In the largest genetic sequencing study of autism spectrum disorder (ASD) to date, researchers have identified 102 genes associated with risk for autism. The study also shows significant progress towards teasing apart the genes associated with ASD from those associated with intellectual disability and developmental delay, conditions which often overlap. The study results are published online January 23 in the journal Cell.
For this study, an international team of researchers from more than 50 sites collected and analyzed more than 35,000 participant samples, including nearly 12,000 with ASD, the largest autism sequencing cohort to date. Using an enhanced analytic framework to integrate both rare, inherited genetic mutations and those occurring spontaneously when the egg or sperm are formed (de novo mutations), researchers identified the 102 genes associated with ASD risk. Of those genes, 49 were also associated with other developmental delays. The larger samples size of this study enabled the research team to increase the number of genes associated with ASD from 65 in 2015 to 102 today.
"This is a landmark study, both for its size and for the large international collaborative effort it required. With these identified genes we can begin to understand what brain changes underlie ASD and begin to consider novel treatment approaches," said Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai, and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.
Obtaining such a large sample was made possible by the Autism Sequencing Consortium (ASC), an international group of scientists who share ASD samples and data. Co-founded by Dr. Buxbaum in 2010 and originally funded by the Beatrice and Samuel A. Seaver Foundation and the Seaver Autism Center for Research and Treatment at Mount Sinai, the ASC is now a multiple-Principal Investigator grant funded by the National Institute of Mental Health.
In addition to identifying subsets of the 102 ASD-associated genes that have disruptive de novo variants more often in people with developmental delays or those with ASD, the researchers showed that ASD genes impact brain development or function and that both types of disruptions can result in autism. They also found that both major classes of nerve cells--excitatory neurons, which trigger a positive and activating change in the downstream neuronal membrane upon firing, and inhibitory neurons, which trigger a negative change upon firing--can be affected in autism.
"Through our genetic analyses, we discovered that it's not just one major class of cells implicated in autism, but rather that many disruptions in brain development and in neuronal function can lead to autism. It's critically important that families of children with and without autism participate in genetic studies because genetic discoveries are the primary means to understanding the molecular, cellular, and systems-level underpinnings of autism," said Dr. Buxbaum. "We now have specific, powerful tools that help us understand those underpinnings, and new drugs will be developed based on our newfound understanding of the molecular bases of autism."
About the Seaver Autism Center for Research and Treatment
The Seaver Autism Center is one of the most recognized institutions of its kind in the world because of its ability to translate breakthroughs in the lab to clinical trials that bring cutting-edge treatment to individuals affected by autism spectrum disorder (ASD) and associated neurodevelopmental disorders. We offer compassionate care, including assessment and behavioral health services, to children and families, as well as educational and community outreach programs. Founded in 1993 and located at the Icahn School of Medicine at Mount Sinai, families come from around the world to seek our services and the expert counsel of our team of scientists, researchers and clinicians.
For more information, visit: http://www.seaverautismcenter.org, or find the Seaver Autism Center on Facebook, Twitter and Instagram.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology, Mount Sinai St. Luke's and Mount Sinai West are ranked 23rd nationally for Nephrology and 25th for Diabetes/Endocrinology, and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally.
For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.