| Literature DB >> 26402605 |
Stephan J Sanders1, Xin He2, A Jeremy Willsey3, A Gulhan Ercan-Sencicek4, Kaitlin E Samocha5, A Ercument Cicek6, Michael T Murtha4, Vanessa H Bal3, Somer L Bishop3, Shan Dong7, Arthur P Goldberg8, Cai Jinlu8, John F Keaney9, Lambertus Klei10, Jeffrey D Mandell3, Daniel Moreno-De-Luca11, Christopher S Poultney8, Elise B Robinson12, Louw Smith3, Tor Solli-Nowlan13, Mack Y Su14, Nicole A Teran15, Michael F Walker3, Donna M Werling3, Arthur L Beaudet16, Rita M Cantor17, Eric Fombonne18, Daniel H Geschwind19, Dorothy E Grice20, Catherine Lord21, Jennifer K Lowe19, Shrikant M Mane22, Donna M Martin23, Eric M Morrow24, Michael E Talkowski25, James S Sutcliffe26, Christopher A Walsh27, Timothy W Yu27, David H Ledbetter28, Christa Lese Martin28, Edwin H Cook29, Joseph D Buxbaum8, Mark J Daly12, Bernie Devlin10, Kathryn Roeder30, Matthew W State31.
Abstract
Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1).Entities:
Mesh：
Year: 2015 PMID： 26402605 PMCID： PMC4624267 DOI： 10.1016/j.neuron.2015.09.016
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173