Synaptic, transcriptional and chromatin genes disrupted in autism View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-11

AUTHORS

Silvia De Rubeis, Xin He, Arthur P. Goldberg, Christopher S. Poultney, Kaitlin Samocha, A Ercument Cicek, Yan Kou, Li Liu, Menachem Fromer, Susan Walker, Tarjinder Singh, Lambertus Klei, Jack Kosmicki, Shih-Chen Fu, Branko Aleksic, Monica Biscaldi, Patrick F. Bolton, Jessica M. Brownfeld, Jinlu Cai, Nicholas J. Campbell, Angel Carracedo, Maria H. Chahrour, Andreas G. Chiocchetti, Hilary Coon, Emily L. Crawford, Lucy Crooks, Sarah R. Curran, Geraldine Dawson, Eftichia Duketis, Bridget A. Fernandez, Louise Gallagher, Evan Geller, Stephen J. Guter, R. Sean Hill, Iuliana Ionita-Laza, Patricia Jimenez Gonzalez, Helena Kilpinen, Sabine M. Klauck, Alexander Kolevzon, Irene Lee, Jing Lei, Terho Lehtimäki, Chiao-Feng Lin, Avi Ma'ayan, Christian R. Marshall, Alison L. McInnes, Benjamin Neale, Michael J. Owen, Norio Ozaki, Mara Parellada, Jeremy R. Parr, Shaun Purcell, Kaija Puura, Deepthi Rajagopalan, Karola Rehnström, Abraham Reichenberg, Aniko Sabo, Michael Sachse, Stephan J. Sanders, Chad Schafer, Martin Schulte-Rüther, David Skuse, Christine Stevens, Peter Szatmari, Kristiina Tammimies, Otto Valladares, Annette Voran, Li-San Wang, Lauren A. Weiss, A. Jeremy Willsey, Timothy W. Yu, Ryan K.C. Yuen, , , , , Edwin H. Cook, Christine M. Freitag, Michael Gill, Christina M. Hultman, Thomas Lehner, Aarno Palotie, Gerard D. Schellenberg, Pamela Sklar, Matthew W. State, James S. Sutcliffe, Christopher A. Walsh, Stephen W. Scherer, Michael E. Zwick, Jeffrey C. Barrett, David J. Cutler, Kathryn Roeder, Bernie Devlin, Mark J. Daly, Joseph D. Buxbaum

ABSTRACT

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones. More... »

PAGES

209

References to SciGraph publications

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  • Journal

    TITLE

    Nature

    ISSUE

    7526

    VOLUME

    515

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature13772

    DOI

    http://dx.doi.org/10.1038/nature13772

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1041044240

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25363760


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