A Neurodevelopmental Disorder

Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex origins. In 2009, our group published two papers in the journal Nature, which have had a broad impact on the field of autism research.

Although twin studies suggest that ASDs are highly heritable, specific genes have been difficult to identify. We conducted a genome-wide association study (GWAS) on a group of 780 families (3,101 individuals) with affected children, a second group of 1,204 affected individuals, and 6,491 controls, all of whom had European ancestry. GWAS allows us to examine an individual’s entire genome. By comparing genomics variations between the groups, we identified six genetic markers between two specific genes that confirmed susceptibility to ASDs. This was the first study to demonstrate a genome-wide significant association of this kind. The two genes, cadherin 10 and cadherin 9 are sticky molecules that help neurons bind together. They play an important role in neurodevelopment, and may be important in helping us understand the neuropathology of autism.

In 2009, we published a second paper in the journal Nature that identified copy number variations (CNVs) as important genetic features in autism. CNVs are relatively large changes in DNA that are marked by regions that are absent (deletions) or the opposite, regions that have extra copies of a particular gene (duplications). In this whole-genome CNV study, we examined 859 autism cases and 1,409 healthy children of European ancestry. The autism group had significantly more CNVs on or near genes that had previously been associated with the disorder. Further, we identified several new susceptibility genes in ubiquitin networks that were associated with the autism group. Ubiquitins are small proteins that help to destroy unneeded or damaged proteins. Damage to ubiquitin networks can theoretically cause neurological changes that may underlie autism and are an important avenue for future research into the disorder.

Kai Wang was first author on the GWAS paper, which was published in Nature.

Joseph Glessner was first author on the CNV paper, which was published in Nature.