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New study advances the understanding of genetic basis of autism

by admin
August 19, 2022
in HEALTH CARE



A new study of genes underlying neurodevelopmental differences has uncovered more than 70 that are very strongly associated with autism and more than 250 with strong links to the condition. The analysis is the largest of its kind to date and includes more than 150,000 participants, 20,000 of whom have been diagnosed with autism.

The results offer the most comprehensive look yet at diverse forms of genetic variation in autism and in more broadly defined neurodevelopmental conditions. The insights shed light on the molecular roots of brain development and neurodiversity, and provide new avenues for future research on the biology of autism.

The findings result from a collaboration involving scientists and datasets from the Autism Sequencing Consortium, the Simons Foundation Powering Autism Research initiative, the Lundbeck Foundation Initiative for Integrative Psychiatric Research, the Population-Based Autism Genetics and Environmental Study, and the Center for Common Disease Genomics at the Broad Institute of the Massachusetts Institute of Technology and Harvard. The work is the culmination of an investment several years ago by these consortia to conduct large-scale genetic analysis for neurodevelopmental conditions and share these datasets on autism.

The new work appears in Nature Genetics, alongside three related studies that use some of the same data to advance the understanding of the genetic basis of autism.

We know that many genes, when mutated, contribute to autism and in this unprecedented study, we were able to bring together multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions. This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”


Joseph D. Buxbaum, PhD, co-senior author, 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

In an analysis led by co-first author Minshi Peng, then a graduate student in the lab of co-senior author Kathryn Roeder, PhD, a professor of statistics and life sciences at Carnegie Mellon University, the scientists examined the expression, or activity levels, of the genes they uncovered in developing human neurons. They learned that genes linked predominantly to developmental delay tend to be active in early neuronal development, whereas autism-related genes tend to play a role in more mature neurons. Furthermore, in an analysis of more than 20,000 samples from individuals with schizophrenia, the researchers found that genes that are strongly associated with autism were also more likely to be associated with genes that increase risk for schizophrenia.

“These analyses indicate that there are shared genetic risk factors between autism and other neurological and psychiatric disorders,” Dr. Buxbaum said.

“Our discoveries were enabled not only by very large-scale, rich data collections in autism research and population genetic studies, but also by newly developed analysis methods, allowing us to explore the genetic roots of neurodevelopmental variability in new ways. In addition to the massive gene discovery efforts in the field, we are beginning to make inroads into understanding where, when, and how these genes exert their effects during neurodevelopment,” said co-senior author Michael Talkowski, PhD, institute member at the Broad and director of the Center for Genomic Medicine at Massachusetts General Hospital.

Based on the study findings, Dr. Buxbaum said a precision medicine approach to autism would benefit patients, as treatments that work for individuals carrying a mutation in one gene may not work in other individuals carrying a mutation in a different gene.

“A critical takeaway is that autism has many genetic mutations driving it and thus genetic testing is warranted, not just for the benefit of families and individuals at risk for autism spectrum disorder, but also to drive development of therapeutics,” said Dr. Buxbaum. “The more we can advance therapeutics, based on the targets identified in these genetic findings, the more people we have the potential to help, which could have a significant impact in addressing autism and developmental delay worldwide.”

Additional co-senior authors on the study include Mark Daly, PhD (Broad and Center for Genomic Medicine at Massachusetts General Hospital), Bernie Devlin, PhD (University of Pittsburgh School of Medicine), and Stephan Sanders,PhD (University of California, San Francisco). Additional co-first authors include Harrison Brand, PhD, an assistant professor in neurology at Massachusetts General Hospital and Harvard Medical School; Jack Fu, a postdoctoral fellow in the Talkowski lab; and Kyle Satterstrom, a computational biologist in the Daly lab.

Source:

Mount Sinai Health System



Original Source Link

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