One explanation for autism

The genes that predispose a child to an autism spectrum disorder (ASD) exist for a reason. “On a population level,” says Yale researcher Renato Polimanti, some of them can “enhance cognitive ability.”

Evolution works to sweep away maladaptive mutations from a population. But some of the gene variants (called alleles) that increase the risk of autism persist in the Homo sapiens population because, Polimanti says, they appear to be beneficial—in small numbers. “Having, say, some of these so-called risk alleles associated with ASD may be good for the overall population, which is why there’s positive selection for them.” In other words, evolution keeps them around.

Polimanti is an associate research scientist in the medical school’s psychiatry department and the Veteran’s Administration health-care center in West Haven. He worked with Joel Gelernter, the Foundations Fund Professor of Psychiatry, on data from genome-wide association studies of European and US populations with ASD and other disorders. They concluded that one of probably many explanations for why ASD remains with us is a kind of genetics numbers game. Inheriting just some variant genes enhances brain function, but too many—no one knows the tipping point—will produce ASD. (The study appeared in PLOS Genetics.)

“There are at least two major genetic pathways that can lead to ASD,” says Polimanti. “One is a single mutation with huge effects, but this is rare. Far more commonly, we see the accumulation of thousands of variants in the genome with small effects.”

According to a 2016 report by the Centers for Disease Control and Prevention, about 1.5 percent of children in this country have ASD, and that number—1 in 68—has more than doubled since 2000 (although the increase is likely related to better reporting). Says Polimanti, “When it comes to mechanisms related to evolutionary adaptations, there’s generally no free lunch.”