Autism genetics has made demonstrable progress in the past few years with the recognition of the role of de novo, or spontaneous, copy number variants (CNVs), loss-of-function point mutations and common inherited DNA variants. Although landmark studies have proved the important role of genetics, the common and robust finding is twofold: Hundreds of genes contribute to autism pathogenesis, but owing to limitations of statistical power and sample size, only a tiny fraction of them can be conclusively identified.

A barrier to achieving much greater power is the prohibitive cost (in money and time) of patient recruitment, phenotypic assessment and blood drawing. Mark Daly and his team at the Broad Institute and Massachusetts General Hospital have sought new models that might permit the rapid and inexpensive acquisition of many thousands of phenotypically validated DNA samples.

The researchers have formed a collaboration to explore a unique opportunity developed by the iPSYCH program in Denmark, led by Preben Mortensen at Aarhus University, to potentially obtain the largest single collection of DNA from people with autism and matched controls to date. By combining a nationwide psychiatric registry with DNA extracted from dried blood spots collected at birth from all Danish citizens since 1981, this collaboration could ultimately be able to analyze more than 15,000 cases of autism.

In this initial study, DNA extracted from neonatal blood spots in Denmark will be tested on genome-wide association study arrays to evaluate the use of amplified blood-spot DNA to study common variants and CNVs and an initial genome-wide autism study of more than 1,000 samples. Daly is simultaneously testing the accuracy of the sequencing of exomes — the coding regions of genomes — from blood spots at the same time.