Common gene variants account for most of the genetic risk for autism

If "Nearly 60 percent of the risk" is genetic, then more than 40% of the risk is not. Environmental factors such as exposure to pollution could be what tips a person into being autistic.

PUBLIC RELEASE DATE: 20-Jul-2014
Contact: Elizabeth Dowling
The Mount Sinai Hospital / Mount Sinai School of Medicine
Common gene variants account for most of the genetic risk for autism

Nearly 60 percent of the risk of developing autism is genetic and most of that risk is caused by inherited variant genes that are common in the population and present in individuals without the disorder, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published in the July 20 edition of Nature Genetics.

"We show very clearly that inherited common variants comprise the bulk of the risk that sets up susceptibility to autism," says Joseph D. Buxbaum, PhD, the study's lead investigator and Director of the Seaver Autism Center for Research and Treatment and Professor of Psychiatry, Neuroscience and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. "But while families can be genetically loaded for autism risk, it may take additional rare genetic factors to actually produce the disorder in a particular family member."

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Although autism is thought to be caused by an interplay of genetic and other factors, there has been no consensus on their relative contributions and the nature of its genetic architecture. Recently, evidence has been mounting that genomes of people with autism are prone to harboring de novo mutations - rare, spontaneous mutations that exert strong effects and can largely account for particular cases of the disorder.

Specifically, the current study found that about 52.4 percent of autism was traced to common and rare inherited variations, with spontaneous mutations contributing a modest 2.6 percent of the total risk.

"Many people have been focusing on de novo mutations, such as the ones that can occur in the sperm of an older father," explains Dr. Buxbaum. "While we find these mutations are also key contributors, it is important to know that there is underlying risk in the family genetic architecture itself."

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"Within a given family, a de novo mutation could be a critical determinant that leads to the manifestation of autism spectrum disorder in a particular family member," says Dr. Buxbaum. "If the family has a common variation that puts it at risk, an added de novo mutation could push an individual over the edge and result in that person developing the disorder." [And exposure to pollution could give the push over the edge for some people.]