Autism study downplays role of genetics

Written by Sandeep Nehra

The analysis, which goes against decades of research, says that environmental factors may be more important than genes in determining whether a child develops autism. The conclusion is criticized by other experts in autism.

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

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

But the authors conclude that environmental influences – perhaps the exposure to chemicals, infections, diet or levels of stress – can be as influential was criticized by other experts in autism.

“I think it is 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 geneticist at the behavior at Birkbeck University of London. “It goes against previous data. I do not see why the results have come from the way they have.”

The study authors acknowledged that their estimates were subject to wide margins of error and therefore may be incorrect. Still, said the analysis highlights the need for more research on the environmental factors that may contribute to autism.

“Genetics does not explain,” said co-author Neil Risch, genetic epidemiologist at the University of San Francisco. “They are part of history, but only a part of history.”

Scientific thinking about the causes of autism has undergone enormous changes over the decades. For many years, blaming the individual, without emotions “refrigerator mothers.”

But from the 1970s, a series of studies examining autistic twins recast as a genetic disorder. They found that if one twin had autism, the likelihood that the other had it too – a figure known as the concordance rate – depends primarily on the amount of DNA they shared.

If the twins are identical, the odds were 80% or more. But if the fraternal twins – and they share only half their DNA on average – the odds are 10% or less.

These studies led scientists to zero in genetics as the main cause of the disease, which has been one of the fastest growing diagnoses in the world during the past 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 a member of a pair of fraternal twins have some form of the disease, the likelihood that the other twin also had was 31%.

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

For children with some form of autism – the largest group of the sample – the researchers found concordance rates of 77% of pairs of identical twins and 31% of the pairs of fraternal twins. These figures were in line with other recent studies.

Then connected to the data in a computer model that uses statistical methods to take into account the roles that contribute to genetics, environmental factors that were shared by the twins and other environmental influences that were not shared. It is estimated that 38% of the risk of autism came from the genes and 58% came from the environment that twins share.

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

But other scientists were skeptical.

“Their data are very similar to everyone else, and still reach any other conclusion,” said Robert Plomin, a geneticist at the behavior at the University of London King. “I do not know how this happened.”

Scientists have given up on finding a smoking gun that can explain a large number of cases of autism. Instead, they are looking for multiple risk factors that each has a small effect. However, the lower the risk, the harder it is to find.

An example of this is another study – also published online Monday in the journal Archives of General Psychiatry – that reported a link between use of antidepressants in pregnant women and autism in children.

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

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

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

“We can not determine the causality of a study,” said study leader Lisa Croen, an epidemiologist who heads the Autism Research at Kaiser in Oakland.

He said the potential risk of SSRIs should be weighed against the risk to the mother of not taking medications.