The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model
Open accessAbstract
Background: We previously performed targeted sequencing of autism risk genes in probands from the Autism Clinical and Genetic Resources in China (ACGC) (phase I). Here, we expand this analysis to a larger cohort of patients (ACGC phase II) to better understand the prevalence, inheritance, and genotype-phenotype correlations of likely gene-disrupting (LGD) mutations for autism candidate genes originally identified in cohorts of European descent. Methods: We sequenced 187 autism candidate genes in an additional 784 probands and 85 genes in 599 probands using single-molecule molecular inversion probes. We tested the inheritance of potentially pathogenic mutations, performed a meta-analysis of phase I and phase II data and combined our results with existing exome sequence data to investigate the phenotypes of carrier parents and patients with multiple hits in different autism risk genes. Results: ). We identified the transmission of private LGD mutations in genes predominantly associated with DNMs and showed that parental carriers tended to share milder autism-related phenotypes. Patients that carried DNMs in two or more candidate genes show more severe phenotypes. Conclusions: We identify new risk genes and transmission of deleterious mutations in genes primarily associated with DNMs. The fact that parental carriers show milder phenotypes and patients with multiple hits are more severe supports a multifactorial model of risk.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For example, Guo et al. 25 assessed three families in which likely gene-disrupting CHD8 mutations were transmitted from parents with full-scale IQ scores between 80 and 87 (verbal IQ 88–-95, nonverbal IQ 75–79), establishing the possibility of relative sparing of cognition.”
From Insufficient Evidence for “Autism-Specific” Genes (2020) · cites this paper as [25]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Self-citation(1943) · The Nervous child · Cited by 8,870
Synaptic, transcriptional and chromatin genes disrupted in autism
Study, T. D., De Rubeis, S., Autism, H. M. C. F., UK10K Consortium, The Autism Sequencing Consortium, He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Ercument Cicek, A., et al. (2014) · Nature · doi:10.1038/nature13772 · Cited by 2,746
Global Prevalence of Autism and Other Pervasive Developmental Disorders
Elsabbagh, M., Divan, G., Koh, Y., Kim, Y. S., Kauchali, S., Marcín, C., Montiel‐Nava, C., Patel, V., Paula, C. S., Wang, C., et al. (2012) · Autism Research · doi:10.1002/aur.239 · Cited by 2,636
The contribution of de novo coding mutations to autism spectrum disorder
Iossifov, I., O’Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Witherspoon, K. T., Vives, L., Patterson, K. E., et al. (2014) · Nature · doi:10.1038/nature13908 · Cited by 2,585
Self-citationAutistic disturbances of affective contact.
Kanner, L. (1968) · PubMed · Cited by 2,282
Targeted capture and massively parallel sequencing of 12 human exomes
Ng, S. B., Turner, E. H., Robertson, P. D., Flygare, S. D., Bigham, A. W., Lee, C., Shaffer, T., Wong, M., Bhattacharjee, A., Eichler, E. E., et al. (2009) · Nature · doi:10.1038/nature08250 · Cited by 2,030
Self-citationChristensen, D. L., Baio, J., Braun, K. V. N., Bilder, D., Charles, J., Constantino, J. N., Daniels, J., Durkin, M. S., Fitzgerald, R. T., Kurzius-Spencer, M., et al. (2016) · MMWR. Surveillance Summaries · doi:10.15585/mmwr.ss6503a1 · Cited by 1,964
Diagnostic exome sequencing in persons with severe intellectual disability
de Ligt, J., Willemsen, M. H., van Bon, B. W. M., Kleefstra, T., Yntema, H. G., Kroes, T., Vulto-van Silfhout, A. T., Koolen, D. A., de Vries, P., Gilissen, C., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1206524 · Cited by 1,546
