Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder
Abstract
A universal challenge in genetic studies of autism spectrum disorders (ASDs) is determining whether a given DNA sequence alteration will manifest as disease. Among different population controls, we observed, for specific exons, an inverse correlation between exon expression level in brain and burden of rare missense mutations. For genes that harbor de novo mutations predicted to be deleterious, we found that specific critical exons were significantly enriched in individuals with ASD relative to their siblings without ASD (P < 1.13 × 10(-38); odds ratio (OR) = 2.40). Furthermore, our analysis of genes with high exonic expression in brain and low burden of rare mutations demonstrated enrichment for known ASD-associated genes (P < 3.40 × 10(-11); OR = 6.08) and ASD-relevant fragile-X protein targets (P < 2.91 × 10(-157); OR = 9.52). Our results suggest that brain-expressed exons under purifying selection should be prioritized in genotype-phenotype studies for ASD and related neurodevelopmental conditions.
Integrity signals
Registry
Cites
Statistics
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?
Brain-critical exons have high gene expression in brain and low rare burden of rare mutations, and have been proposed to represent autism candidate genes.
“which have high gene expression in brain and low rare burden of rare mutations, and have been proposed to represent autism candidate genes25”
From Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism (2014) · cites this paper as [25]
Uddin et al. identified 3,955 exons mapping to 1,744 genes with high expression in the brain and a low burden of rare mutations, designated as 'brain-critical exons'.
“Finally, Uddin et al. identified 3,955 exons mapping to 1,744 genes with high expression in the brain and a low burden of rare mutations, and designate these as ‘brain-critical exons’25.”
From Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism (2014) · cites this paper as [25]
Many of the genes associated with ASD are also linked with elemental homeostasis, and genes implicated in ASD converge to specific neuronal co-expression networks especially during the same critical early developmental periods observed in this study.
“Notably, many of the genes associated with ASD are also linked with elemental homeostasis930, and it is intriguing that genes implicated in ASD converge to specific neuronal co-expression networks especially during the same critical early developmental periods we have observed in this study313233.”
From Fetal and postnatal metal dysregulation in autism (2017) · cites this paper as [31]
Cites
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · see citing works
Spatio-temporal transcriptome of the human brain
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A. M. M., Pletikos, M., Meyer, K. A., Sedmak, G., et al. (2011) · Nature · doi:10.1038/nature10523 · Cited by 2,084 · see citing works
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084 · see citing works
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · 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 · cited 1× · see citing works
“As a negative control, we analyzed an equal number of exons (3,955) that are enriched for rare missense mutations and are highly expressed in the brain.”
BackgroundSelf-citationTranscriptomic 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
Self-citationStructural 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
Self-citationPatterns and rates of exonic de novo mutations in autism spectrum disorders
Neale, B. M., Kou, Y., Liu, L., Ma’ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., et al. (2012) · Nature · doi:10.1038/nature11011 · Cited by 1,734 · see citing works
Evolution and functional impact of rare coding variation from deep sequencing of human exomes
Tennessen, J. A., Bigham, A. W., O’Connor, T. D., Fu, W., Kenny, E. E., Gravel, S., McGee, S., Do, R., Liu, X., Jun, G., et al. (2012) · Science · doi:10.1126/science.1219240 · Cited by 1,613 · see citing works
De Novo Gene Disruptions in Children on the Autistic Spectrum
Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., Yamrom, B., Lee, Y.-H., Narzisi, G., Leotta, A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.04.009 · Cited by 1,446 · see citing works
Self-citationAnalysis and design of RNA sequencing experiments for identifying isoform regulation
Katz, Y., Wang, E. T., Airoldi, E. M., & Burge, C. B. (2010) · Nature Methods · doi:10.1038/nmeth.1528 · Cited by 1,353 · see citing works
A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes
MacArthur, D. G., Balasubramanian, S., Frankish, A., Huang, N., Morris, J., Walter, K., Jostins, L., Habegger, L., Pickrell, J. K., Montgomery, S. B., et al. (2012) · Science · doi:10.1126/science.1215040 · Cited by 1,272 · 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
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., MacKenzie, A. P., Ng, S. B., Baker, C., et al. (2011) · Nature Genetics · doi:10.1038/ng.835 · Cited by 1,203 · see citing works
Rauch, A., Wieczorek, D., Graf, E., Wieland, T., Endele, S., Schwarzmayr, T., Albrecht, B., Bartholdi, D., Beygo, J., Di Donato, N., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61480-9 · Cited by 1,041 · see citing works
Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism
Parikshak, N. N., Luo, R., Zhang, A., Won, H., Lowe, J. K., Chandran, V., Horvath, S., & Geschwind, D. H. (2013) · Cell · doi:10.1016/j.cell.2013.10.031 · Cited by 1,039 · see citing works
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders
Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., Thiruvahindrapuram, B., Xu, X., Ziman, R., Wang, Z., et al. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.03.018 · Cited by 969 · see citing works
Self-citationBetancur, C. (2011) · Brain Research · doi:10.1016/j.brainres.2010.11.078 · Cited by 954 · see citing works
Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants
Fu, W., O’Connor, T. D., Jun, G., Kang, H. M., Abecasis, G. R., Leal, S. M., Gabriel, S., Rieder, M. J., Altshuler, D., Shendure, J., et al. (2012) · Nature · doi:10.1038/nature11690 · Cited by 951 · 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
Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes
Petrovski, S., Wang, Q., Heinzen, E. L., Allen, A. S., & Goldstein, D. B. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003709 · Cited by 901 · see citing works
Barash, Y., Calarco, J. A., Gao, W., Pan, Q., Wang, X., Ofer Shai, A., Blencowe, B. J., & Frey, B. J. (2010) · Nature · doi:10.1038/nature09000 · Cited by 891 · see citing works
Self-citationA de novo paradigm for mental retardation.
