · 2016: 9 · 2015: 19 · 2014: 16 · 2013: 31 · 2012: 30
- FWCI
- 16.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (F32MH080583, R01MH080129, R01MH083722)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F31HD068133)
- 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, copy number variation, de novo deletion, Ashkenazi Jews, genetic susceptibility, PAK2, DLG1, intellectual disability, autism spectrum disorder
- MeSH terms
- Chromosomes, Human, Pair 3, Humans, Schizophrenia, Reproducibility of Results, Case-Control Studies, Sequence Deletion, Genetic Predisposition to Disease, Base Pairing, Physical Chromosome Mapping, Young Adult, Genetic Loci, DNA Copy Number Variations
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