Prevalence of Autism Spectrum Disorders in a Total Population Sample
Kim, Y. S., Leventhal, B. L., Koh, Y.-J., Fombonne, E., Laska, E., Lim, E.-C., Cheon, K.-A., Kim, S.-J., Kim, Y.-K., Lee, H., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10101532 · Cited by 1,524
De novo mutations in epileptic encephalopathies
Epi4K Consortium, & Epilepsy Phenome/Genome Project (2013) · Nature · doi:10.1038/nature12439 · Cited by 1,514
Prevalence and architecture of de novo mutations in developmental disorders
Study, D. D. D. (2017) · Nature · doi:10.1038/nature21062 · Cited by 1,480
Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci
Sanders, S. J., He, X., Willsey, A. J., Ercan-Sencicek, A. G., Samocha, K. E., Cicek, A. E., Murtha, M. T., Bal, V. H., Bishop, S. L., Dong, S., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.016 · Cited by 1,430
Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders
O’Roak, B. J., Vives, L., Fu, W., Egertson, J. D., Stanaway, I. B., Phelps, I. G., Carvill, G., Kumar, A., Lee, C., Ankenman, K., et al. (2012) · Science · doi:10.1126/science.1227764 · Cited by 1,240
Self-citationExome 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
Self-citationA framework for the interpretation of de novo mutation in human disease
Samocha, K. E., Robinson, E. B., Sanders, S. J., Stevens, C., Sabo, A., McGrath, L. M., Kosmicki, J. A., Rehnström, K., Mallick, S., Kirby, A., et al. (2014) · Nature Genetics · doi:10.1038/ng.3050 · Cited by 979
Epidemiology of Autism Spectrum Disorders in Adults in the Community in England
Brugha, T. S., McManus, S., Bankart, J., Scott, F., Purdon, S., Smith, J., Bebbington, P., Jenkins, R., & Meltzer, H. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.38 · Cited by 903
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
Disruptive CHD8 Mutations Define a Subtype of Autism Early in Development
Bernier, R., Golzio, C., Xiong, B., Stessman, H. A., Coe, B. P., Penn, O., Witherspoon, K., Gerdts, J., Baker, C., Vulto-van Silfhout, A. T., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.017 · Cited by 798
Self-citationA recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Girirajan, S., Rosenfeld, J. A., Cooper, G. M., Antonacci, F., Siswara, P., Itsara, A., Vives, L., Walsh, T., McCarthy, S. E., Baker, C., et al. (2010) · Nature Genetics · doi:10.1038/ng.534 · Cited by 667
Self-citationJacquemont, S., Coe, B. P., Hersch, M., Duyzend, M. H., Krumm, N., Bergmann, S., Beckmann, J. S., Rosenfeld, J. A., & Eichler, E. E. (2014) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.02.001 · Cited by 605
Self-citationDe novo genic mutations among a Chinese autism spectrum disorder cohort
Wang, T., Guo, H., Xiong, B., Stessman, H. A. F., Wu, H., Coe, B. P., Turner, T. N., Liu, Y., Zhao, W., Hoekzema, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms13316 · Cited by 369
Self-citationGenetic risk for autism spectrum disorders and neuropsychiatric variation in the general population
iPSYCH-SSI-Broad Autism Group, Robinson, E. B., St Pourcain, B., Anttila, V., Kosmicki, J. A., Bulik-Sullivan, B., Grove, J., Maller, J., Samocha, K. E., Sanders, S. J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3529 · Cited by 367
A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., et al. (2014) · Nature Genetics · doi:10.1038/ng.2899 · Cited by 354
Self-citationKosmicki, J. A., Samocha, K. E., Howrigan, D. P., Sanders, S. J., Slowikowski, K., Lek, M., Karczewski, K. J., Cutler, D. J., Devlin, B., Roeder, K., et al. (2017) · Nature Genetics · doi:10.1038/ng.3789 · Cited by 340