Vissers, L. E. L. M., de Ligt, J., Gilissen, C., Janssen, I., Steehouwer, M., de Vries, P., van Lier, B., Arts, P., Wieskamp, N., del Rosario, M., et al. (2010) · Nature Genetics · doi:10.1038/ng.712 · Cited by 852 · 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
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
Self-citationGulsuner, S., Walsh, T., Watts, A. C., Lee, M. K., Thornton, A. M., Casadei, S., Rippey, C., Shahin, H., Braff, D., Cadenhead, K. S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.049 · Cited by 536 · see citing works
Characterization of the proteome, diseases and evolution of the human postsynaptic density
Bayés, À., van de Lagemaat, L. N., Collins, M. O., Croning, M. D. R., Whittle, I. R., Choudhary, J. S., & Grant, S. G. N. (2011) · Nature Neuroscience · doi:10.1038/nn.2719 · Cited by 499 · see citing works
Jiang, Y.-H., Yuen, R. K. C., Jin, X., Wang, M., Chen, N., Wu, X., Ju, J., Mei, J., Shi, Y., He, M., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.06.012 · Cited by 474 · see citing works
Self-citationExome sequencing supports a de novo mutational paradigm for schizophrenia
Xu, B., Roos, J. L., Dexheimer, P. J., Boone, B. E., Plummer, B., Levy, S., Gogos, J. A., & Karayiorgou, M. (2011) · Nature Genetics · doi:10.1038/ng.902 · Cited by 465 · see citing works
Individual common variants exert weak effects on the risk for autism spectrum disorders
Anney, R., Klei, L., Pinto, D., Almeida, J., Bacchelli, E., Baird, G., Bolshakova, N., Bölte, S., Bolton, P. F., Bourgeron, T., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds301 · Cited by 375 · see citing works
Self-citationIntegrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics
Khurana, E., Fu, Y., Colonna, V., Mu, X. J., Kang, H. M., Lappalainen, T., Sboner, A., Lochovsky, L., Chen, J., Harmanci, A. O., et al. (2013) · Science · doi:10.1126/science.1235587 · Cited by 359 · see citing works
Gardina, P. J., Clark, T. A., Shimada, B., Staples, M. K., Yang, Q., Veitch, J. M., Schweitzer, A. C., Awad, T. A., Sugnet, C. W., Dee, S., et al. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-325 · Cited by 352 · see citing works
Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder
Vaags, A. K., Lionel, A. C., Sato, D., Goodenberger, M. L., Stein, Q., Curran, S. R., Ogilvie, C. M., Ahn, J. W., Drmic, I., Senman, L., et al. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.025 · Cited by 205 · see citing works
Self-citationBeunders, G., Voorhoeve, E., Golzio, C., Pardo, L. M., Rosenfeld, J. A., Talkowski, M. E., Simonic, I., Lionel, A. C., Vergult, S., Pyatt, R. E., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.12.011 · Cited by 185 · see citing works
Self-citationLionel, A. C., Tammimies, K., Vaags, A. K., Rosenfeld, J. A., Ahn, J. W., Merico, D., Noor, A., Runke, C. K., Pillalamarri, V. K., Carter, M. T., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt669 · Cited by 163 · see citing works
Self-citationFOXP2 Targets Show Evidence of Positive Selection in European Populations
Ayub, Q., Yngvadóttir, B., Chen, Y., Xue, Y., Hu, M., Vernes, S. C., Fisher, S. E., & Tyler‐Smith, C. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.03.019 · Cited by 78 · 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
Narrowing the critical deletion region for autism spectrum disorders on 16p11.2
Crepel, A., Steyaert, J. G., la Marche, W. D., Wolf, V. D., Fryns, J., Noens, I. L. J., Devriendt, K., & Peeters, H. (2011) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31163 · Cited by 61 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The human splicing code reveals new insights into the genetic determinants of disease
Xiong, H. Y., Alipanahi, B., Lee, L. J., Bretschneider, H., Merico, D., Yuen, R. K. C., Hua, Y., Gueroussov, S., Najafabadi, H. S., Hughes, T., et al. (2014) · Science · doi:10.1126/science.1254806 · Cited by 1,225 · see citing works
Self-citationFrom the genetic architecture to synaptic plasticity in autism spectrum disorder
Bourgeron, T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3992 · Cited by 975 · see citing works
