Sleep disturbances in autistic children may be related to rare variants in insomnia risk genes.

According to a recent study, autistic (ASD) children seem more likely to have rare variations in genes linked to circadian rhythms and insomnia than their non-autistic siblings.

It has been noted that 40-80% of children on the spectrum suffer from sleep problems which can exacerbate other challenges associated with ASD. In fact, in previous studies that highlighted a genetic link for sleep issues in autisic subjects, it was noted that mice who were missing BMAL1—a significant circadian clock gene—have symptoms similar to those that often develop in autistic children such as atypical social behaviors and motor difficulties. It has even been found that autistic people who sleep well are two times as likely as non-autisic people to carry mutations in genes that regulate their circadian clocks.

This new study took a unique approach compared to previous studies in that it focused on copy number variants (CNVs) which are deletions or duplications of considerable portions of DNA. The researchers hypothesized that variants of genes that disrupt the pathways involved in circadian rhythms and insomnia are connected to ASD. Their goal was to “understand the relationship between autism risk, sleep disturbances, circadian pathways, and insomnia-risk genes.”

In order to test this hypothesis, they studied 5,860 ASD probands (individuals who are affected by a genetic condition) and 2,092 non-ASD siblings from the Simons Simplex Collection (SSC) and MSSNG database, along with 7,509 individuals from two unselected populations (IMAGEN and Generation Scotland). For SSC probands, both sleep duration and insomnia symptoms were based on reports by their parents.

Through this study, the researchers found 335 and 616 rare CNVs contained circadian and insomnia risk genes respectively. Deletions and duplications with circadian genes were disproportionately larger in ASD probands compared to siblings and unselected controls.

Further analysis demonstrated that deletions containing circadian and insomnia risk genes were better predictors of ASD risk compared to deletions containing other genes.

While their findings provide evidence for the contribution of circadian pathway dysfunction and its connection to ASD, how these genes increase ASD risk remain unknown. Rackeb Tesfaye, a graduate student in Mayada Elsabbagh’s lab at McGill University in Montreal, Canada, notes that since circadian rhythms guide multiple physiological processes such as cognition and hormone secretion, “It might be that circadian disruption at the gene level might be phenotypically linked to something that isn’t sleep.”

While these findings are important in better understanding genetic factors and the multiple complexities of the autistic experience, hopefully researchers can improve their methods in future studies. While their reports were not overrepresented in this study, it has been noted by other researchers that the use of parent reports can still be problematic as they can be subjective and lack accuracy. For example, even though a parent may observe and record when their child went to bed and woke up at specific times, they cannot accurately capture how long it took their child to fall asleep and how fragmented their sleep is. It’s possible that future studies could include the use of devices such as actigraphy (motion detecting wristwatches), but this could also prove to be too much of a sensory issue for autistic subjects. Be that as it may, these findings are extremely important and researchers have high hopes for similar future studies.