New genetic discoveries from Autism Genome Project

An international consortium of researchers working under the auspices of Autism Speaks, the world's largest autism science and advocacy organization, has announced new genetic discoveries from the second phase of its collaborative study: the Autism Genome Project. The results were published today in the journal Nature, one of the world's most respected peer-reviewed scientific publications.

“In essence, we have identified specific genes that give rise to autism”

The Autism Genome Project (AGP) (www.autismgenome.org) consists of 120 scientists from more than 60 institutions representing 11 countries. Included in the consortium were scientists from Lucile Packard Children's Hospital and Stanford University. Joachim Hallmayer, M.D., associate professor of Psychiatry, and a member of the Stanford Autism Center at Packard Children's Hospital, noted the importance of the findings.

"In essence, we have identified specific genes that give rise to autism," Hallmayer said. "Recognizing the genetic factors that cause this complex disorder is a critical first step to better understanding and treating its different manifestations."

Based on analysis of high-density genotyping data collected from 1,000 individuals with autism spectrum disorder (ASD) and 1,300 without ASD, the AGP reported that individuals with autism tend to carry more submicroscopic insertions and deletions called copy number variants (CNV) in their genome than controls. Some of these CNV appeared to be inherited, while others are considered de novo, or new, because they are found only in affected offspring and not in the parents. Taken together, more of the CNVs disrupt genes, previously reported to be implicated in intellectual disability without autism or in autism, than expected by chance.

The new AGP study also identified new autism susceptibility genes including SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. Some of these genes belong to synapse-related pathways, while others are involved in cellular proliferation, projection and motility, and intracellular signaling, functional targets that may lead to the development of new treatment approaches.

These findings further support an emerging consensus within the scientific community that autism is caused in part by many "rare variants" or genetic changes found in less than one percent of the population. While each of these variants may account for only a small fraction of the cases, collectively they are starting to account for a greater percentage of individuals in the autism community, as well as providing insights into possible common pathogenic mechanisms. The overlap between autism susceptibility genes and genes previously implicated in intellectual disabilities further supports the hypothesis that at least some genetic risk factors are shared by different psychiatric developmental disabilities. Finally, identification of these biological pathways points to new avenues of scientific investigation, as well as potential targets for the development of novel treatments.

"Piece by piece, we are discovering genetic mutations that can cause autism. These findings will provide answers for families about what contributed to their autism," said Andy Shih, Ph.D., Autism Speaks vice president for scientific affairs. "Furthermore, as we have learned from examples involving other genetic risk factors of autism (e.g., Fragile X, Rett, TSC), these genetic findings help us understand the underlying biology of autism, which can lead to the development of novel treatments."

The Autism Genome Project (AGP) is an international autism genetics research consortium co-funded by Autism Speaks, the Medical Research Council, Canadian Institutes of Health Research, Health Research Board (Ireland), Genome Canada, and the Hilibrand Foundation. Additional support for Phase 2 of the AGP was provided by the National Institutes of Health.