Autism study downplays role of genetics


Environmental factors may be more important than genes in determining whether a child develops autism, according to a controversial new analysis of the disorder in twins.

That finding runs counter to decades of prior research, which has generally found that genetic inheritance is the biggest determinant of a child’s risk of autism. The authors of the new study, published online Monday by the journal Archives of General Psychiatry, came to their conclusion after studying 192 pairs of identical and fraternal twins in which at least one twin met clinical criteria for the neurodevelopment disorder.

But the authors’ conclusion that environmental influences — perhaps chemical exposures, infections, diet or stress levels — could be so influential was roundly criticized by other autism experts.


“I think they’re really on shaky ground to say that,” said Dr. Paul Law, director of the Interactive Autism Network at the Kennedy Krieger Institute in Baltimore.

“It’s a massive claim,” said Angelica Ronald, a behavior geneticist at Birkbeck University of London. “It flies in the face of the previous data. I don’t see why the results have come out the way they have.”

The study authors acknowledged that their calculations were subject to a wide margin of error and thus could be incorrect. Still, they said that the analysis highlights the need for more research into environmental factors that may contribute to autism.

“Genetics don’t explain it,” said coauthor Neil Risch, a genetic epidemiologist at UC San Francisco. “They’re part of the story, but only part of the story.”

Scientific thinking on the causes of autism has undergone enormous shifts over the decades. For many years it was blamed on detached, unemotional “refrigerator mothers.”

But starting in the 1970s, a series of studies looking at twins recast autism as a genetic disorder. They found that if one twin had autism, the odds that the other had it too — a figure known as the concordance rate — depended primarily on how much DNA they shared.


If the twins were identical, the odds were 80% or higher. But if the twins were fraternal — and shared only half their DNA, on average — the odds were 10% or lower.

Those studies led scientists to zero in on genetics as the main cause of the disorder, which has been one of the world’s fastest-growing diagnoses over the last two decades. Researchers and activists have collected DNA samples from thousands of families, resulting in the discovery of a few dozen genes that appear to be associated with the disorder.

Since the 1990s, the definition of autism has expanded to include milder cases. Using the new definition, two recent studies have found that when one member of a fraternal twin pair had some form of the disorder, the odds that the other twin had it too were 31%.

In the latest study, researchers used records from the California Department of Developmental Services to identify children labeled with autism. They conducted their own exams on as many of those children as they could, ultimately building a database of 192 twin pairs in which at least one twin has the disorder.

For boys with any form of autism — the biggest group in the sample — the researchers found concordance rates of 77% for identical twin pairs and 31% for fraternal twin pairs. Those figures were in line with other recent studies.

Then they plugged those figures into a computer model that used statistical methods to account for the contributing roles of genetics, environmental factors that were shared by both twins and other environmental influences that weren’t shared. They calculated that 38% of the risk for autism came from genes and 58% came from the environment that twins shared.


“It took me a bit by surprise that the heritability of autism was so much lower than previous studies calculated,” said study leader Dr. Joachim Hallmayer, an expert on autism genetics at Stanford University.

But other scientists were highly skeptical.

“Their data is so similar to everybody else’s, and yet they come up with another conclusion,” said Robert Plomin, a behavioral geneticist at King’s College London. “I don’t know how this happened.”

Scientists have all but given up on finding a smoking gun that can explain large numbers of autism cases. Instead, they are looking for multiple risk factors that each have small effects. But the smaller the risk, the more difficult it is to find.

A case in point is another study — also published online Monday by Archives of General Psychiatry — that reported a link between antidepressant use by pregnant women and autism in their children.

Researchers identified 298 children in the Kaiser Permanente health system in Northern California who had been diagnosed with various forms of autism. Then they looked up the prescription records of their mothers and found that 6.7% had taken selective serotonin reuptake inhibitors, or SSRIs, while pregnant.

Among a control group of mothers of 1,507 children without an autism diagnosis, 3.3% had been on the medications. That led the researchers to conclude that SSRIs taken during pregnancy — especially during the first trimester, an important time for brain development — could modestly increase the risk of autism.


Other scientists said it was possible that the depressed mothers may have had some underlying biological condition that caused their depression and made their children more likely to develop autism. And the authors of the study said the findings should be read cautiously.

“We can’t determine causation from one study,” said study leader Lisa Croen, an epidemiologist who heads Kaiser’s Autism Research Program in Oakland.

She said that the potential risk from SSRIs should be weighed against the risk to the mother of not taking the drugs.