Autism and genetics

Sanders SJ, He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE, Cicek AE, Murtha
MT, Bal VH, Bishop SL, Dong S, Goldberg AP, Jinlu C, Keaney JF 3rd, Klei L,
Mandell JD, Moreno-De-Luca D, Poultney CS, Robinson EB, Smith L, Solli-Nowlan T,
Su MY, Teran NA, Walker MF, Werling DM, Beaudet AL, Cantor RM, Fombonne E,
Geschwind DH, Grice DE, Lord C, Lowe JK, Mane SM, Martin DM, Morrow EM, Talkowski
ME, Sutcliffe JS, Walsh CA, Yu TW; Autism Sequencing Consortium, Ledbetter DH,
Martin CL, Cook EH, Buxbaum JD, Daly MJ, Devlin B, Roeder K, State MW. Insights
into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.
Neuron. 2015 Sep 23;87(6):1215-33.

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).

Highlights

• De novo copy number variants (dnCNV) are associated with Autism Spectrum Disorder/ASD
• De novo mutations are associated with ASD in individuals with a high IQ
• Small de novo deletions, but not large dnCNVs, contain one high-effect ASD risk gene
• Identifies 6 ASD loci and 65 ASD genes, many of which target chromatin or the synapse

 https://www.doximity.com/doc_news/v2/entries/2072624