Small differences in as many as a thousand genes contribute to risk for autism or autism spectrum disorder (ASD). This new study examined data on several types of rare, genetic differences in more than 14,000 DNA samples from parents, affected children, and unrelated individuals.
Most of the genes that contribute to autism remain unknown, but the current study increases the number of definitive autism genes almost fourfold to 33, compared to the 9 genes most closely tied to risk in recent years by similar studies in several labs.
It also identified more than 70 additional, likely ASD genes.
Each of these genes is mutated in more than 5 percent of individuals with autism, signifying a large, relative contribution to risk for a complex genetic disease.
By casting a wider net, a research team from 37 institutions found that previously unsuspected sets of genes may be involved in ASD risk, including some that control how nerve networks form in the brain. Occurring in one out of 68 children in the U.S., ASD affects a person’s social interactions, including communication, as well as behaviors with varying levels of severity.
Genetic analyses for autism
“The steps we added to our analysis over past studies provide the most complete theoretical picture to date of how many genetic changes pile up to affect the brains of children with autism,” said Joseph D. Buxbaum, PhD, Professor of Psychiatry, Neuroscience and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and Director of the Seaver Autism Center. Dr. Buxbaum is senior author for the Nature study, together with Mark J. Daly, PhD, co-director of the Program in Medical and Population Genetics at the Broad Institute of MIT and Harvard. “Beyond autism, we think this work will yield insights into what makes us social beings,” Dr. Buxbaum said.
“While we have very strong findings in these genetic analyses, newfound genetic discoveries must next be moved into molecular, cell and animal studies to realize future benefits for families,” added Dr. Buxbaum. “A study like this creates an industry for years to come, with labs worldwide checking the brain changes linked to each new genetic finding, and searching for drugs to counter them.”
Genetic differences in the sperm and eggs increase autism risk
For the first time, the study authors were able to assess the effects of both inherited genetic differences and those that happen spontaneously in the sperm and eggs that go on to form human embryos.
While small, rare genetic differences in the top 107 genes were found to confer a relatively large jump in a person’s risk, many more changes in other genes add smaller amounts of risk.
Thousand genes differences contribute to autism risk
According to the authors, the interplay between gene variations, both common and rare, holds the key to understanding autism. Along these lines, the team, by looking at how many times variations occurred in each of the 107 genes, was able to predict that small differences in about 1,000 genes will eventually be found to increase autism risk.
Assembling by far the largest autism study to date, the international research team collected and analyzed data from 3,871 autism cases, 2,270 sets of mothers, fathers and their affected children, and additional control samples.
This was achieved through the Autism Sequencing Consortium (ASC), originally funded by the Beatrice and Samuel A. Seaver Foundation and the Seaver Autism Center within the Icahn School of Medicine at Mount Sinai. The ASC is a multiple Principal Investigator grant funded by the National Institute of Mental Health (NIMH), with additional support from the National Human Genome Research Institute (NHGRI). In addition to Drs. Buxbaum and Daly, the PIs are Drs. Bernie Devlin (University of Pittsburgh School of Medicine)/Kathryn Roeder (Carnegie Mellon University), and Matthew State (University of California, San Francisco). Dr. Buxbaum is the communicating PI.
Source: Mount Sinai School of Medicine, USA