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
C Yuen, R. K., Merico, D., Bookman, M., L Howe, J., Thiruvahindrapuram, B., Patel, R. V., Whitney, J., Deflaux, N., Bingham, J., Wang, Z., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4524 · Cited by 844 · see citing works
Self-citationA copy number variation map of the human genome
Zarrei, M., MacDonald, J. R., Merico, D., & Scherer, S. W. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3871 · Cited by 921 · see citing works
Self-citationWhole-genome sequencing of quartet families with autism spectrum disorder
Yuen, R. K. C., Thiruvahindrapuram, B., Merico, D., Walker, S., Tammimies, K., Hoang, N., Chrysler, C., Nalpathamkalam, T., Pellecchia, G., Liu, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3792 · Cited by 514 · see citing works
Self-citationGupta, S., Ellis, S. E., Ashar, F. N., Moes, A., Bader, J. S., Zhan, J., West, A. B., & Arking, D. E. (2014) · Nature Communications · doi:10.1038/ncomms6748 · Cited by 504 · see citing works
“However, we do find modest enrichment for a broader set of genes containing ‘brain-critical exons’, which have high gene expression in brain and low rare burden of rare mutations, and have been proposed to represent autism candidate genes 25 (Supplementary Data 8a).”
The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders
Smoller, J. W. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.266 · Cited by 479 · see citing works
Krishnan, A., Zhang, R., Yao, V., Theesfeld, C. L., Wong, A. K., Tadych, A., Volfovsky, N., Packer, A. I., Lash, A., & Troyanskaya, O. G. (2016) · Nature Neuroscience · doi:10.1038/nn.4353 · Cited by 427 · see citing works
Tammimies, K., Marshall, C. R., Walker, S., Kaur, G., Thiruvahindrapuram, B., Lionel, A. C., Yuen, R. K. C., Uddin, M., Roberts, W., Weksberg, R., et al. (2015) · JAMA · doi:10.1001/jama.2015.10078 · Cited by 419 · see citing works
Self-citationRates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder
Lim, E. T., Uddin, M., De Rubeis, S., Chan, Y., Kamumbu, A. S., Zhang, X., D'Gama, A. M., Kim, S. N., Hill, R. S., Goldberg, A. P., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4598 · Cited by 299 · see citing works
Self-citationExome sequencing of 457 autism families recruited online provides evidence for autism risk genes
Feliciano, P., Zhou, X., Astrovskaya, I., Turner, T. N., Wang, T., Brueggeman, L., Barnard, R., Hsieh, A., Snyder, L. G., Muzny, D. M., et al. (2019) · npj Genomic Medicine · doi:10.1038/s41525-019-0093-8 · Cited by 247 · see citing works
Artificial intelligence for precision medicine in neurodevelopmental disorders
Uddin, M. J., Wang, Y., & Woodbury‐Smith, M. (2019) · npj Digital Medicine · doi:10.1038/s41746-019-0191-0 · Cited by 257 · see citing works
Self-citationA deep learning model for the detection of both advanced and early glaucoma using fundus photography
Ahn, J. M., Kim, S., Ahn, K.-S., Cho, S., Lee, K. B., & Kim, U. S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0207982 · Cited by 248 · see citing works
Genome-wide characteristics of de novo mutations in autism
Yuen, R. K., Merico, D., Cao, H., Pellecchia, G., Alipanahi, B., Thiruvahindrapuram, B., Tong, X., Sun, Y., Cao, D., Zhang, T., et al. (2016) · npj Genomic Medicine · doi:10.1038/npjgenmed.2016.27 · Cited by 216 · see citing works
Self-citationGenomics, convergent neuroscience and progress in understanding autism spectrum disorder
Willsey, H. R., Willsey, A. J., Wang, B., & State, M. W. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00576-7 · Cited by 229 · see citing works
Sahu, M., Gupta, R. V., Ambasta, R. K., & Kumar, P. (2022) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2022.03.002 · Cited by 202 · see citing works
Aggarwala, V., & Voight, B. F. (2016) · Nature Genetics · doi:10.1038/ng.3511 · Cited by 181 · see citing works
Genetic contributions to autism spectrum disorder
Havdahl, A., Niarchou, M., Starnawska, A., Uddin, M., van der Merwe, C., & Warrier, V. (2021) · Psychological Medicine · doi:10.1017/s0033291721000192 · Cited by 193 · see citing works
