Harmful mutations in a set of top autism genes crop up in Chinese individuals about as often as they do in people of European ancestry1. The findings, published 8 November in Nature Communications, suggest that mutations in these genes lead to autism regardless of a person’s genetic background.
“It’s fair to extrapolate the importance of these genes worldwide,” says lead researcher Evan Eichler, professor of genome sciences at the University of Washington in Seattle.
China’s big population makes it a good place to find people who carry rare mutations, says Eichler.
The study is the first to look in a large group of Chinese people for rare, spontaneous mutations associated with autism. Until now, most autism studies in China have focused on the role of milder genetic variants that are common in the general population.
“This is an important piece of work for studying autism in China,” says Zilong Qiu, a researcher at the Institute of Neuroscience in Shanghai, China, who was not involved in the study.
Many clinicians in China hold inaccurate perceptions of autism. Some believe autism is just another term for a developmental disability, Eichler says. In parts of the country, “autism really is a foreign concept,” he says.
Eichler teamed up with Chinese researchers to teach clinicians at more than 20 hospitals to recognize autism using the “Diagnostic and Statistical Manual of Mental Disorders.” The researchers asked the clinicians to request DNA samples from anyone diagnosed with autism, as well as their parents. They have so far sequenced the DNA from 1,543 individuals with autism and 2,090 parents.
They focused on 189 genes that have been linked to autism in individuals of European descent. They found 271 severe mutations in these genes in Chinese people with autism, compared with 65 in the parents.
Of the mutations found in people with autism, 43 arose spontaneously. These so-called de novo mutations are in 29 of the 189 genes.
“I so was relieved when I saw the first de novo mutations coming out and they were same genes we had seen, more or less, in the European cohort,” Eichler says. “[I thought,] ‘Hallelujah, this is exactly what we had hoped it would be.’”
Roughly 4 percent of Chinese people with autism in the study have de novo mutations in these candidate genes for autism. Researchers have found a similar rate of mutations in these genes in people of European ancestry.
Still, this type of mutation accounts for only a fraction of autism cases in the population, says Lucia Peixoto, assistant professor of medicine at Washington State University, who was not involved in the new work.
China’s large population provides an important source of individuals with rare mutations in candidate genes for autism.
For example, the researchers found 12 people with autism who have de novo mutations in SCN2A — a leading candidate gene for autism. This doubles the number of known people with autism who carry mutations in the gene. The scientists also identified four people with mutations in CHD8 — another high-ranking autism gene.
The rate of mutations in SCN2A appears to be higher among Chinese individuals than among people of European descent, but this finding may be an artifact, Eichler says. SCN2A mutations are typically found in individuals with intellectual disability.
Stigma surrounds autism in China, and so the parents who seek a diagnosis may be more likely to be those of severely affected children. The researchers may also have prioritized sequencing the more severely affected individuals first, Eichler says.
The families of two people with CHD8 mutations and three with SCN2A mutations agreed to return to the clinic for a detailed medical workup. So far, their features match those seen in individuals of European ancestry who have the same mutation. For example, both individuals with CHD8 mutations have large heads and are overweight, as seen in other individuals characterized so far.
Expanding this type of analysis to all the genes in the genome is likely to reveal more about the genetics of autism in China, Qiu says. Qiu is sequencing every gene in a group of Chinese people with autism.
The researchers are continuing to collect DNA from people with autism across China. They have samples from 3,000 individuals with autism and their parents, and expect to enroll as many as 2,000 additional people with autism each year.