Risk estimated at 3 to 5 percent vs. 1.5 percent in general population
According to new research from the National Institutes of Health (NIH), a child who has a parent with a sibling on the spectrum is more likely to be diagnosed with autism spectrum disorder (ASD) compared to the general population. The study, published in Biological Psychiatry, analyzed health records of approximately 850,000 children born in Sweden between 2003-2012. Using the Swedish National Patient Register and the Multi-Generation Register, information on ASD diagnoses in both the child and parental generations was recorded.
Close to 13,000 Swedish children ended up with an autism diagnosis, about 1.5 percent of the cohort. However, children whose mothers had one or more siblings with autism were three times more likely to have ASD than the general population and children whose fathers had one or more siblings on the spectrum were twice as likely to be diagnosed with autism than the general population. The study considered the slightly higher autism risk rate of children from mothers who had a sibling with ASD to that of the fathers to be insignificant. The research also reported that the autism risk rate was not different if the parent had a brother versus a sister with autism.
Ultimately, the researchers found that 3 to 5 percent of children whose parents have a sibling on the spectrum also have autism themselves. This points to a 100 to 230% increased chance of developing the disorder compared to the 1.5 percent autism rate in the general population. According to the authors, this is the first epidemiological study to provide an autism risk estimate for children with aunts or uncles on the spectrum.
Since autism was first identified, a strong male to female (4:1) bias has been recognized. This rate disparity has had many researchers consider if a female protective effect exists, the idea that females have a built-in resistance to the disorder for unknown reasons. The female protective effect theory further speculates that women could carry autism risk factors but remain unaffected. However, these women could transfer the risk to their sons who lack the same protective effect and therefore may later develop autism.
John Constantino, a co-author of the study, sheds light on this issue and says, “This finding challenges the existence of the a female protective effect, because if such an effect existed, the children of mothers with a sibling with ASD could be expected to have up to a 30% higher risk of ASD. Similarly, the researchers found no statistically significant increase in ASD risk for children whose uncles have ASD, compared to children whose aunts have the condition.”
In the long run, the authors felt their study’s importance lies in future generations, since recognizing a higher familial risk for autism could point to earlier screenings and treatments for infants and toddlers. The study’s conclusion states, “We found similar ASD risk in offspring from maternal and paternal lineages. The risk of ASD in offspring of siblings of ASD probands equals but does not exceed what has been observed for second-degree relatives within a single generation. These findings do not suggest female protective factors as the principal mechanism underlying the male sex bias in ASD. While these results mitigate concern for amplification of maternally transmitted ASD risk, they affirm the importance of heightened surveillance for ASD in second-generation offspring. Given the benefits of early intervention, these results support incorporating second-degree family history of ASD in pediatric practice, as well as future studies involving behavioral phenotyping and genotyping to advance individualized estimates of ASD recurrence risk.”
References
Dan Bai, Natasha Marrus, Benjamin Hon Kei Yip, Abraham Reichenberg, John Constantino, Sven Sandin. Inherited Risk for Autism Through Maternal and Paternal Lineage. Biological Psychiatry. April 2, 2020.
Jake Gockley, A Jeremy Willsey, Shan Dong, Joseph D Dougherty, John N Constantino, Stephen Sanders. The Female Protective Effect in Autism Spectrum Disorder is Not Mediated by a Single Genetic Locus. Molecular Autism. May 13, 2015.
NIH News Release. Autism Risk Estimated at 3 to 5% for Children Whose Parents Have a Sibling with Autism. May 18, 2020.
