Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci

نویسندگان

  • Stephan J. Sanders
  • Xin He
  • A. Jeremy Willsey
  • A. Gulhan Ercan-Sencicek
  • Kaitlin E. Samocha
  • A. Ercument Cicek
  • Michael T. Murtha
  • Vanessa H. Bal
  • Somer L. Bishop
  • Shan Dong
  • Arthur P. Goldberg
  • Cai Jinlu
  • John F. Keaney
  • Lambertus Klei
  • Jeffrey D. Mandell
  • Daniel Moreno-De-Luca
  • Christopher S. Poultney
  • Elise B. Robinson
  • Louw Smith
  • Tor Solli-Nowlan
  • Mack Y. Su
  • Nicole A. Teran
  • Michael F. Walker
  • Donna M. Werling
  • Arthur L. Beaudet
  • Rita M. Cantor
  • Eric Fombonne
  • Daniel H. Geschwind
  • Dorothy E. Grice
  • Catherine Lord
  • Jennifer K. Lowe
  • Shrikant M. Mane
  • Donna M. Martin
  • Eric M. Morrow
  • Michael E. Talkowski
  • James S. Sutcliffe
  • Christopher A. Walsh
  • Timothy W. Yu
  • David H. Ledbetter
  • Christa Lese Martin
  • Edwin H. Cook
  • Joseph D. Buxbaum
  • Mark J. Daly
  • Bernie Devlin
  • Kathryn Roeder
  • Matthew W. State
چکیده

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).

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عنوان ژورنال:
  • Neuron

دوره 87  شماره 

صفحات  -

تاریخ انتشار 2015