Self-citationFetal and postnatal metal dysregulation in autism
Arora, M., Reichenberg, A., Willfors, C., Austin, C., Gennings, C., Berggren, S., Lichtenstein, P., Anckarsäter, H., Tammimies, K., & Bölte, S. (2017) · Nature Communications · doi:10.1038/ncomms15493 · Cited by 169 · see citing works
Self-citationAutism spectrum disorders: from genes to neurobiology
Jeremy Willsey, A., & State, M. W. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.10.015 · Cited by 145 · see citing works
Sestan, N., & State, M. W. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.015 · Cited by 127 · see citing works
Chen, C., Meng, Q., Xia, Y., Ding, C., Wang, L., Dai, R., Cheng, L., Gunaratne, P. H., Gibbs, R. A., Min, S., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat8178 · Cited by 107 · see citing works
Sex Biased Gene Expression Profiling of Human Brains at Major Developmental Stages
Shi, L., Zhang, Z., & Su, B. (2016) · Scientific Reports · doi:10.1038/srep21181 · Cited by 109 · see citing works
Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish
Kozol, R. A., Abrams, A. J., James, D. M., Buglo, E., Yan, Q., & Dallman, J. E. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00055 · Cited by 108 · see citing works
OTUD7A Regulates Neurodevelopmental Phenotypes in the 15q13.3 Microdeletion Syndrome
Uddin, M. J., Unda, B. K., Kwan, V., Holzapfel, N. T., White, S. H., Chalil, L., Woodbury‐Smith, M., Ho, K. S., Harward, E., Murtaza, N., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.01.006 · Cited by 104 · see citing works
Self-citationLi, J., Wilkinson, B., Clementel, V. A., Hou, J., O’Dell, T. J., & Coba, M. P. (2016) · Science Signaling · doi:10.1126/scisignal.aaf6716 · Cited by 95 · see citing works
De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy
Zarrei, M., Fehlings, D. L., Mawjee, K., Switzer, L., Thiruvahindrapuram, B., Walker, S., Merico, D., Casallo, G., Uddin, M. J., MacDonald, J. R., et al. (2017) · Genetics in Medicine · doi:10.1038/gim.2017.83 · Cited by 99 · see citing works
Self-citationLal, D., Ruppert, A., Trucks, H., Schulz, H., de Kovel, C. G. F., Trenité, D. G. A. K.-N., Sonsma, A. C. M., Koeleman, B. P. C., Lindhout, D., Weber, Y. G., et al. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005226 · Cited by 97 · see citing works
Lowther, C., Speevak, M. D., Armour, C. M., Goh, E. S., Graham, G. E., Li, C. C., Zeesman, S., Nowaczyk, M. J. M., Schultz, L., Morra, A., et al. (2016) · Genetics in Medicine · doi:10.1038/gim.2016.54 · Cited by 91 · see citing works
Self-citationDeneault, É., Faheem, M., White, S. H., Rodrigues, D. C., Sun, S., Wei, W., Piekna, A., Thompson, T., Howe, J., Chalil, L., et al. (2019) · eLife · doi:10.7554/elife.40092 · Cited by 96 · see citing works
Self-citationCoexpression networks identify brain region–specific enhancer RNAs in the human brain
Yao, P., Lin, P., Gokoolparsadh, A., Assareh, A. A., Thang, M. W. C., & Voineagu, I. (2015) · Nature Neuroscience · doi:10.1038/nn.4063 · Cited by 91 · see citing works
The Genetics of Autism Spectrum Disorders
Huguet, G., Benabou, M., & Bourgeron, T. (2016) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-319-27069-2_11 · Cited by 94 · see citing works
Nguyen, H. T., Bryois, J., Kim, A., Dobbyn, A. L., Huckins, L. M., Muñoz‐Manchado, A. B., Ruderfer, D. M., Genovese, G., Fromer, M., Xu, X., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0497-y · Cited by 86 · see citing works
Self-citationPhenotypic effects of genetic variants associated with autism
Rolland, T., Cliquet, F., Anney, R., Moreau, C. A., Traut, N., Mathieu, A., Huguet, G., Duan, J., Warrier, V., Portalier, S., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02408-2 · Cited by 82 · see citing works
A high-resolution copy-number variation resource for clinical and population genetics
Uddin, M. J., Thiruvahindrapuram, B., Walker, S., Wang, Z., Hu, P., Lamoureux, S., Wei, J., MacDonald, J. R., Pellecchia, G., Lu, C., et al. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.178 · Cited by 79 · see citing works