Recurrent de novo mutations implicate novel genes underlying simplex autism risk
O'Roak, B. J., Stessman, H. A., Boyle, E. A., Witherspoon, K. T., Martin, B., Lee, C., Vives, L., Baker, C., Hiatt, J. B., Nickerson, D. A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6595 · Cited by 336
Self-citationHiatt, J. B., Pritchard, C. C., Salipante, S. J., O’Roak, B. J., & Shendure, J. (2013) · Genome Research · doi:10.1101/gr.147686.112 · Cited by 335
Progress toward treatments for synaptic defects in autism
Delorme, R., Ey, E., Toro, R., Leboyer, M., Gillberg, C., & Bourgeron, T. (2013) · Nature Medicine · doi:10.1038/nm.3193 · Cited by 218
Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID
van Bon, B. W. M., Coe, B. P., Bernier, R., Green, C., Gerdts, J., Witherspoon, K., Kleefstra, T., Willemsen, M. H., Kumar, R., Bosco, P., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.5 · Cited by 204
Self-citationPrevalence of autism in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis
Sun, X., Allison, C., Matthews, F. E., Sharp, S. J., Auyeung, B., Baron-Cohen, S., & Brayne, C. (2013) · Molecular Autism · doi:10.1186/2040-2392-4-7 · Cited by 200
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains
Geisheker, M. R., Heymann, G., Wang, T., Coe, B. P., Turner, T. N., Stessman, H. A. F., Hoekzema, K., Kvarnung, M., Shaw, M. A., Friend, K. L., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4589 · Cited by 187
Self-citationOligogenic heterozygosity in individuals with high-functioning autism spectrum disorders
Schaaf, C. P., Sabo, A., Sakai, Y., Crosby, J., Muzny, D., Hawes, A., Lewis, L., Akbar, H., Varghese, R., Boerwinkle, E., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr243 · Cited by 175
Autism traits in the RASopathies
Adviento, B., Corbin, I. L., Widjaja, F., Desachy, G., Enrique, N., Rosser, T., Risi, S., Marco, E. J., Hendren, R. L., Bearden, C. E., et al. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2013-101951 · Cited by 174
Disruption of POGZ Is Associated with Intellectual Disability and Autism Spectrum Disorders
Stessman, H. A. F., Willemsen, M. H., Fencková, M., Penn, O., Hoischen, A., Xiong, B., Wang, T., Hoekzema, K., Vives, L., Vogel, I., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.02.004 · Cited by 160
Self-citationOrosco, L. A., Ross, A. P., Cates, S. L., Scott, S. E., Wu, D., Sohn, J., Pleasure, D., Pleasure, S. J., Adamopoulos, I. E., & Zarbalis, K. S. (2014) · Nature Communications · doi:10.1038/ncomms5692 · Cited by 90
Tarailo‐Graovac, M., Zhu, J., Matthews, A., van Karnebeek, C., & Wasserman, W. W. (2017) · Genetics in Medicine · doi:10.1038/gim.2017.50 · Cited by 77
Akshoomoff, N. A., Mattson, S. N., & Grossfeld, P. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.86 · Cited by 73
Recurrent mutations in the CDKL5 gene: Genotype–phenotype relationships
Bahi‐Buisson, N., Villeneuve, N., Caietta, E., Jacquette, A., Maurey, H., Matthijs, G., Esch, H. V., Delahaye‐Duriez, A., Moncla, A., Milh, M., et al. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35401 · Cited by 61
Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders
Mitra, I., Lavillaureix, A., Yeh, E., Traglia, M., Tsang, K. M., Bearden, C. E., Rauen, K. A., & Weiss, L. A. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006516 · Cited by 48
NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse
Schuster, S., Rivalan, M., Strauß, U., Stoenica, L., Trimbuch, T., Rademacher, N., Parthasarathy, S., Lajkó, D., Rosenmund, C., Shoichet, S. A., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.42 · Cited by 26
Research works printed but not linked: 1
- Constantino JN, Gruber CP. Social responsiveness scale (SRS). Los Angeles: Western Psychological Services; 2005.
