Skip navigation

Calls to Action

Research Group Quadruples Number of Known High-Risk Autism Genes

October 29, 2014

Report increases number of genes strongly tied to autism to more than thirty, providing many new targets for experimental treatments

A new international study has identified 22 genes that convey a high risk of autism. This quadruples the number of known high-risk autism genes – to more than 30 – and considerably expands the list of potential targets for new treatments.

The research, supported in part by Autism Speaks, also suggests that as many as a thousand genes – most of them still unknown – contribute some measure of risk for the disorder. The report appears today in Nature.

“This international study gives us a new genetics ‘parts-list’ to inform future research, diagnostics and medicine development,” says co-author Stephen Scherer. Dr. Scherer heads the McLaughlin Centre at the University of Toronto and the Centre for Applied Genomics at Toronto’s Hospital for Sick Children.

Dr. Scherer also directs Autism Speaks’ whole genome sequencing program. Formerly called AUT10K, this program is now known as MSSNG, for the missing answers it promises to deliver.

Unlike whole genome sequencing, today’s Nature report involved more-conventional genetic testing that looked only at protein-coding genes. The genes control development and body functions. However, they make up just two percent of a person’s DNA. The remaining 98 percent was once considered “junk,” but is now recognized as helping ensure that the right genes turn on at the right time and place in the brain and body.

“With this level of gene-based analysis complete, the stage is set for applying whole genome sequencing to complete the description of the genetic anatomy involved in autism and delivering even greater benefits to the autism community,” Dr. Scherer says.

“[These] newfound genetic discoveries must next be moved into molecular, cell and animal studies to realize future benefits for families,” adds study co-author Joseph Buxbaum. An Autism Speaks-funded researcher, Dr. Buxbaum directs the Seaver Autism Center, at the Icahn School of Medicine at Mount Sinai, in New York City. The next step, Dr. Buxbaum says, will involve “labs worldwide checking the brain changes linked to each new genetic finding and searching for drugs to counter them.”

The study’s authors belong to the Autism Sequencing Consortium. Founded in 2010, the international group includes autism researchers from 37 institutions who share anonymous genetic and biological data from their study participants. Compiling these resources, the group scanned for genetic differences in more than 14,000 DNA samples – making this the largest genetic analysis of autism to date.

Genes converge on three pathways
In the study, the gene changes that produced the greatest autism risk tended to affect one of three pathways required for healthy brain development, the researchers say.

* One pathway involves enzymes that influence when specific genes turn on or off during brain development.

* Another pathway involves genes that govern synapses, the gaps between nerve cells that control whether a nerve signal travels forward.

* A third pathway involves genes that regulate how other genes are translated into proteins.

Boys versus girls
The new study was among the first to compare the autism risk that different classes of mutations produce in girls versus boys. Boys are more than four times as likely to develop autism, suggesting that something partially protects girls from the disorder. In other words, girls appear to need a more powerful genetic “hit” before they develop autism. For this reason, comparing the effect of suspected autism risk genes between girls and boys enabled the authors to estimate the degree of risk associated with each gene change. Using this approach, they identified mutations that increased autism risk more than 20-fold.

Greater understanding of these high-risk genes – in particular their normal function – may provide guidance for future treatments. 

Autism Speaks Senior Director of Neuroscience Dan Smith provided further comment on the findings to CNN Health and the Pittsburgh Tribune. Follow the links to read more.