Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Synaptic, transcriptional and chromatin genes disrupted in autism

De Rubeis, Silvia, He, Xin, Goldberg, Arthur P., Poultney, Christopher S., Samocha, Kaitlin, Ercument Cicek, A., Kou, Yan, Liu, Li, Fromer, Menachem, Walker, Susan, Singh, Tarjinder, Klei, Lambertus, Kosmicki, Jack, Fu, Shih-Chen, Aleksic, Branko, Biscaldi, Monica, Bolton, Patrick F., Brownfeld, Jessica M., Cai, Jinlu, Campbell, Nicholas G., Carracedo, Angel, Chahrour, Maria H., Chiocchetti, Andreas G., Coon, Hilary, Crawford, Emily L., Crooks, Lucy, Curran, Sarah R., Dawson, Geraldine, Duketis, Eftichia, Fernandez, Bridget A., Gallagher, Louise, Geller, Evan, Guter, Stephen J., Sean Hill, R., Ionita-Laza, Iuliana, Jimenez Gonzalez, Patricia, Kilpinen, Helena, Klauck, Sabine M., Kolevzon, Alexander, Lee, Irene, Lei, Jing, Lehtimäki, Terho, Lin, Chiao-Feng, Ma'ayan, Avi, Marshall, Christian R., McInnes, Alison L., Neale, Benjamin, Owen, Michael J., Ozaki, Norio, Parellada, Mara, Parr, Jeremy R., Purcell, Shaun, Puura, Kaija, Rajagopalan, Deepthi, Rehnström, Karola, Reichenberg, Abraham, Sabo, Aniko, Sachse, Michael, Sanders, Stephan J., Schafer, Chad, Schulte-Rüther, Martin, Skuse, David, Stevens, Christine, Szatmari, Peter, Tammimies, Kristiina, Valladares, Otto, Voran, Annette, Wang, Li-San, Weiss, Lauren A., Jeremy Willsey, A., Yu, Timothy W., Yuen, Ryan K. C., Cook, Edwin H., Freitag, Christine M., Gill, Michael, Hultman, Christina M., Lehner, Thomas, Palotie, Aarno, Schellenberg, Gerard D., Sklar, Pamela, State, Matthew W., Sutcliffe, James S., Walsh, Christopher A., Scherer, Stephen W., Zwick, Michael E., Barrett, Jeffrey C., Cutler, David J., Roeder, Kathryn, Devlin, Bernie, Daly, Mark J., Buxbaum, Joseph D. and O'Donovan, Michael C. 2014. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 515 , pp. 209-215. 10.1038/nature13772

Full text not available from this repository.

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Additional Information: The DDD Study, Homozygosity Mapping Collaborative for Autism, UK10K Consortium, The Autism Sequencing Consortium,
Publisher: Nature Publishing Group
ISSN: 0028-0836
Date of Acceptance: 18 August 2014
Last Modified: 08 Jun 2020 09:00
URI: http://orca.cf.ac.uk/id/eprint/74821

Citation Data

Cited 1028 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item