Almost all autism spectrum disorders (ASD) risk factors that we know about are found in the unaffected, general population. (That’s what makes them risk factors, rather than genetic determinants.) And in that general population, there is a very wide range of social awareness, engagement in relationships, and communication styles.

The relationships among ASD genetic risk factors, normal variability in social functioning, and neuropsychiatric disorders (like ASD) have not been carefully examined. So a bunch of geneticists, psychiatrists, epidemiologists, and bioinformaticists decided it was time to examine it.

Genetic links to ASD—not causes of autism, but links to it—have been identified through genome wide-association studies. In these studies, the genetic variants present in people with ASD are compared to those of controls to see which variants might be associated with risk. This is the method by which genetic links to other psychiatric disorders have been identified, and it has been effective; over a hundred ASD associated mutations have been found this way.

The most common variants account for about 20 percent of cases, and rare mutations cover another three to four percent. But many people carry these variants that don't have an ASD diagnosis, and it wasn't clear what, if anything they were associated with there. The new study, published in Nature, shows that these variants are also associated with “normal” variation in social behavior.

They looked at three data sets to examine the association between genetic ASD risk variants and social difficulties. For the genetic variants, they used two genome-wide association studies that compare ASD cases to controls, one from Denmark and one from the US. For social difficulties, they used a general population cohort of kids born in Bristol, UK in 1991-2. When these kids were eight, their parents had completed the Social and Communication Disorders checklist, which asks about many typical ASD traits like awareness of others’ feelings.

They found that about a quarter of the genetic influences on ASDs also influence social difficulties in the general population. So these genetic variants are found in people who might seem socially a little off—they have trouble picking up on subtle facial cues or whatever—but not off enough to get a diagnosis of autism. In effect, this study is really putting the “spectrum” back into “autism spectrum disorders.”

And it turns out that ASD shares more genetic correlation with pediatric social and communication difficulties than it does with other neuropsychiatric disorders like schizophrenia, bipolar disorder, and major depressive disorder.

And it's not just inherited differences that are involved. The authors write that “cases and controls with equivalent quantitative levels of functional impairment, a key component of all psychiatric diagnoses, are highly similar with regard to de novo [new, as opposed to inherited] variant burden, suggesting that the current categorical threshold is largely arbitrary with regard to the social and communication impairments.”

There has been some controversy as to the degree to which ASD have a heritable component, since so many parents of people with the disorder are not themselves diagnosed with it. This study suggests that some of their parents are likely partially there, just flying under the diagnostic radar.

Nature Genetics, 2016. DOI: 10.1038/ng.3529 (About DOIs).