A new study from an international team of researchers investigates the relationship between the genetics underlying autism spectrum disorder and the expression of autism-related traits.
Their findings suggest that autism genes, including both new and inherited mutations, influence a range of behavioral and developmental traits that many people express, even if they're not considered to have autism. People diagnosed with an autism spectrum disorder, then, simply represent the most severe presentation of those traits.
“Almost all genetic risk factors for autism can be found in unaffected individuals,” wrote the authors in their introduction. “For example, most people who carry a 16p11.2 deletion, the most common large mutational risk factor for autism, do not meet criteria for an autism spectrum disorder diagnosis.”
Autism is a developmental disorder that affects about one in every 100 children, according to the authors. A child diagnosed with the disorder will not achieve some of the milestones of typical development, or might lose abilities they once gained. Characteristics of autism include a difficulty with communication, repetitive or routine behaviors, and sometimes narrow interests. That said, symptoms often vary from person to person with the term “spectrum” referring to autism’s wide range of possible symptoms, levels of disability, and positive skills. For example, some people with autism may not make eye contact, others are incapable of understanding simple instructions, and some demonstrate exceptional math skills. As they age, some children with autism learn to function more or less normally, while others require substantial support to perform even basic activities.
Most genetic studies of autism compare individuals with and without the disorder, explained the scientists. The most recent research estimates inherited mutations account for at least 20 percent of cases, while de novo mutations (spontaneous mutations not inherited from the parents) explain less than 5 percent of the total autism diagnoses. Autism stems from the combined small effects of thousands of genetic mutations, distributed across the genome, the research found.
“From the first published descriptions of autism, clinical and epidemiologic reports have commonly noted subthreshold traits of autism in the family members of many diagnosed individuals,” wrote the researchers, from University of Bristol, Harvard, MIT, and Massachusetts General Hospital.
In addition, many people without autism have little interest or capacity for social interaction and communication. What, then, are the genetic differences between someone with autism and someone without the disorder who has one or two similar behavioral traits?
To understand, the research team accessed data from a general population cohort, a family cohort of autism cases and their unaffected siblings, and several large, international studies of autism genetics. From there, they modeled comparisons and performed an analysis to untangle the different types of genetic risk and underlying mechanisms at work in any given instance of autism.
They discovered that each of us stands along a continuum of risk, that is made up of both common and rare genetic variants, along with environmental factors and chance events. This study demonstrates the genetic picture is much more complicated than whether someone has the autism disorder or not, since a range of genes and a range of possible genetic expressions contribute to each symptom (or trait) of the disorder. Like a music studio soundboard, many dials (genes) must be turned up high for someone to express behaviors within the spectrum to the degree worthy of diagnosis.
Going forward, the researchers expect their approach might be used to explore possible links between genetics and the individual features of other disorders, including schizophrenia.
Source: Robinson EB, St. Pourcain B, Anttila V, et al. Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population. Nature Genetics. 2016.