Cited by
Sorted by citations
Stenson, P. D., Mort, M. E., Ball, E. V., Chapman, M., Evans, K., Azevedo, L., Hayden, M., Heywood, S., Millar, D. S., Phillips, A. D., et al. (2020) · Human Genetics · doi:10.1007/s00439-020-02199-3 · Cited by 823
Neurodevelopmental Disorders: From Genetics to Functional Pathways
Parenti, I., Rabaneda, L. G., Schoen, H., & Novarino, G. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.004 · Cited by 687
Zhou, X., Feliciano, P., Shu, C., Wang, T., Astrovskaya, I., Hall, J. B., Obiajulu, J. U., Wright, J. R., Murali, S. C., Xu, S. X., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01148-2 · Cited by 453
Self-citationFrom cohorts to molecules: adverse impacts of endocrine disrupting mixtures
Caporale, N., Leemans, M., Birgersson, L., Germain, P.-L., Cheroni, C., Borbély, G., Engdahl, E., Lindh, C., Bressan, R. B., Cavallo, F., et al. (2022) · Science · doi:10.1126/science.abe8244 · Cited by 368
Exome 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
Self-citation
Metadata
- Authors
- Guo, H., Wang, T., Wu, H., Long, M., Coe, B. P., Li, H., Xun, G., Ou, J., Chen, B., Duan, G., Bai, T., Zhao, N., Shen, Y., Li, Y., Wang, Y., Zhang, Y., Baker, C., Liu, Y., Pang, N., Huang, L., Han, L., Jia, X., Liu, C., Ni, H., Yang, X., Xia, L., Chen, J., Shen, L., Li, Y., Zhao, R., Zhao, W., Peng, J., Pan, Q., Long, Z., Su, W., Tan, J., Du, X., Ke, X., Yao, M., Hu, Z., Zou, X., Zhao, J., Bernier, R. A., Eichler, E. E., & Xia, K.
- Affiliations
- Central South University (CN)
- University of Washington (US)
- Liuzhou Maternal and Child Health Hospital (CN)
- Shandong Mental Health Center (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Third Affiliated Hospital of Zhengzhou University (CN)
- Nanjing Brain Hospital (CN)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Guo, Hui
- Eichler, Evan E.
- Xia, Kun
- ORCID
- Guo, Hui
- Wang, Tianyun
- Coe, Bradley P.
- Li, Honghui
- Xun, Guanglei
- Ou, Jianjun
- Chen, Biyuan
- Bai, Ting
- Shen, Yidong
- Li, Yun
- Wang, Yazhe
- Zhang, Yu
- Liu, Yanling
- Pang, Nan
- Huang, Lian
- Han, Lin
- Jia, Xiangbin
- Liu, Cenying
- Yang, Xinyi
- Xia, Lu
- Chen, Jingjing
- Shen, Lu
- Li, Ying
- Zhao, Rongjuan
- Zhao, Wenjing
- Peng, Jing
- Pan, Qian
- Su, Wei
- Tan, Jieqiong
- Du, Xiaogang
- Ke, Xiaoyan
- Hu, Zhengmao
- Zou, Xiaobing
- Zhao, Jingping
- Bernier, Raphael A.
- Eichler, Evan E.
- Xia, Kun
- Venue
- Molecular Autism
- Published
- 2018-12
- Volume
- 9
- Issue
- 1
- Pages
- 64-64
- ISSN
- 2040-2392 (ISSN-L)
- PMC
- PMC6293633
- OpenAlex
- W2904691870
- Cited by
- 154
- References
- 40
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 22 · 2023: 21 · 2022: 31 · 2021: 26 · 2020: 27 · 2019: 12
- FWCI
- 9.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Autism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81330027, 81525007, 31671114, 31400919, 81601197, 81460500)
- Simons Foundation (SFARI 303241)
- National Institutes of Health (R01MH101221, R01MH100047)
- Howard Hughes Medical Institute (N/A)
- 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, developmental delay, autism risk genes, de novo mutations, inherited mutations, multi-factor models, genotype-phenotype correlation, autism candidate genes
- MeSH terms
- Autism Spectrum Disorder, Adult, Child, Female, Humans, Male, Models, Genetic, Mutation, Pedigree, Multifactorial Inheritance, Quantitative Trait Loci
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
