The conundrums of understanding genetic risks for autism spectrum disorders
Open accessAbstract
Recent advances in the genetics of autism spectrum disorders (ASDs) are offering new valuable insights into molecular and cellular mechanisms of pathology. At the same time, the emerging data challenge long-standing diagnostic conventions and the notion of phenotypic specificity. This review addresses the particular issues that attend gene discovery in neuropsychiatric and neurodevelopmental disorders and ASDs in particular, summarizes recent findings in human genetics broadly that are driving the reevaluation of the conventional wisdom regarding the allelic architecture of common psychiatric conditions, reviews selected discoveries in ASDs and their relevance to models of pathology, highlights the conceptual and practical issues raised by the observation of a convergence of ASD genetic risks with distinct psychiatric disorders, and considers the important interplay of studies of neurobiology and genetics in clarifying and extending our understanding of social disability syndromes.
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
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?
ASD is often caused by newly arising CNVs or rare germline mutations, particularly in sperm of older fathers.
“ASD is often due to newly arising gene copy number variants (CNVs) — such as a deletion or duplication of a region of a chromosome — or a rare mutation that arises in the germ cell, particularly in sperm of older fathers5–10.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [5]
Rare genetic variations play a significant part in the aetiology of ASD.
“Rare genetic variations play a significant part in the aetiology of ASD.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [5]
Rare mutations in NLGN4, NLGN3, NRXN1, SHANK2, SHANK3, and CNTNAP2 have been identified in multiple individuals with ASD, suggesting these mutations contribute to the disorder.
“More subtle, rare mutations in NLGN4, NLGN3, NRXN1, SHANK2, SHANK3, CNTNAP2 (ref. 5) have also been identified in multiple individuals with ASD, suggesting that these mutations also contribute these disorders.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [5]
Mutations in multiple synaptic cell adhesion molecules and PSD components are associated with ASD.
“Mutations in multiple synaptic cell adhesion molecules and components of the PSD are associated with ASD.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [5]
Several de novo CNVs associated with ASD have been detected multiple times, including CNVs at 16p11.2, 15q11-13, 22q11.2, deletions at NRXN1, and duplications at 7q11.23.
“Several de novo CNVs that are associated with ASD have been detected multiple times, including CNVs at 16p11.2, 15q11–13, 22q11.2, deletions at NRXN1, and duplications at 7q11.235,32.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [5]
Rare mutations in multiple members of the neuroligin and neurexin families of synaptic adhesion molecules have repeatedly been found to be associated with ASD.
“Rare mutations in multiple members of the neuroligin and neurexin families of synaptic adhesion molecules have repeatedly been found to be associated with ASD5.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [5]
Rare mutations linked to ASD occur in SHANK2, SHANK3, and SHANK1.
“Rare mutations associated with ASD have been found in SHANK2 and SHANK3 (ref. 5), and recently in SHANK1 (ref. 46).”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [5]
A model attributes phenotypic variability to a combination of locus heterogeneity and pleiotropic effects of individual alleles.
“Another model has been proposed that attributes phenotypic variability to a combination of locus heterogeneity and pleiotropic effects of the individual alleles (State and Levitt, 2011).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as State and Levitt, 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Finding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336 · see citing works
The Future of Genetic Studies of Complex Human Diseases
Risch, N., & Merikangas, K. (1996) · Science · doi:10.1126/science.273.5281.1516 · Cited by 5,355 · see citing works
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795 · see citing works
Functional impact of global rare copy number variation in autism spectrum disorders
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., et al. (2010) · Nature · doi:10.1038/nature09146 · Cited by 2,013 · see citing works
Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
Voineagu, I., Wang, X., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., Mill, J., Cantor, R. M., Blencowe, B. J., & Geschwind, D. H. (2011) · Nature · doi:10.1038/nature10110 · Cited by 1,874 · see citing works
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
