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

Neuron
Authors
Keywords
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).

Year of Publication
2015
Journal
Neuron
Volume
87
Issue
6
Pages
1215-33
Date Published
2015 Sep 23
ISSN
1097-4199
DOI
10.1016/j.neuron.2015.09.016
PubMed ID
26402605
PubMed Central ID
PMC4624267
Links
Grant list
MH19961-14 / MH / NIMH NIH HHS / United States
R01 MH074090 / MH / NIMH NIH HHS / United States
MH100233 / MH / NIMH NIH HHS / United States
R37 MH057881 / MH / NIMH NIH HHS / United States
R01 MH097849 / MH / NIMH NIH HHS / United States
MH100209 / MH / NIMH NIH HHS / United States
U01 MH100229 / MH / NIMH NIH HHS / United States
MH074090 / MH / NIMH NIH HHS / United States
R01 DC009410 / DC / NIDCD NIH HHS / United States
T32 MH019961 / MH / NIMH NIH HHS / United States
U01 MH100209 / MH / NIMH NIH HHS / United States
U01 MH100239 / MH / NIMH NIH HHS / United States
DC009410 / DC / NIDCD NIH HHS / United States
MH100239 / MH / NIMH NIH HHS / United States
MH100229 / MH / NIMH NIH HHS / United States
R01 MH057881 / MH / NIMH NIH HHS / United States
P30 DC005188 / DC / NIDCD NIH HHS / United States
Canadian Institutes of Health Research / Canada
MH071584-07 / MH / NIMH NIH HHS / United States
R25 MH071584 / MH / NIMH NIH HHS / United States
T32 MH014276 / MH / NIMH NIH HHS / United States
Howard Hughes Medical Institute / United States
MH057881 / MH / NIMH NIH HHS / United States
U01 MH100233 / MH / NIMH NIH HHS / United States