The first common genetic risk factor for autism spectrum disorder has been identified by a multi-center team of researchers that included Margaret Pericak-Vance, Ph.D., director of the Miami Institute for Human Genomics at the University of Miami Miller School of Medicine.
Dr. Pericak-Vance and her collaborator Jonathan Haines, Ph.D. at Vanderbilt University Medical Center, joined the results of their study with those of Hakon Hakonarson, Ph.D., from Children’s Hospital of Philadelphia. The findings from the breakthrough study published online April 28 by the journal Nature may implicate a gene involved in forming the connections between brain cells. .
“Until now, no common genetic variant has been identified with such overwhelming evidence to support its role in autism spectrum disorders,” said Pericak-Vance, “The identification of a common variant for autism is a monumental achievement. Researchers have been looking for clues about the genetic architecture of autism for decades. Many thought that this day would never come, but we persisted.” .
The study included investigators from more than a dozen sites and participation of more than 10,000 subjects, including individuals with autism spectrum disorder, their family members and other volunteers from across the United States. .
“Each research team conducted a genome-wide association study of individuals with autism and controls, and found a significant association between autism and a region on chromosome 5 that is near two genes known as CDH9 and CDH10,” said Dr. Haines, lead investigator of the research team from Vanderbilt and director of the Vanderbilt Center for Human Genetics Research, “Both genes encode cadherins which are cell surface proteins thought to be important for establishing connections between cells in the developing brain and are candidate genes that may contribute to autism.” .
“Although no single gene is responsible for autism, cadherin is one of several proteins that affect the stability and maturation of nerve synapses in the brain, therefore this is an intriguing candidate for this region,” said John P. Hussman, Ph.D., one of the co-investigators in the research. “This discovery is important not only in its own right, but also because it offers important clues about specific biological processes we should investigate.” .
Since individuals with autism are so diverse, some researchers believed a common risk variant would never be found, but the advent of genome wide technology changed everything. “We’ve known that technology would evolve to where identification of the hardest to find genetic risk variants would be possible,” said Pericak-Vance. .
Haines added, “We also knew that the technology would require large numbers of patient participants as well as the tools and expertise to analyze data. We stayed invested and stayed on the cutting edge; it has paid off.” .
The study published in Nature reflects the collaborative efforts of research teams from the University of Miami Miller School of Medicine, Vanderbilt, Children’s Hospital of Philadelphia, the University of Washington in Seattle, and the University of California, Los Angeles. The institutions combined resources and datasets to achieve the genome-wide significant results. .
An independent publication in the Annals of Human Genetics details all the findings from the complete genome-wide study conducted by the University of Miami and Vanderbilt Medical Center on their independent datasets. Summary results from the candidate region on chromosome 5 were included in the Nature publication as they further support the overall finding. Deqiong Ma, M.D., Ph.D. is co-first author of both publications; other key authors on both publications are Michael L. Cuccaro, Ph.D., John R. Gilbert, Ph.D., and Daria Salyakina, Ph.D. from the Miami Institute for Human Genomics at the University of Miami Miller School of Medicine. .
Autism is among a spectrum of disorders and is a neurodevelopmental disorder characterized by three primary areas of impairment: social interaction, communication, and restricted and repetitive patterns of interest or behavior. Recent prevalence studies suggest that autism spectrum disorders may affect as many as 1 in 150 children in the United States, making it one of the most common neurodevelopmental disorders. .
Funding for the autism research conducted at the Miami Institute for Human Genomics and the Center for Human Genetics Research at Vanderbilt University comes from the National Institutes of Health and specifically from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, from Autism Speaks, and from the Hussman Foundation. Dr. Pericak-Vance is the Dr. John T. Macdonald Professor of Human Genetics.
Miller School of Medicine – University of Miami