Genetic changes are responsible for roughly 60 percent of the risk for autism, and most of these variants are commonly found in the general population, according to a groundbreaking study led by Joseph D. Buxbaum, PhD, 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.

The remaining nongenetic factors that account for roughly 40 percent of the risk for autism are not known. However, environmental factors and the interaction between genes and the environment may be a part of these nongenetic factors, says Dr. Buxbaum, the G. Harold and Leila Y. Mathers Research Professor of Geriatrics and Adult Development at Icahn School of Medicine.

Findings from the four-year study—called the Population-Based Autism Genetics and Environment Study (PAGES) Consortium—were published in the July 20, 2014, issue of Nature Genetics.

In the study, the largest of its kind ever undertaken, Mount Sinai researchers worked in collaboration with Swedish scientists, analyzing 500,000 common genetic variants from 3,046 people, of whom 466 had autism. The team then corroborated their results with a longitudinal Swedish study that followed more than 1.6 million families, and included more than 14,000 individuals with autism.

“Most of the risk for autism is found in common variants, but we know that in a specific individual, a spontaneous mutation or other rare mutation is often the decider, with the interaction between the common variants and rare mutations leading to the diagnosis,” Dr. Buxbaum says. “There was already evidence two years ago that both common and rare genetic variation contributed to autism. Using this unique sample, we were able to make it perfectly clear regarding relative contributions, and showed that common variation is significantly more important than generally appreciated.” The study was funded by the National Institutes of Health (NIH) and the Beatrice & Samuel A. Seaver Foundation.

Dr. Buxbaum is currently leading a multinational consortium that is completing a study of 3,800 individuals with autism to identify spontaneous and other rare mutations, as well. The consortium is using advanced methods to look at every gene in the genome.

“Together, with support from the NIH and enormous philanthropy from the Seaver Foundation, and others, we are able to be very aggressive in advancing the field, and defining the next generation of diagnostic tools and treatments for autism, both behavioral and pharmacological,” says Dr. Buxbaum.