Self-citationBeversdorf, D. Q., & MISSOURI AUTISM SUMMIT CONSORTIUM* (2016) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0000000000000351 · Cited by 74 · see citing works
Gazzellone, M. J., Zarrei, M., Burton, C. L., Walker, S., Uddin, M., Shaheen, S. M., Coste, J., Rajendram, R., Schachter, R. J., Colasanto, M., et al. (2016) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-016-9170-9 · Cited by 77 · see citing works
Self-citationRecent Advances in the Genetics of Autism Spectrum Disorder
Rubeis, S. D., & Buxbaum, J. D. (2015) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0553-1 · Cited by 75 · see citing works
TBR1 regulates autism risk genes in the developing neocortex
Notwell, J. H., Heavner, W. E., Darbandi, S. F., Katzman, S., McKenna, W. L., Ortiz-Londono, C. F., Tastad, D., Eckler, M. J., Rubenstein, J. L. R., McConnell, S. K., et al. (2016) · Genome Research · doi:10.1101/gr.203612.115 · Cited by 74 · see citing works
Butler, M. G., Rafi, S. K., & Manzardo, A. M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16036464 · Cited by 73 · see citing works
Nguyen, R. L., Medvedeva, Y. V., Ayyagari, T., Schmunk, G., & Gargus, J. J. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.08.003 · Cited by 70 · see citing works
MTSplice predicts effects of genetic variants on tissue-specific splicing
Cheng, J., Çelik, M. H., Kundaje, A. B., & Gagneur, J. (2021) · Genome biology · doi:10.1186/s13059-021-02273-7 · Cited by 66 · see citing works
Genetic heterogeneity in autism: From single gene to a pathway perspective
An, J., & Claudianos, C. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.013 · Cited by 64 · see citing works
Germline and somatic mutations in <i>STXBP1</i> with diverse neurodevelopmental phenotypes
Uddin, M., Woodbury-Smith, M., Chan, A., Brunga, L., Lamoureux, S., Pellecchia, G., Yuen, R. K. C., Faheem, M., Stavropoulos, D. J., Drake, J., et al. (2017) · Neurology Genetics · doi:10.1212/nxg.0000000000000199 · Cited by 57 · see citing works
Self-citationDe novo Mutations (DNMs) in Autism Spectrum Disorder (ASD): Pathway and Network Analysis
Alonso-González, A., Rodriguez‐Fontenla, C., & Carracedo, Á. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00406 · Cited by 65 · see citing works
Ilan, Y. (2020) · Frontiers in Digital Health · doi:10.3389/fdgth.2020.569178 · Cited by 63 · see citing works
Copy number variation in Han Chinese individuals with autism spectrum disorder
Gazzellone, M. J., Zhou, X., Lionel, A. C., Uddin, M. J., Thiruvahindrapuram, B., Liang, S., Sun, C., Wang, J., Zou, M., Tammimies, K., et al. (2014) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-6-34 · Cited by 58 · see citing works
Self-citationWong, A. H. C., & Josselyn, S. A. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.04.023 · Cited by 55 · see citing works
Ge, X., Gong, H. Z., Dumas, K., Litwin, J., Phillips, J. J., Waisfisz, Q., Weiss, M. M., Hendriks, Y. M. C., Stuurman, K. E., Nelson, S. F., et al. (2016) · npj Genomic Medicine · doi:10.1038/npjgenmed.2016.36 · Cited by 54 · see citing works
Kalueff, A. V., Stewart, A., Song, C., & Gottesman, I. I. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.03.007 · Cited by 50 · see citing works
Functional Connectome–Based Predictive Modeling in Autism
Horien, C. L., Floris, D. L., Greene, A. S., Noble, S., Rolison, M. J., Tejavibulya, L., O’Connor, D. A., McPartland, J. C., Scheinost, D., Chawarska, K., et al. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.04.008 · Cited by 47 · see citing works
Rao, S., Baranova, A. V., Yao, Y., Wang, J., & Zhang, F. (2022) · Neuropsychobiology · doi:10.1159/000525411 · Cited by 50 · see citing works
Wang, Q., Li, M., Yang, Z., Hu, X., Wu, H.-M., Ni, P., Ren, H., Deng, W., Li, M., Ma, X., et al. (2015) · Scientific Reports · doi:10.1038/srep18209 · Cited by 48 · see citing works
Automated analysis of retinal imaging using machine learning techniques for computer vision
