| Literature DB >> 23352160 |
Elaine T Lim1, Soumya Raychaudhuri, Stephan J Sanders, Christine Stevens, Aniko Sabo, Daniel G MacArthur, Benjamin M Neale, Andrew Kirby, Douglas M Ruderfer, Menachem Fromer, Monkol Lek, Li Liu, Jason Flannick, Stephan Ripke, Uma Nagaswamy, Donna Muzny, Jeffrey G Reid, Alicia Hawes, Irene Newsham, Yuanqing Wu, Lora Lewis, Huyen Dinh, Shannon Gross, Li-San Wang, Chiao-Feng Lin, Otto Valladares, Stacey B Gabriel, Mark dePristo, David M Altshuler, Shaun M Purcell, Matthew W State, Eric Boerwinkle, Joseph D Buxbaum, Edwin H Cook, Richard A Gibbs, Gerard D Schellenberg, James S Sutcliffe, Bernie Devlin, Kathryn Roeder, Mark J Daly.
Abstract
To characterize the role of rare complete human knockouts in autism spectrum disorders (ASDs), we identify genes with homozygous or compound heterozygous loss-of-function (LoF) variants (defined as nonsense and essential splice sites) from exome sequencing of 933 cases and 869 controls. We identify a 2-fold increase in complete knockouts of autosomal genes with low rates of LoF variation (≤ 5% frequency) in cases and estimate a 3% contribution to ASD risk by these events, confirming this observation in an independent set of 563 probands and 4,605 controls. Outside the pseudoautosomal regions on the X chromosome, we similarly observe a significant 1.5-fold increase in rare hemizygous knockouts in males, contributing to another 2% of ASDs in males. Taken together, these results provide compelling evidence that rare autosomal and X chromosome complete gene knockouts are important inherited risk factors for ASD.Entities:
Mesh：
Year: 2013 PMID： 23352160 PMCID： PMC3613849 DOI： 10.1016/j.neuron.2012.12.029
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173