A multi-institution team led by USC faculty has received a five-year, $8.4 million grant from the National Institutes of Health for an ambitious effort to survey the genetic, physical and behavioral profiles of children with autism.
The grant vastly will increase the reach and ethnic diversity of the Autism Genetic Resource Exchange (AGRE), the world’s largest database for autism research, overseen by Clara Lajonchere, research assistant professor at the USC Viterbi School of Engineering with a joint appointment at the Keck School of Medicine of USC.
Lajonchere, who serves as vice president of clinical programs for Autism Speaks, said: “This reaffirms the NIH’s commitment to supporting the AGRE resource, the largest repository of clinical and genetic information for families with two or more kids with autism. AGRE represents a paradigm shift towards large-scale collaboration and data sharing in the research community.”
The NIH grant will double the number of families in AGRE and expand the data beyond genetic and clinical profiles to include what the researchers call phenomics: the systematic study of the outward physical and behavioral marks of autism.
The research will be organized under a new Center for Genomic and Phenomic Studies in Autism. One goal of the new center, said Thomas Lehner, chief of the NIH Genomics Research Branch, is to better distinguish among the many forms of autism and to explore the differences in their genetic profiles.
“We are trying to establish a correspondence between gene and phenotype, with the phenotype being autism and its many manifestations,” Lehner said. “A unique feature of this grant is the extensiveness of phenotyping. This is one of our largest projects, if not the largest.”
Autism is an umbrella term that includes several phenotypes, Lehner said, some of which are poorly understood. A better picture of the phenotypes of autism could provide a basis for future drug trials and give clinicians better methods for measuring a patient’s response to treatment, he added.
AGRE’s expansion will focus on recruiting an ethnically diverse group of families, since Caucasians have been over-represented in genetic studies to the point that diagnostic tools are unreliable for minorities, Lajonchere said.
“There are few focused genetic studies that directly examine minority populations,” she said. The center’s expansion will complement efforts by Lajonchere and colleagues at Autism Speaks to foster similar studies in other countries.
Another unique aspect of the grant is a program of pilot studies to evaluate potential environmental factors in autism such as air pollution or disease and diet during pregnancy.
In one such study, Constantinos Sioutas, professor of civil and environmental engineering at the USC Viterbi School of Engineering, will chart exposure to air pollution in more than 600 California children with autism.
“Part of this study is aimed at determining whether chemical species in airborne ultrafine particles are associated with the incidence of autism in children,” Sioutas said.
Lajonchere credited Steven Moldin, executive director of USC’s Washington, D.C. Office of Research Advancement and co-director of the new center, for helping “to create a presence for autism and autism research at USC.”
Earlier this year, Moldin organized a three-day meeting at USC of the country’s leading autism researchers to discuss the shared neurobiological roots of autism and other developmental disorders.
“Autism is such a complicated disorder, that you need to bring dozens of different research paradigms to understand it. In that way, it’s the ultimate multidisciplinary disease,” said Moldin, who is also research professor of psychiatry and behavioral sciences at the Keck School.
“If I had to think of one disease that could unite researchers from the most fields at USC, it would definitely be autism.”
Randolph Hall, vice provost for research advancement, said, “This grant further demonstrates how USC is expanding its portfolio of research that directly addresses critical societal issues.”
“We’re hoping to really fast-track some findings and the understanding of the causes and environmental factors that could possibly be implicated in autism,” Lajonchere said.
Since its founding by Cure Autism Now in 1997, AGRE has grown under Lajonchere’s leadership to include data from more than 1,500 families with multiple cases of autism. AGRE became part of Autism Speaks when that organization merged with Cure Autism Now in February.
Along with Lajonchere and Moldin, David Amaral of the MIND Institute at the University of California, Davis will serve as co-director of the new center. Besides USC, AGRE and UC Davis, the other institutions involved in the center are Childrens Hospital Los Angeles, the University of Michigan at Ann Arbor and the University of Massachusetts Medical School.