Fauw, J. D., Keane, P. A., Tomašev, N., Visentin, D., van den Driessche, G., Johnson, M., Hughes, C., Chu, C., Ledsam, J. R. E., Back, T., et al. (2016) · F1000Research · doi:10.12688/f1000research.8996.1 · Cited by 48 · see citing works
Tindi, J. O., Chávez, A. E., Cvejic, S., Calvo‐Ochoa, E., Castillo, P. E., & Jordan, B. A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4029-14.2015 · Cited by 45 · see citing works
Gardoni, F., & Luca, M. D. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108551 · Cited by 42 · see citing works
Schmunk, G., Nguyen, R. L., Ferguson, D. L., Kumar, K., Parker, I., & Gargus, J. J. (2017) · Scientific Reports · doi:10.1038/srep40740 · Cited by 44 · see citing works
Chau, K. K., Zhang, P., Urresti, J., Amar, M., Pramod, A. B., Chen, J., Thomas, A. E., Corominas, R., Lin, G. N., & Iakoucheva, L. M. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109631 · Cited by 42 · see citing works
Indexing Effects of Copy Number Variation on Genes Involved in Developmental Delay
Uddin, M. J., Pellecchia, G., Thiruvahindrapuram, B., D’Abate, L., Merico, D., Chan, A. J. S., Zarrei, M., Tammimies, K., Walker, S., Gazzellone, M. J., et al. (2016) · Scientific Reports · doi:10.1038/srep28663 · Cited by 42 · see citing works
Self-citationZarrei, M., Merico, D., Kellam, B., Engchuan, W., Scriver, T., Jokhan, R., Wilson, M. D., Parr, J. R., Lemire, E. G., Stavropoulos, D. J., et al. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38176 · Cited by 41 · see citing works
Self-citationSynapse-to-nucleus communication: from developmental disorders to Alzheimer's disease
Marcello, E. E., Luca, M. D., & Gardoni, F. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.12.017 · Cited by 41 · see citing works
Begum, G., Albanna, A., Bankapur, A., Nassir, N., Tambi, R., Berdiev, B. K., Akter, H., Karuvantevida, N. S., Kellam, B., Alhashmi, D., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042060 · Cited by 39 · see citing works
Self-citationNassir, N., Bankapur, A., Samara, B., Ali, A. Y., Ahmed, A., Inuwa, I. M., Zarrei, M., Shabestari, S. A. S., Albanna, A., Howe, J., et al. (2021) · Human Genomics · doi:10.1186/s40246-021-00368-7 · Cited by 38 · see citing works
Self-citationLiu, Y., Zhao, D., Dong, R., Yang, X., Zhang, Y., Tammimies, K., Uddin, M. J., Scherer, S. W., & Gai, Z. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37050 · Cited by 37 · see citing works
Self-citationRiggs, E. R., Nelson, T. H., Merz, A., Ackley, T., Bunke, B. P., Collins, C. D., Collinson, M. N., Fan, Y., Goodenberger, M. L., Golden, D. M., et al. (2018) · Human Mutation · doi:10.1002/humu.23610 · Cited by 38 · see citing works
Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome
Carbonell, A. U., Cho, C. H., Tindi, J. O., Counts, P. A., Bates, J. C., Erdjument‐Bromage, H., Cvejic, S., Iaboni, A., Kvint, I., Rosensaft, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11437-w · Cited by 38 · see citing works
Self-citationEvoTol: a protein-sequence based evolutionary intolerance framework for disease-gene prioritization
Rackham, O. J. L., Shihab, H. A., Johnson, M. R., & Petretto, E. G. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1322 · Cited by 36 · see citing works
Rare and de novo coding variants in chromodomain genes in Chiari I malformation
Sadler, B. E., Wilborn, J., Antunes, L., Kuensting, T., Hale, A. T., Gannon, S. R., McCall, K., Cruchaga, C., Harms, M. B., Voisin, N., et al. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.12.001 · Cited by 35 · see citing works
Liu, Y., Zhang, Y., Zhao, D., Dong, R., Yang, X., Tammimies, K., Uddin, M. J., Scherer, S. W., & Gai, Z. (2015) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32306 · Cited by 34 · see citing works
Self-citationAutism throughout genetics: Perusal of the implication of ion channels
Daghsni, M., Rima, M., Fajloun, Z., Ronjat, M., Brusés, J. L., Mrad, R., & WAARD, M. M. D. (2018) · Brain and Behavior · doi:10.1002/brb3.978 · Cited by 33 · see citing works
Parent-of-Origin Effects in 15q11.2 BP1-BP2 Microdeletion (Burnside-Butler) Syndrome
