Autism spectrum disorder and big brains are genetically linked

A link between autism spectrum disorders (ASDs) and big heads and brains have been established already for quite some years. With both ASDs and brain size being highly heritable, it was quite surprising that large scale genetic correlation analyses did not show any signficant genetic correlations between ASDs and brain size. Earlier research had already connected a specific group of genes, the genes from the mammalian target of rapamycin (mTOR) pathway, to brain size. Researchers Martina Arenella, Han Brunner and Janita Bralten from the department of Human Genetics had a closer look into this group of genes to investigate if they were also linked to ASDs and if they could genetically link ASDs and brain size.

In their research they were able to show that rare genetic variants in mTOR-related genes were also more common in individuals with ASDs compared to chance levels. In addition, when they investigated the complete set of common mTOR-related genetic variants in large scale genetic studies they showed associations to both ASDs and brain volume. This fueled their interest to study the genetic correlation between ASD and brain size in a different way. Instead of testing all genetic variants throughout the genome, they restricted their analysis to genetic variants that belong to the mTOR genes. Using this approach they found a positive genetic correlation between ASDs and brain volume captured by mTOR-related genetic variants, indicating that the risk for ASD is genetically linked to having a larger brain volume.

These results indicate that dissecting the genetic relationship by function has the potential to delineate shared biological mechanisms between complex traits, such as brain volume and ASDs. Our findings inform the need for further research on the mTOR signalling pathway as a potential target for treatment in ASD.

Publication

Arenella M, Mota NR, Teunissen MWA, Brunner HG, Bralten J. Autism spectrum disorder and brain volume link through a set of mTOR-related genes. J Child Psychol Psychiatry. 2023 Mar 15. doi: 10.1111/jcpp.13783. Epub ahead of print. PMID: 36922714.