The female protective effect in autism

It hasn’t escaped the notice of autism researchers that boys are far more likely to have autism spectrum disorders (ASD) than are girls. In fact, the ratio is something like four afflicted males for every female. This could be because boys are at particular risk for some reason or that girls have some sort of protection from ASD. After comparing almost 10,000 pairs of dizygotic (non-identical) twins, Elise Robinson of Harvard Medical School and her colleagues concluded that when it comes to ASD, there is a ‘female protective effect’.

As the name ‘autism spectrum’ implies, there is huge range of behaviors and symptoms associated with the disease. Individuals can have varying degrees of each trait and different combinations of traits. This no doubt reflects the fact that whole suites of genes that have been implicated with ASD, with similarly afflicted individuals having completely different genotypes and environmental histories. Nevertheless, family members of people who test high for autistic behaviors are more likely to display such behaviors themselves. Here’s where the twins come in.

The researchers argued that if there were a female protective effect, then it would require more drastic genetic changes in girls than in boys to result in the same degree of autistic behavior. In other words, a girl with autism would have a greater number of genetic changes, on average, than a boy with autism. That being the case, there’s a greater chance that a girl’s siblings, who share half her DNA, would also be impaired than a boy’s siblings. This would be particularly true of twins who shared the same womb environment.

To be clear, we already know that ASD is largely inheritable and that the siblings of children with ASD are more likely to have the disorder themselves. The question is whether there’s a difference between the siblings of boys and the siblings of girls with ASD. Short answer: yes there is. The fraternal twins of girls who scored at the top 10% for ASD traits were 38% more likely to also score that high than were the twins of boys.

If there is a female protective effect, we don’t yet know what it is. However it functions, it only further complicates the morass that is ASD genetic studies since researchers now have to take gender into account when looking for genetic causes. Still, anything that furthers our understanding of this disorder is a good thing.

Elise B. Robinson, Paul Lichtenstein, Henrik Anckarsäter, Francesca Happé, & Angelica Ronald (2013). Examining and interpreting the female protective effect against autistic behavior Proceedings of the National Academy of Sciences of the United States of America : DOI:10.1073/pnas.1211070110.