Davis, K., Serrano, M. A., Loddo, S., Robinson, C., Alesi, V., Dallapiccola, B., Novelli, A., & Butler, M. G. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061459 · Cited by 32 · see citing works
Kizner, V., Naujock, M., Fischer, S. E., Jäger, S., Reich, S., Schlotthauer, I., Zuckschwerdt, K., Geiger, T., Hildebrandt, T., Lawless, N., et al. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01727-1 · Cited by 31 · see citing works
Ouwenga, R., & Dougherty, J. D. (2015) · Molecular Autism · doi:10.1186/s13229-015-0008-1 · Cited by 31 · see citing works
Yuan, F.-F., Gu, X., Huang, X., Zhong, Y., & Wu, J. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.04.015 · Cited by 29 · see citing works
Pérez‐Palma, E., Helbig, I., Klein, K. M., Anttila, V., Horn, H., Reinthaler, E. M., Gormley, P., Ganna, A., Byrnes, A., Pernhorst, K., et al. (2017) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2016-104495 · Cited by 26 · see citing works
Brain transcriptome atlases: a computational perspective
Mahfouz, A. E., Huisman, S. M. H., Lelieveldt, B. P. F., & Reinders, M. J. T. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1338-2 · Cited by 26 · see citing works
Cross-Disorder Comparison of Four Neuropsychiatric CNV Loci
Moreno‐De‐Luca, D., Moreno-De-Luca, A., Cubells, J. F., & Sanders, S. (2014) · Current Genetic Medicine Reports · doi:10.1007/s40142-014-0045-7 · Cited by 24 · see citing works
Uddin, M. J., Codner, D., Hasan, S. M. M., Scherer, S. W., O’Rielly, D. D., & Rahman, P. (2015) · Scientific Reports · doi:10.1038/srep10314 · Cited by 25 · see citing works
Self-citationAssociation of IMMP2L deletions with autism spectrum disorder: A trio family study and meta‐analysis
Zhang, Y., Liu, Y., Zarrei, M., Tong, W. W. L., Dong, R., Wang, Y., Zhang, H., Yang, X., MacDonald, J. R., Uddin, M. J., et al. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32608 · Cited by 24 · see citing works
Self-citationUsing extended pedigrees to identify novel autism spectrum disorder (ASD) candidate genes
Woodbury‐Smith, M., Paterson, A. D., Thiruvahindrapduram, B., Lionel, A. C., Marshall, C. R., Merico, D., Fernandez, B. A., Duku, E., Sutcliffe, J. S., O’Conner, I., et al. (2014) · Human Genetics · doi:10.1007/s00439-014-1513-6 · Cited by 22 · see citing works
Self-citationVorstman, J. A. S., & Scherer, S. W. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.12.017 · Cited by 19 · see citing works
Self-citationShabestari, S. A. S., Nassir, N., Sopariwala, S., Karimov, I., Tambi, R., Zehra, B., Kosaji, N., Akter, H., Berdiev, B. K., & Uddin, M. J. (2022) · Human Genetics · doi:10.1007/s00439-022-02482-5 · Cited by 21 · see citing works
Self-citationPSYCHIATRIC GENETICS AND THE FUTURE OF PERSONALIZED TREATMENT
Smoller, J. W. (2014) · Depression and Anxiety · doi:10.1002/da.22322 · Cited by 21 · see citing works
Vanzo, R. J., Twede, H., Ho, K. S., Prasad, A., Martin, M. M., South, S. T., & Wassman, E. R. (2018) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2018.04.012 · Cited by 21 · see citing works
Automated analysis of retinal imaging using machine learning techniques for computer vision
Fauw, J. D., Keane, P. A., Tomašev, N., Visentin, D., van den Driessche, G., Johnson, M., Hughes, C., Chu, C., Ledsam, J. R. E., Back, T., et al. (2017) · F1000Research · doi:10.12688/f1000research.8996.2 · Cited by 18 · see citing works
Colvin, S. M., & Kwan, K. Y. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00239 · Cited by 17 · see citing works
Beversdorf, D. Q., Anagnostou, E. A., Hardan, A. Y., Wang, P. P., Erickson, C. A., Frazier, T. W., & Veenstra-VanderWeele, J. M. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1079006 · Cited by 19 · see citing works
Khan, A., Liu, Q., & Wang, K. (2018) · BMC Bioinformatics · doi:10.1186/s12859-018-2469-7 · Cited by 16 · see citing works
Akter, H., Hossain, M. S., Dity, N. J., Rahaman, A., Uddin, K. M. F., Nassir, N., Begum, G., Hameid, R. A., Islam, M. S., Tusty, T. A., et al. (2021) · npj Genomic Medicine · doi:10.1038/s41525-021-00173-0 · Cited by 16 · see citing works
Self-citationGenetic Causes of Autism Spectrum Disorders
