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How does autism vary between the sexes?
There are around four times more males diagnosed with autism than females, but the reasons are not fully understood. The current thinking is that females do not develop some of the symptoms possibly because of genetic, hormonal, environmental or epigenetic mechanisms.

Could the difference be down to genes?
In very simplistic terms, a mutated gene linked to autism may be present in boys and girls, but in girls it might not cause the same autistic behaviours. There could be a factor, including genes, that somehow overrides the mutation.

Do environmental influences play a part?
If you think that autism is a combination of genes and environmental factors, then there may be something in females that staves off the effect of environmental factors such as parental age or exposure to chemicals. For example, prenatal hormones like oestrogen could have an influence during development.

Could there be other such mechanisms?
I want to stress that we don鈥檛 think of this effect as genetic, environmental or developmental factors working in isolation. It is most likely to be a combination. An influence in females may be the way brains in girls develop compared with boys. And boys may project some symptoms of autism more profoundly, whereas girls might cover them up through verbal abilities that develop differently to those of boys.

How will you find these factors?
We have launched the Autism Sisters Project, which will initially look at genetic and epigenetic factors. Large data sets for studying influential effects are lacking, so we want to reach out to families that have a child with autism and an unaffected sister who have not participated in a study before. We will also add information from earlier studies that include a non-diagnosed sibling. By pooling all this, we hope to get answers.

Are there other examples of conditions that affect females differently?
Club foot is a prime one. Girls have this less often but have more genetic mutations that would cause it, so it is interesting that they don鈥檛 have as many cases. That鈥檚 called the Carter effect.

Is the ultimate hope that this will help treat symptoms of autism?
That鈥檚 the hope. Whatever leads to less autism in females may be something that is effective in intervention. If there is a molecule that can help ameliorate some symptoms, then that really is the long-term goal. But whether or not we find a factor, we will be opening the door to a better understanding of autism just by studying it.

Who can join the study?
We are seeking participants in New Jersey, New York and Connecticut, but we hope to add other sites in the US and include studies from outside the country.

This article appeared in print under the headline 鈥淐alling the sisters of autism鈥