Study, P. A. R. I. S., Jamain, S., Quach, H., Betancur, C., Råstam, M., Colineaux, C., Gillberg, I. C., Soderstrom, H., Giros, B., Leboyer, M., et al. (2003) · Nature Genetics · doi:10.1038/ng1136 · Cited by 1,851 · see citing works
Structural Variation of Chromosomes in Autism Spectrum Disorder
Marshall, C. R., Noor, A., Vincent, J. B., Lionel, A. C., Feuk, L., Skaug, J., Shago, M., Moessner, R., Pinto, D., Ren, Y., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.12.009 · Cited by 1,815 · see citing works
Association between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Saemundsen, E., Stefansson, H., Ferreira, M. A. R., Green, T., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa075974 · Cited by 1,666 · see citing works
Durand, C. M., Betancur, C., Boeckers, T. M., Bockmann, J., Chaste, P., Fauchereau, F., Nygren, G., Rastam, M., Gillberg, I. C., Anckarsäter, H., et al. (2007) · Nature Genetics · doi:10.1038/ng1933 · Cited by 1,602 · see citing works
Evolution of the neocortex: a perspective from developmental biology
Rakic, P. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2719 · Cited by 1,565 · see citing works
Genetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452 · see citing works
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
Glessner, J. T., Wang, K., Cai, G., Korvatska, O., Kim, C. E., Wood, S., Zhang, H., Estes, A., Brune, C. W., Bradfield, J. P., et al. (2009) · Nature · doi:10.1038/nature07953 · Cited by 1,421 · see citing works
Autism spectrum disorders: developmental disconnection syndromes
Geschwind, D. H., & Levitt, P. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.01.009 · Cited by 1,411 · see citing works
Self-citationMapping autism risk loci using genetic linkage and chromosomal rearrangements
The Autism Genome Project Consortium (2007) · Nature Genetics · doi:10.1038/ng1985 · Cited by 1,402 · see citing works
Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., Chu, S. H., Moreau, M. P., Gupta, A. R., Thomson, S. A., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.002 · Cited by 1,263 · see citing works
Self-citationReversal of Neurological Defects in a Mouse Model of Rett Syndrome
Guy, J., Gan, J., Selfridge, J., Cobb, S., & Bird, A. (2007) · Science · doi:10.1126/science.1138389 · Cited by 1,230 · see citing works
On the allelic spectrum of human disease
Reich, D. E., & Lander, E. S. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02410-6 · Cited by 1,185 · see citing works
Uncovering the roles of rare variants in common disease through whole-genome sequencing
Cirulli, E. T., & Goldstein, D. B. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2779 · Cited by 1,136 · see citing works
Common genetic variants on 5p14.1 associate with autism spectrum disorders
Wang, K., Zhang, H., Ma, D., Bucan, M., Glessner, J. T., Abrahams, B. S., Salyakina, D., Imielinski, M., Bradfield, J. P., Sleiman, P. M. A., et al. (2009) · Nature · doi:10.1038/nature07999 · Cited by 989 · see citing works
Self-citationCommon Genetic Variation and Human Traits
Goldstein, D. B. (2009) · New England Journal of Medicine · doi:10.1056/nejmp0806284 · Cited by 918 · see citing works
Buie, T., Campbell, D. B., Fuchs, G. J., Furuta, G. T., Levy, J., VandeWater, J., Whitaker, A. H., Atkins, D., Bauman, M. L., Beaudet, A. L., et al. (2010) · Pediatrics · doi:10.1542/peds.2009-1878c · Cited by 872 · see citing works
Self-citationPober, B. R. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0903074 · Cited by 848 · see citing works
Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene
Alarcón, M., Abrahams, B. S., Stone, J. L., Duvall, J. A., Perederiy, J. V., Bomar, J. M., Sebat, J., Wigler, M., Martin, C. L., Ledbetter, D. H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.005 · Cited by 818 · see citing works
Rare independent mutations in renal salt handling genes contribute to blood pressure variation
Ji, W., Foo, J. N., O'Roak, B. J., Zhao, H., Larson, M. G., Simon, D. B., Newton-Cheh, C., State, M. W., Levy, D., & Lifton, R. P. (2008) · Nature Genetics · doi:10.1038/ng.118 · Cited by 812 · see citing works
Self-citationRecurrent 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 · see citing works
Laumonnier, F., Bonnet-Brilhault, F., Gomot, M., Blanc, R., David, A., Moizard, M.-P., Raynaud, M., Ronce, N., Lemonnier, E., Calvas, P., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/382137 · Cited by 768 · see citing works
Recurrent 16p11.2 microdeletions in autism
Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., Brune, C., Badner, J. A., Gilliam, T. C., Nowak, N. J., Cook, E. H., Dobyns, W. B., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm376 · Cited by 731 · see citing works
Rare de novo and transmitted copy-number variation in autistic spectrum disorders
Levy, D., Ronemus, M., Yamrom, B., Lee, Y.-H., Leotta, A., Kendall, J., Marks, S., Lakshmi, B., Pai, D., Ye, K., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.015 · Cited by 712 · see citing works
