A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2020 | Number 2, Volume 34

Study explores risk of ASD for children if parents have a sibling with ASD

Children who have an aunt or uncle with an autism spectrum disorder (ASD) have an elevated risk of ASD, according to a new study. The study also calls into question the concept of a “female protective effect”—that is, the idea that females have a lower rate of ASD than males because more risk factors are required for girls to develop ASD. 

Dan Bai and colleagues analyzed data on nearly 850,000 Swedish children and their family members. Of the children, slightly more than 13,000 were diagnosed with autism. The researchers found that children of mothers with one or more siblings with ASD were approximately 3 times more likely than children in the general population to have ASD. Children of fathers with one or more siblings with ASD were twice as likely as children in the general population to have ASD. The difference between children of mothers with a sibling with ASD and children of fathers with a sibling with ASD was not statistically significant. Additionally, there was no significant difference in ASD risk for children whos uncles had ASD, compared to children whose aunts had ASD. 

In addition, the researchers say, “Within the second generation, ASD relative risk estimates did not differ between make and female offspring, contrary to the expected elevation for males under a female protective effect.” 

The researchers say their findings do not support the concept of a female protective effect, because such an effect “would imply that unaffected female individuals with a family history of ASD may carry and silently transmit proportionally greater genetic liability than unaffected male family members, amplifying recurrence rates in their male offspring, in particular.” 

They add, “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.”


“Inherited risk for autism through maternal and paternal lineage,” Dan Bai, Natasha Marrus, Benjamin Hon Kei Yip, Abraham Reichenberg, John N. Constantino, and Sven Sandin, Biological Psychiatry, May 2020 (free online). Address: Sven Sandin, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 6, SE-17177 Stockholm, Sweden, [email protected]


“Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism,” news release, NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development, May 18, 2020.