Rare variants and spontaneous glitches with genes is not the big culprit for autism, claims a new report, but rather versions of genes common in the population.
A National Institutes of Health research report cites heritability as the biggest risk factor, with 52 percent of the risk for autism was traced to common and rare inherited variation. In comparison spontaneous mutations contributes 2.6 percent of the total risk.
"Genetic variation likely accounts for roughly 60 percent of the liability for autism, with common variants comprising the bulk of its genetic architecture," explained Joseph Buxbaum, Ph.D., of the Icahn School of Medicine at Mount Sinai, in New York City. "Although each exerts just a tiny effect individually, these common variations in the genetic code add up to substantial impact, taken together," he states in an announcement of the research.
The findings of the Population-Based Autism Genetics and Environment Study Consortium, was published in the journal Nature Genetics.
"Thanks to the boost in statistical power that comes with ample sample size, autism geneticists can now detect common as well as rare genetic variation associated with risk," said Thomas R. Insel, M.D., director of the NIH's National Institute of Mental Health. "Knowing the nature of the genetic risk will reveal clues to the molecular roots of the disorder. Common variation may be more important than we thought."
The search for what causes autism has been a research focal point for years, with past studies indicating it's the result of an interplay of genetics and other factors, ranging from environmental to risk factors with pregnant mothers and risky behaviors by fathers.
"Recently, evidence has been mounting that genomes of people with autism are prone to harboring rare mutations, often spontaneous, that exert strong effects and can largely account for particular cases of disease," notes the announcement.
The study reports limitations of sample size and composition made it difficult to estimate the relative influence of such common, rare inherited, and rare spontaneous variation.
The study involved 3,000 people suffering from autism and new statistical methods that allowed researchers to more reliably sort out the heritability of the disorder. The researchers compared their results with a parallel study in 1.6 million Swedish families.
"This is a different kind of analysis than employed in previous studies," explained Thomas Lehner, Ph.D., chief of NIMH's Genomics Research Branch. "Data from genome-wide association studies was used to identify a genetic model instead of focusing just on pinpointing genetic risk factors. The researchers were able to pick from all of the cases of illness within a population-based registry."
"Within a given family, the mutations could be a critical determinant that leads to the manifestation of ASD in a particular family member," said Buxbaum. "The family may have common variation that puts it at risk, but if there is also a de novo [spontaneous} mutation on top of that, it could push an individual over the edge. So for many families, the interplay between common and spontaneous genetic factors could be the underlying genetic architecture of the disorder."