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 · see citing works
Gilman, S. R., Iossifov, I., Levy, D., Ronemus, M., Wigler, M., & Vitkup, D. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.021 · Cited by 701 · see citing works
A functional genetic link between distinct developmental language disorders
Vernes, S. C., Newbury, D. F., Abrahams, B. S., Winchester, L., Nicod, J., Groszer, M., Alarcón, M., Oliver, P. L., Davies, K. E., Geschwind, D. H., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802828 · Cited by 676 · see citing works
Association Between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Sæmundsen, E., Stefánsson, H., Ferreira, M. A. R., Green, T. J., et al. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000316305.61461.6f · Cited by 647 · see citing works
Population genetics—making sense out of sequence
Chakravarti, A. (1999) · Nature Genetics · doi:10.1038/4482 · Cited by 643 · see citing works
Bourgeron, T. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.06.003 · Cited by 637 · cited 1× · see citing works
“However, as the molecular underpinnings of these syndromes have been elaborated, they have tended to converge on alterations in the assembly and functioning of synapse”
Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2
Strauss, K. A., Puffenberger, E. G., Huentelman, M. J., Gottlieb, S., Dobrin, S. E., Parod, J. M., Stephan, D. A., & Morton, D. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052773 · Cited by 630 · see citing works
A genome-wide linkage and association scan reveals novel loci for autism
The Gene Discovery Project of Johns Hopkins & the Autism Consortium, Weiss, L. A., & Arking, D. E. (2009) · Nature · doi:10.1038/nature08490 · Cited by 619 · see citing works
Large, rare chromosomal deletions associated with severe early-onset obesity
Bochukova, E. G., Huang, N., Keogh, J., Henning, E., Purmann, C., Blaszczyk, K., Saeed, S., Hamilton-Shield, J., Clayton-Smith, J., O’Rahilly, S., et al. (2010) · Nature · doi:10.1038/nature08689 · Cited by 613 · see citing works
A genome-wide scan for common alleles affecting risk for autism
Anney, R., Klei, L., Pinto, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., Sykes, N., Pagnamenta, A. T., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq307 · Cited by 593 · see citing works
Arking, D. E., Cutler, D. J., Brune, C. W., Teslovich, T. M., West, K., Ikeda, M., Rea, A., Guy, M., Lin, S., Cook, E. H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.015 · Cited by 590 · see citing works
Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation
Berkel, S., Marshall, C. R., Weiss, B., Howe, J., Roeth, R., Moog, U., Endris, V., Roberts, W., Szatmari, P., Pinto, D., et al. (2010) · Nature Genetics · doi:10.1038/ng.589 · Cited by 563 · see citing works
Luiselli, J., Happe, F. G. E., Hurst, H., et al. (2012) · Springer eBooks · doi:10.1007/978-1-4419-1698-3_101563 · Cited by 539 · see citing works
Bakkaloglu, B., O'Roak, B. J., Louvi, A., Gupta, A. R., Abelson, J. F., Morgan, T. M., Chawarska, K., Klin, A., Ercan-Sencicek, A. G., Stillman, A. A., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.09.017 · Cited by 537 · see citing works
Self-citationGeschwind, D. H. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.053107.121225 · Cited by 512 · see citing works
A genetic variant that disrupts <i>MET</i> transcription is associated with autism
Campbell, D. B., Sutcliffe, J. S., Ebert, P. J., Militerni, R., Bravaccio, C., Trillo, S., Elia, M., Schneider, C., Melmed, R., Sacco, R., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605296103 · Cited by 401 · see citing works
Self-citationDeletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia
Moreno-De-Luca, D., Mulle, J. G., Kaminsky, E. B., Sanders, S. J., Myers, S. M., Adam, M. P., Pakula, A. T., Eisenhauer, N. J., Uhas, K., Weik, L., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.10.004 · Cited by 324 · see citing works
Novel de novo SHANK3 mutation in autistic patients
Gauthier, J., Spiegelman, D., Piton, A., Lafrenière, R. G., Laurent, S., St‐Onge, J., Lapointe, L., Hamdan, F. F., Cossette, P., Mottron, L., et al. (2009) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30822 · Cited by 321 · see citing works
Moss, J. F., & Howlin, P. (2009) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2009.01197.x · Cited by 313 · see citing works
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 · see citing works
Deletions of NRXN1 (neurexin‐1) predispose to a wide spectrum of developmental disorders
Ching, M. S. L., Shen, Y., Tan, W., Jeste, S., Morrow, E. M., Chen, X., Mukaddes, N. M., Yoo, S.-Y., Hanson, E. M., Hundley, R. J., et al. (2010) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31063 · Cited by 292 · see citing works
Sebat, J., Levy, D. L., & McCarthy, S. E. (2009) · Trends in Genetics · doi:10.1016/j.tig.2009.10.004 · Cited by 260 · see citing works
Is schizophrenia on the autism spectrum?
