Common variations of genes account for at least 49% of the distribution of autism, according to a new study in Nature Genetics. Another 10% is explained by other known genetic causes, while 41% is unaccounted for – including both environmental factors and genetic influences yet to be identified.
The research is based on a sample of 3000 Swedish children with autism compared with a matched control group. The Swedish universal health registry offers access to genetic data unavailable in most countries.
"Genetic variation likely accounts for roughly 60% of the liability for autism, with common variants comprising the bulk of its genetic architecture," explained Dr Joseph Buxbaum, of the Icahn School of Medicine at Mount Sinai (ISMMS). "Although each exerts just a tiny effect individually, these common variations in the genetic code add up to substantial impact, taken together."
Rare genetic variations which make a large contribution to the possibility of having a condition are easier to pick up than more common ones that raise the chances slightly. The paper notes, “Individual risk-associated genes have been identified from rare variation, especially de novo mutations. From this evidence, one might conclude that rare variation dominates the allelic spectrum in autism, yet recent studies show that common variation, individually of small effect, has substantial impact en masse.”
In fact the paper finds that de novo mutations – ones that did not occur in either parent, account for just 2.6% of autism risk, while 3% is from rare inherited genetic factors. “For many families, the interplay between common and spontaneous genetic factors could be the underlying genetic architecture of the disorder," says Buxbaum.
The study is not the first to attempt to assess the heritability of autism, with past estimates ranging from 17% to 50%. As such it is unlikely to be the last word. However, Dr Thomas Lehner of the National Institute of Mental Health, who was not an author of the paper says, "This is a different kind of analysis than employed in previous studies. Data from genome-wide association studies was used to identify a genetic model instead of focusing just on pinpointing genetic risk factors.” Genome-wide association studies are increasingly being used to tease out complex conditions where susceptibility is raised by a wide variety of alleles, none of which come close to guaranteeing the condition will be inherited.
Despite the rare risk factors, such as spontaneous mutations and deletions in genetic material accounting for only a small part of the autism propensity, they make for easier research targets to understand how autism occurs, just as mutations in the BRCA1 and 2 genes have provided enormous benefits in studying breast cancer, while being responsible for only a small proportion of cases.