PUBLIC RELEASE DATE:

20-Jul-2014

Contact: Elizabeth Dowling newsmedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Nearly 60 percent of the risk of developing autism is genetic and most of that risk is caused by inherited variant genes that are common in the population and present in individuals without the disorder, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai and published in the July 20 edition of Nature Genetics.

"We show very clearly that inherited common variants comprise the bulk of the risk that sets up susceptibility to autism," says Joseph D. Buxbaum, PhD, the study's lead investigator and Director of the Seaver Autism Center for Research and Treatment and Professor of Psychiatry, Neuroscience and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. "But while families can be genetically loaded for autism risk, it may take additional rare genetic factors to actually produce the disorder in a particular family member."

Dr. Buxbaum and colleagues of the Population-Based Autism Genetics and Environment Study (PAGES) Consortium conducted a rigorous analysis of DNA sequence variations from an ongoing, comprehensive study of autism in Sweden.

Although autism is thought to be caused by an interplay of genetic and other factors, there has been no consensus on their relative contributions and the nature of its genetic architecture. Recently, evidence has been mounting that genomes of people with autism are prone to harboring de novo mutations - rare, spontaneous mutations that exert strong effects and can largely account for particular cases of the disorder.

Specifically, the current study found that about 52.4 percent of autism was traced to common and rare inherited variations, with spontaneous mutations contributing a modest 2.6 percent of the total risk.

"Many people have been focusing on de novo mutations, such as the ones that can occur in the sperm of an older father," explains Dr. Buxbaum. "While we find these mutations are also key contributors, it is important to know that there is underlying risk in the family genetic architecture itself."

Gauging the collective impact on autism risk of variations in the genetic code shared by most people, individually much subtler in effect, has proven to be even more challenging. Limitations in sample size and composition have made it difficult to detect these effects and to estimate the relative influence of such common, rare inherited and rare, spontaneous de novo variation. Differences in methods and statistical models have also resulted in estimates of autism heritability ranging from 17 to 50 percent.

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Common gene variants account for most of the genetic risk for autism

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