King, B. H., & Lord, C. (2010) · Brain Research · doi:10.1016/j.brainres.2010.11.031 · Cited by 253 · see citing works
Scott-Van Zeeland, A. A., Abrahams, B. S., Alvarez-Retuerto, A. I., Sonnenblick, L. I., Rudie, J. D., Ghahremani, D., Mumford, J. A., Poldrack, R. A., Dapretto, M., Geschwind, D. H., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001344 · Cited by 252 · see citing works
Levitt, P., & Campbell, D. B. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37934 · Cited by 234 · see citing works
Self-citationNeuroscience in the era of functional genomics and systems biology
Geschwind, D. H., & Konopka, G. (2009) · Nature · doi:10.1038/nature08537 · Cited by 213 · see citing works
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 198 · see citing works
Reversing Neurodevelopmental Disorders in Adults
Ehninger, D., Li, W., Fox, K., Stryker, M. P., & Silva, A. J. (2008) · Neuron · doi:10.1016/j.neuron.2008.12.007 · Cited by 196 · see citing works
Effect of Simvastatin on Cognitive Functioning in Children With Neurofibromatosis Type 1
Krab, L. C. (2008) · JAMA · doi:10.1001/jama.300.3.287 · Cited by 194 · see citing works
Disruption of cerebral cortex MET signaling in autism spectrum disorder
Campbell, D. B., D'Oronzio, R., Garbett, K., Ebert, P. J., Mirnics, K., Levitt, P., & Persico, A. M. (2007) · Annals of Neurology · doi:10.1002/ana.21180 · Cited by 193 · see citing works
Self-citationFernandez, T. V., Morgan, T. M., Davis, N., Klin, A. J., Morris, A., Farhi, A., Lifton, R. P., & State, M. W. (2004) · The American Journal of Human Genetics · doi:10.1086/421474 · Cited by 191 · see citing works
Self-citationGenetic advances in autism: heterogeneity and convergence on shared pathways
Bill, B. R., & Geschwind, D. H. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.04.004 · Cited by 164 · see citing works
The genetics of child psychiatric disorders: focus on autism and Tourette syndrome
State, M. W. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.004 · Cited by 162 · see citing works
Self-citationCampbell, D. B., Li, C., Sutcliffe, J. S., Persico, A. M., & Levitt, P. (2008) · Autism Research · doi:10.1002/aur.27 · Cited by 154 · see citing works
Self-citationDisruption of contactin 4 in three subjects with autism spectrum disorder
Roohi, J., Montagna, C., Tegay, D. H., Palmer, L. E., DeVincent, C. J., Pomeroy, J. C., Christian, S. L., Nowak, N., & Hatchwell, E. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2008.057505 · Cited by 151 · see citing works
Genetics and intermediate phenotypes of the schizophrenia—bipolar disorder boundary
Ivleva, E. I., Morris, D. W., Moates, A. F., Suppes, T. M., Thaker, G. K., & Tamminga, C. A. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.11.022 · Cited by 150 · see citing works
Rethinking the nature of genetic vulnerability to autistic spectrum disorders
Skuse, D. H. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.06.003 · Cited by 147 · see citing works
Campbell, D. B., Buie, T. M., Winter, H., Bauman, M., Sutcliffe, J. S., Perrin, J. M., & Levitt, P. (2009) · Pediatrics · doi:10.1542/peds.2008-0819 · Cited by 145 · see citing works
Self-citationRegulation of MET by FOXP2, Genes Implicated in Higher Cognitive Dysfunction and Autism Risk
Mukamel, Z., Konopka, G., Wexler, E., Osborn, G. E., Dong, H., Bergman, M. Y., Levitt, P. R., & Geschwind, D. H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0181-11.2011 · Cited by 116 · see citing works
Self-citationMolecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex
Roll, P., Vernes, S. C., Bruneau, N., Cillario, J., Ponsole-Lenfant, M., Massacrier, A., Rudolf, G., Khalifé, M., Hirsch, É., Fisher, S. E., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq415 · Cited by 114 · see citing works
Qiu, S., Anderson, C. T., Levitt, P., & Shepherd, G. M. G. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6569-10.2011 · Cited by 106 · see citing works
Self-citationDo common variants play a role in risk for autism? Evidence and theoretical musings
