A study (https://www.ncbi.nlm.nih.gov/pubmed/25038753) published in 2014 showed that most of the genetic risk for autism is associated with genes that are very common in the population and not rarely occurring genes.
This large-scale study also showed that heritability is a much larger risk factor than any of the other known risk factors. Over 50% of the risk of autism was traced to common and rare inherited variation. Spontaneous mutations in the specific individual accounted for 2.6% of the total risk.
Most research result indicate that ASD is caused by an interplay of genetic factors and non-genetic factors, but there is no consensus regarding their relative contributions.
Big Swedish sample
The 2014 study used date from a large Swedish sample from Sweden’s universal health registry. Approximately 3,000 people diagnosed with autism was included in the study, plus matched controls. The researchers also compared their results with a parallel study of 1.6 million Swedish families that took into account date from twins and cousins, and factors such as the parent’s psychiatric history and the age of the father when the child was born.
“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 (NIMH). “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.”
Having access to a very large sample makes the results of the study more reliable. Previous research that have tried to measure the heritability of autism have used smaller samples and yield widely different results; from less than 20% heritability to roughly 50% heritability.
“This is a different kind of analysis than employed in previous studies,” says 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.”
Most genetic risk for autism resides with common variation.
Nature Genetics, online ahead of print July 20, 2014. doi:10.1038/ng.3039.