Cited by 341Genomics and Rare DiseasesGenetics and Neurodevelopmental DisordersAutism Spectrum Disorder Research

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Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples

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Kosmicki, Jack A, Samocha, Kaitlin E, Howrigan, Daniel P, Sanders, Stephan J, Slowikowski, Kamil, Lek, Monkol, Karczewski, Konrad J, Cutler, David J, Devlin, Bernie, Roeder, Kathryn, Buxbaum, Joseph D, Neale, Benjamin M, MacArthur, Daniel G, Wall, Dennis P, Robinson, Elise B, Daly, Mark J·2017·Nature Genetics

DOI 10.1038/ng.3789PMC PMC5496244

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Abstract

Recent research has uncovered an important role for de novo variation in neurodevelopmental disorders. Using aggregated data from 9,246 families with autism spectrum disorder, intellectual disability, or developmental delay, we found that ∼1/3 of de novo variants are independently present as standing variation in the Exome Aggregation Consortium's cohort of 60,706 adults, and these de novo variants do not contribute to neurodevelopmental risk. We further used a loss-of-function (LoF)-intolerance metric, pLI, to identify a subset of LoF-intolerant genes containing the observed signal of associated de novo protein-truncating variants (PTVs) in neurodevelopmental disorders. LoF-intolerant genes also carry a modest excess of inherited PTVs, although the strongest de novo-affected genes contribute little to this excess, thus suggesting that the excess of inherited risk resides in lower-penetrant genes. These findings illustrate the importance of population-based reference cohorts for the interpretation of candidate pathogenic variants, even for analyses of complex diseases and de novo variation.

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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587
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Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014
Baio, J., Wiggins, L., Christensen, D. L., Maenner, M. J., Daniels, J., Warren, Z., Kurzius-Spencer, M., Zahorodny, W., Robinson, C., Rosenberg, et al. (2018) · MMWR. Surveillance Summaries · doi:10.15585/mmwr.ss6706a1 · Cited by 6,078
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
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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
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Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) · Nature Genetics · doi:10.1038/ng.2711 · Cited by 2,263
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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
Rate of de novo mutations and the importance of father’s age to disease risk
Kong, A., Frigge, M. L., Masson, G., Besenbacher, S., Sulem, P., Magnusson, G., Gudjonsson, S. A., Sigurdsson, A., Jonasdottir, A., Jonasdottir, A., et al. (2012) · Nature · doi:10.1038/nature11396 · Cited by 2,134
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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
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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
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Chen, C., Guo, S., Shi, Y., Gu, X., Xu, Z., Chen, Y., Gu, Y., Qin, N., Jiang, Y., Dai, J., et al. (2025) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2025.07.008 · Cited by 2
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Pang, N., Li, K., Tan, S., Chen, M., He, F. P., Chen, C., Yang, L., Zhang, C., Deng, X., Yang, L. C., et al. (2023) · Gene · doi:10.1016/j.gene.2023.148071 · Cited by 2
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He, M., Liu, L., Luo, S., Wang, J., Guo, J., Wang, P., Zhai, Q., He, S., Zou, D., Liu, X., et al. (2023) · medRxiv · doi:10.1101/2023.07.16.23292551 · Cited by 2
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Wang, X., Ling, Z., Luo, T., Zhou, Q., Zhao, G., Li, B., Xia, K., & Li, J. (2022) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-022-05824-4 · Cited by 1
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Davis, K., Serrano, M. A., Martin, M. M., Vanzo, R. J., Rimmasch, M., Hom, Y., Uddin, M. J., & Bilancia, C. G. (2021) · Scientific Reports · doi:10.1016/s1096-7192(21)00488-1 · Cited by 1
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Shohat, S., & Shifman, S. (2019) · doi:10.1101/567073 · Cited by 1
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Authors: Kosmicki, 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., Buxbaum, J. D., Neale, B. M., MacArthur, D. G., Wall, D. P., Robinson, E. B., & Daly, M. J.
Affiliations: Broad Institute (US)
University of California, San Francisco (US)
Emory University (US)
University of Pittsburgh (US)
Carnegie Mellon University (US)
Icahn School of Medicine at Mount Sinai (US)
Stanford Medicine (US)
Corresponding author: Daly, Mark J
ORCID: Kosmicki, Jack A
Samocha, Kaitlin E
Howrigan, Daniel P
Sanders, Stephan J
Slowikowski, Kamil
Lek, Monkol
Karczewski, Konrad J
Cutler, David J
Devlin, Bernie
Roeder, Kathryn
Buxbaum, Joseph D
Neale, Benjamin M
MacArthur, Daniel G
Wall, Dennis P
Robinson, Elise B
Daly, Mark J
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2017-02-13
Volume: 49
Issue: 4
Pages: 504-510
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng.3789
PMC: PMC5496244
OpenAlex: W2949181286
Cited by: 340
References: 48
Citations by year: 2026: 12 · 2025: 20 · 2024: 35 · 2023: 22 · 2022: 34 · 2021: 38 · 2020: 46 · 2019: 54 · 2018: 45 · 2017: 34
FWCI: 32.49
Type: journal article
Language: en
Open access: green
doi.org
Licence: cc-by-nd
www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
eScholarship (California Digital Library) (submittedVersion)
Funders: Simons Foundation (SFARI 342292)
National Alliance for Research on Schizophrenia and Depression
Simons Foundation Autism Research Initiative
National Institutes of Health (5k01mh099286-02, T32 HG002295/HG/NHGRI)
Simons Center for the Social Brain, Massachusetts Institute of Technology
National Institute of Mental Health (U01MH100209, U01MH111661, U01MH100229, R01MH097849, U01MH111658, U01MH100239, R56MH097849, K01 MH099286, U01MH111660, U01MH100233)
National Human Genome Research Institute (T32 HG002295/HG/NHGRI, HG002295, T32HG002295)
National Institute of General Medical Sciences (R01GM104371)
National Institute of Diabetes and Digestive and Kidney Diseases (U54DK105566)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords: neurodevelopmental disorders, autism spectrum disorder, intellectual disability, developmental delay, loss-of-function intolerance, ExAC, inherited mutations, genetic risk
MeSH terms: Autism Spectrum Disorder, Humans, Intellectual Disability, Phenotype, Genetic Variation, Genetic Predisposition to Disease, Exome, Neurodevelopmental Disorders

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Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples

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