Devlin, B., Melhem, N., & Roeder, K. (2011) · Brain Research · doi:10.1016/j.brainres.2010.11.026 · Cited by 105 · see citing works
Association and mutation analyses of 16p11.2 autism candidate genes
Kumar, R. A., Marshall, C. R., Badner, J. A., Babatz, T. D., Mukamel, Z., Aldinger, K. A., Sudi, J., Brune, C. W., Goh, G., KaraMohamed, S., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004582 · Cited by 95 · see citing works
HGF regulates the development of cortical pyramidal dendrites
Gutiérrez, H., Dolcet, X., Tolcos, M., & Davies, A. (2004) · Development · doi:10.1242/dev.01209 · Cited by 91 · see citing works
MET and autism susceptibility: family and case-control studies
Sousa, I., Clark, T., Toma, C., Kobayashi, K., Choma, M., Holt, R., Sykes, N. H., Lamb, J., Bailey, A., Battaglia, A., et al. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.215 · Cited by 90 · see citing works
Stein, M. B., Yang, B.-Z., Chavira, D. A., Hitchcock, C. A., Sung, S. C., Shipon-Blum, E., & Gelernter, J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.11.008 · Cited by 89 · see citing works
Animal models of gene–environment interactions in schizophrenia
Ayhan, Y., Sawa, A., Ross, C. A., & Pletnikov, M. V. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.04.010 · Cited by 87 · see citing works
Judson, M. C., Bergman, M. Y., Campbell, D. B., Eagleson, K. L., & Levitt, P. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21969 · Cited by 80 · see citing works
Self-citationJackson, P. B., Boccuto, L., Skinner, C., Collins, J. S., Neri, G., Gurrieri, F., & Schwartz, C. E. (2009) · Autism Research · doi:10.1002/aur.87 · Cited by 65 · see citing works
Hoekstra, R. A., Happe, F. G. E., Baron‐Cohen, S., & Ronald, A. (2009) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.108.060889 · Cited by 59 · see citing works
Fernandez, T. V., Morgan, T. M., Davis, N., Klin, A. J., Morris, A., Farhi, A., Lifton, R. P., & State, M. W. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.04.021 · Cited by 58 · see citing works
Self-citationJudson, M. C., Eagleson, K. L., Wang, L., & Levitt, P. R. (2010) · The Journal of Comparative Neurology · doi:10.1002/cne.22467 · Cited by 55 · see citing works
Self-citationMECP2 deletions and genotype–phenotype correlation in Rett syndrome
Scala, E., Longo, I., Ottimo, F., Speciale, C., Sampieri, K., Katzaki, E., Artuso, R., Mencarelli, M. A., D'Ambrogio, T., Vonella, G., et al. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32002 · Cited by 52 · see citing works
Hammock, E. A. D., & Levitt, P. R. (2006) · Human Development · doi:10.1159/000095581 · Cited by 46 · see citing works
Self-citationA new synaptic player leading to autism risk: Met receptor tyrosine kinase
Judson, M. C., Eagleson, K. L., & Levitt, P. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9081-8 · Cited by 43 · see citing works
Self-citationBachman, P., Kim, J., Yee, C. M., Therman, S., Manninen, M., Lönnqvist, J. K., Kaprio, J. A., HUTTUNEN, M. O., Näätänen, R., & Cannon, T. D. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.04.006 · Cited by 42 · see citing works
Tyndall, S. J., Patel, S. J., & Walikonis, R. S. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21390 · Cited by 35 · see citing works
Judson, M. C., Amaral, D., & Levitt, P. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhq223 · Cited by 31 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- [68]Pinto D Functional impact of global rare copy number variation in autism spectrum disorders Nature 2010 PMC3021798 20531469
- [82]Vernes SC A functional genetic link between distinct developmental language disorders The New England journal of medicine 2008 359 2337 2345 18987363 PMC2756409
Cited by
Sorted by citations
Lai, M.-C., Lombardo, M. V., & Baron-Cohen, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61539-1 · Cited by 2,371 · see citing works
Most genetic risk for autism resides with common variation
