Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci
Author
Sanders, S. J.
He, X.
Willsey, A. J.
Ercan-Sencicek, A. G.
Samocha, K. E.
Cicek, A. E.
Murtha, M. T.
Bal, V. H.
Bishop, S. L.
Dong, S.
Goldberg, A. P.
Jinlu, C.
Keaney, J. F.
Keaney III, J. F.
Mandell, J. D.
Moreno-De-Luca, D.
Poultney, C. S.
Robinson, E. B.
Smith L.
Solli-Nowlan, T.
Su, M. Y.
Teran, N. A.
Walker, M. F.
Werling, D. M.
Beaudet, A. L.
Cantor, R. M.
Fombonne, E.
Geschwind, D. H.
Grice, D. E.
Lord, C.
Lowe, J. K.
Mane, S. M.
Martin, D.M.
Morrow, E. M.
Talkowski, M. E.
Sutcliffe, J. S.
Walsh, C. A.
Yu, T. W.
Ledbetter, D. H.
Martin, C. L.
Cook, E. H.
Buxbaum, J. D.
Daly, M. J.
Devlin, B.
Roeder, K.
State, M. W.
Date
2015Source Title
Neuron
Print ISSN
0896-6273
Publisher
Cell Press
Volume
87
Issue
6
Pages
1215 - 1233
Language
English
Type
ArticleItem Usage Stats
137
views
views
205
downloads
downloads
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). Through analysis of de novo mutations in autism spectrum disorder (ASD), Sanders et al. find that small deletions, but not large deletions/duplications, contain one critical gene. Combining CNV and sequencing data, they identify 6 loci and 65 genes associated with ASD.
Keywords
AutismChild
Chromatin
Controlled study
Copy number variation
Female
Gene deletion
Gene duplication
Gene identification
Gene locus
Gene mutation
Gene sequence
Gene structure
Gene targeting
Genetic association
Genetic risk
Genotype
Human
Intellectual impairment
Major clinical study
Male
Priority journal
Risk assessment
Risk factor
Single nucleotide polymorphism
Synapse