Autism genetics has made remarkable progress in the last few years with the discoveries about
the role of de novo CNVs, loss-of-function point mutations, and common inherited DNA variation.
Still, of the hundreds of genes that contribute to autism, only a handful of them have been
conclusively identified because of limitations in sample size and statistical power- considerable
challenges because of the prohibitive cost and time-consuming nature of patient recruitment,
phenotypic assessment, and blood drawing. A groundbreaking collaboration between the Broad
Institute and the iPSYCH program in Denmark provides the opportunity for a genome analysis of
the largest single collection of samples from autism patients and matched controls to date. By
combining a nationwide psychiatric registry (Danish Psychiatric Central Registry — documenting
all inpatient (since 1969) and outpatient (since 1995) visits to public psychiatric treatment
facilities) with DNA extracted from dried blood spots collected at birth on all Danish citizens since
1981 and stored in a single facility (Statens Serum Institut in Copenhagen), more than 15,000
cases of autism have been identified and are available for genomic analysis. We will utilize a
dramatic advance in exome sequencing technology to perform deep exome analysis on 20,000
individuals at a dramatically lower price, thereby delivering the scale of data that should allow the
identification of scores of autism genes.