Gaugler, T., Klei, L., Sanders, S. J., Bodea, C. A., Goldberg, A. P., Lee, A. B., Mahajan, M., Manaa, D., Pawitan, Y., Reichert, J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3039 · Cited by 1,239 · see citing works
Willsey, A. J., Sanders, S. J., Li, M., Dong, S., Tebbenkamp, A. T., Muhle, R. A., Reilly, S. K., Lin, L., Fertuzinhos, S., Miller, J. A., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.020 · Cited by 934 · see citing works
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 · see citing works
Activity-dependent neuronal signalling and autism spectrum disorder
Ebert, D. H., & Greenberg, M. E. (2013) · Nature · doi:10.1038/nature11860 · Cited by 666 · see citing works
Hus, V., Gotham, K., & Lord, C. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1719-1 · Cited by 568 · see citing works
Genetic architecture in autism spectrum disorder
Devlin, B., & Scherer, S. W. (2012) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2012.03.002 · Cited by 545 · see citing works
Cotney, J., Muhle, R. A., Sanders, S. J., Liu, L., Willsey, A. J., Niu, W., Liu, W., Klei, L., Lei, J., Yin, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms7404 · Cited by 350 · see citing works
Self-citationBlood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis
Gabriele, S., Sacco, R., & Persico, A. M. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.02.004 · Cited by 346 · see citing works
Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment
Goines, P. E., & Ashwood, P. (2013) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2012.07.006 · Cited by 314 · see citing works
ADHD and autism: differential diagnosis or overlapping traits? A selective review
Taurines, R., Schwenck, C., Westerwald, E., Sachse, M., Siniatchkin, M., & Freitag, C. (2012) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-012-0086-2 · Cited by 301 · see citing works
DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways
Nardone, S., Sharan Sams, D., Reuveni, E., Getselter, D., Oron, O., Karpuj, M., & Elliott, E. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.70 · Cited by 266 · see citing works
Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms
Tordjman, S., Somogyi, E., Coulon, N., Kermarrec, S., Cohen, D., Bronsard, G., Bonnot, O., Weismann-Arcache, C., Botbol, M., Lauth, B., et al. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00053 · Cited by 283 · see citing works
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons
Griesi-Oliveira, K., Acab, A., Gupta, A. R., Sunaga, D. Y., Chailangkarn, T., Nicol, X., Nunez, Y., Walker, M. F., Murdoch, J. D., Sanders, S. J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.141 · Cited by 236 · see citing works
Self-citationAn epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy
Millan, M. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.015 · Cited by 229 · see citing works
Tyszka, J. M., Kennedy, D. P., Paul, L. K., & Adolphs, R. (2014) · Cerebral Cortex · doi:10.1093/cercor/bht040 · Cited by 187 · see citing works
Autism genetics: searching for specificity and convergence
Berg, J. M., & Geschwind, D. H. (2012) · Genome Biology · doi:10.1186/gb-2012-13-7-247 · Cited by 192 · see citing works
Moreno-De-Luca, D., Sanders, S. J., Willsey, A. J., Mulle, J. G., Lowe, J. K., Geschwind, D. H., State, M. W., Martin, C. L., & Ledbetter, D. H. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.138 · Cited by 161 · see citing works
Self-citationThe Emerging Biology of Autism Spectrum Disorders
State, M. W., & Šestan, N. (2012) · Science · doi:10.1126/science.1224989 · Cited by 164 · see citing works
Self-citationEpigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders
Zhu, L., Wang, X., Li, X.-L., Towers, A., Cao, X., Wang, P., Bowman, R., Yang, H., Goldstein, J., Li, Y.-J., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt547 · Cited by 147 · see citing works
Enhanced synapse remodelling as a common phenotype in mouse models of autism