Huguet, G., & Bourgeron, T. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800109-7.00002-9 · Cited by 16 · see citing works
Uddin, K. M. F., Amin, M. R., Majumder, S. N., Aleem, M. A., Rahaman, A., Dity, N. J., Baqui, M. A., Akter, H., Rahman, M. M., Woodbury‐Smith, M., et al. (2018) · Clinical Case Reports · doi:10.1002/ccr3.1595 · Cited by 16 · see citing works
Self-citationRahman, M. M., Uddin, K. M. F., Al‐Jezawi, N. K., Karuvantevida, N. S., Akter, H., Dity, N. J., Rahaman, M. A., Begum, M., Rahaman, A., Baqui, M. A., et al. (2019) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.954 · Cited by 16 · see citing works
Self-citationAkter, H., Rahman, M. M., Sarker, S., Basiruzzaman, M., Islam, M. M., Rahaman, A., Rahaman, M. A., Eshaque, T. B., Dity, N. J., Sarker, S., et al. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.955631 · Cited by 15 · see citing works
Self-citationRare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders
Costain, G., Walker, S., Argiropoulos, B., Baribeau, D. A., Bassett, A. S., Boot, E., Devriendt, K., Kellam, B., Marshall, C. R., Prasad, A., et al. (2019) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-019-9263-3 · Cited by 15 · see citing works
Self-citationA genomic view on epilepsy and autism candidate genes
Jabbari, K., & Nürnberg, P. (2016) · Genomics · doi:10.1016/j.ygeno.2016.01.001 · Cited by 14 · see citing works
Anatomy and Cell Biology of Autism Spectrum Disorder: Lessons from Human Genetics
Kleijer, K. T. E., Huguet, G., Tastet, J., Bourgeron, T., & Burbach, J. P. H. (2017) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-319-52498-6_1 · Cited by 13 · see citing works
Bassani, S., van Beelen, E. S. A., Rossel, M., Voisin, N., Morgan, A., Arribat, Y., Chatron, N., Chrast, J., Cocca, M., Delprat, B., et al. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab145 · Cited by 12 · see citing works
Mapping human brain cell type origin and diseases through single-cell transcriptomics
Soorajkumar, A., Balan, B., Nassir, N., Akter, H., Shahin, Z., Berdiev, B. K., Woodbury‐Smith, M., Khalil, R., Cisse, B., Benamer, H. T. S., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03562-6 · Cited by 13 · see citing works
Self-citationRanieri, A., Monica, I. L., Iorio, M. R. D., Lombardo, B., & Pastore, L. (2024) · Genes · doi:10.3390/genes15040427 · Cited by 11 · see citing works
Hensel, C. H., Vanzo, R. J., Martin, M. M., Dixon, S., Lambert, C. G., Levy, B., Nelson, L. M., Peiffer, A. P., Ho, K. S., Rushton, P., et al. (2017) · PLoS Currents · doi:10.1371/currents.eogt.7d92ce775800ef3fbc72e3840fb1bc22 · Cited by 11 · see citing works
- Authors
- Uddin, M., Tammimies, K., Pellecchia, G., Alipanahi, B., Hu, P., Wang, Z., Pinto, D., Lau, L., Nalpathamkalam, T., Marshall, C. R., Blencowe, B. J., Frey, B. J., Merico, D., Yuen, R. K. C., & Scherer, S. W.
- Affiliations
- Hospital for Sick Children (CA)
- University of Toronto (CA)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Scherer, Stephen W
- ORCID
- Venue
- Nature Genetics
- Published
- 2014-05-25
- Volume
- 46
- Issue
- 7
- Pages
- 742-747
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2055068525
- Cited by
- 163
- References
- 38
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 7 · 2022: 13 · 2021: 12 · 2020: 8 · 2019: 11 · 2018: 19 · 2017: 18 · 2016: 27 · 2015: 21 · 2014: 10
- FWCI
- 14.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (FRNXGG818, FRN 74527)
- 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 › Genomics and Rare Diseases
- Keywords
- autism spectrum disorder, de novo mutations, purifying selection, genotype-phenotype correlation, neurodevelopmental disorders
- MeSH terms
- Adolescent, Adult, Brain, Child Development Disorders, Pervasive, Child, Preschool, Exons, Female, Humans, Infant, Male, Phenotype, RNA, Messenger, Case-Control Studies, Genetic Predisposition to Disease, Mutation, Missense, Reverse Transcriptase Polymerase Chain Reaction, Gene Regulatory Networks, Real-Time Polymerase Chain Reaction
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