Isshiki, M., Tanaka, S., Kuriu, T., Tabuchi, K., Takumi, T., & Okabe, S. (2014) · Nature Communications · doi:10.1038/ncomms5742 · Cited by 152 · see citing works
Autism-Associated Promoter Variant in MET Impacts Functional and Structural Brain Networks
Rudie, J. D., Hernandez, L. M., Brown, J. A., Beck-Pancer, D., Colich, N. L., Gorrindo, P., Thompson, P. M., Geschwind, D. H., Bookheimer, S. Y., Levitt, P., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.010 · Cited by 142 · see citing works
Self-citationSestan, N., & State, M. W. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.015 · Cited by 127 · see citing works
Self-citationKas, M. J., Glennon, J. C., Buitelaar, J., Ey, E., Biemans, B., Crawley, J., Ring, R. H., Lajonchere, C., Esclassan, F., Talpos, J., et al. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3268-5 · Cited by 132 · see citing works
Spooren, W., Lindemann, L., Ghosh, A., & Santarelli, L. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.09.004 · Cited by 119 · see citing works
Toward an immune-mediated subtype of autism spectrum disorder
McDougle, C. J., Landino, S. M., Vahabzadeh, A., O’Rourke, J., Zurcher, N. R., Finger, B. C., Palumbo, M. L., Helt, J., Mullett, J. E., Hooker, J. M., et al. (2015) · Brain Research · doi:10.1016/j.brainres.2014.09.048 · Cited by 95 · see citing works
Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism
Liu, X., Han, D., Somel, M., Jiang, X., Hu, H., Guijarro, P., Zhang, N., Mitchell, A., Halene, T., Ely, J. J., et al. (2016) · PLOS Biology · doi:10.1371/journal.pbio.1002558 · Cited by 87 · see citing works
Interpreting the role of de novo protein-coding mutations in neuropsychiatric disease
Gratten, J., Visscher, P. M., Mowry, B. J., & Wray, N. R. (2013) · Nature Genetics · doi:10.1038/ng.2555 · Cited by 77 · see citing works
Cappi, C., Brentani, H., Lima, L., Sanders, S. J., Zai, G., Diniz, B. J., Reis, V. N. S., Hounie, A. G., Conceição do Rosário, M., Mariani, D., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.30 · Cited by 71 · see citing works
Noh, H. J., Ponting, C. P., Boulding, H. C., Meader, S., Betancur, C., Buxbaum, J. D., Pinto, D., Marshall, C. R., Lionel, A. C., Scherer, S. W., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003523 · Cited by 54 · see citing works
Guerini, F. R., Bolognesi, E., Chiappedi, M., Ghezzo, A., Canevini, M. P., Mensi, M. M., Vignoli, A., Agliardi, C., Zanette, M., & Clerici, M. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.10.002 · Cited by 39 · see citing works
Hedrick, A., Lee, Y., Wallace, G. L., Greenstein, D., Clasen, L., Giedd, J. N., & Raznahan, A. (2012) · Autism Research · doi:10.1002/aur.1256 · Cited by 35 · see citing works
Genetics of Autism Spectrum Disorders
Rutter, M., & Thapar, A. (2014) · Handbook of Autism and Pervasive Developmental Disorders, Fourth Edition · doi:10.1002/9781118911389.hautc17 · Cited by 31 · see citing works
- Authors
- State, M. W., & Levitt, P.
- Affiliations
- Yale University (US)
- University of Southern California (US)
- Corresponding author
- State, Matthew W
- Levitt, Pat
- Venue
- Nature Neuroscience
- Published
- 2011-10-30
- Volume
- 14
- Issue
- 12
- Pages
- 1499-1506
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3940335
- OpenAlex
- W2073154969
- Cited by
- 306
- References
- 86
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 7 · 2023: 6 · 2022: 11 · 2021: 19 · 2020: 10 · 2019: 13 · 2018: 13 · 2017: 17 · 2016: 30 · 2015: 27 · 2014: 46 · 2013: 48 · 2012: 47
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (RC2MH089956, MH089956, R01MH080759, MH067842, MH081754, R01MH081754, R01MH067842, R56MH067842, MH080759)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- autism spectrum disorder, genetic risk, gene discovery, mental illness, neurodevelopmental disorders
- MeSH terms
- Child, Child Development Disorders, Pervasive, Humans, Nerve Tissue Proteins, Risk Factors, Genetic Variation, Genetic Predisposition to Disease
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
