Research Explained: Phenotypic effects of genetic variants associated with autism

Research Explained: Phenotypic effects of genetic variants associated with autism

Authors: Thomas Rolland, Freddy Cliquet, Richard J. L. Anney, Clara Moreau, Nicolas Traut, Alexandre Mathieu, Guillaume Huguet, Jinjie Duan, Varun Warrier, Swan Portalier, Louise Dry, Claire S. Leblond, Elise Douard, Frédérique Amsellem, Simon Malesys, Anna Maruani, Roberto Toro, Anders D. Børglum, Jakob Grove, Simon Baron-Cohen, Alan Packer, Wendy K. Chung, Sébastien Jacquemont, Richard Delorme & Thomas Bourgeron

Written by: Gabrielle Rushing, PhD, Chief Scientific Officer, CSNK2A1 Foundation

Link to paper: Rolland, T., Cliquet, F., Anney, R.J.L. et al. Phenotypic effects of genetic variants associated with autism. Nat Med 29, 1671–1680 (2023). https://doi.org/10.1038/s41591-023-02408-2

[LINK TO: https://www.nature.com/articles/s41591-023-02408-2]

Research Explained Summary

This study looked at how certain genetic changes linked to autism might affect thinking skills, education, and life outcomes. The researchers found that people who carry these genetic variants tend to have slightly lower problem-solving abilities, are less likely to complete higher levels of education, and may earn less money on average. They were also more likely to receive disability benefits, suggesting these genetic factors can have a broader impact beyond autism itself.

This study doesn’t mean that everyone with these genetic changes will experience these challenges, but it highlights how genes can shape different aspects of life. Understanding these connections can help researchers and doctors better support individuals with autism and related traits, while also challenging stereotypes—many people with autism have unique strengths that aren't captured by traditional measures of intelligence or success.

What did the study find related to OCNDS?

OCNDS is caused by variants in the CSNK2A1 gene. The study included the CSNK2A1 gene as one of the autism-associated genes analyzed for rare loss-of-function (LoF) variants. Here are the key findings related to CSNK2A1:

• CSNK2A1 was identified among genes carrying rare variants that are more frequent in individuals with autism compared to undiagnosed individuals.

• The study estimated an autism odds ratio (OR) for CSNK2A1, which quantifies how strongly the variants in this gene are associated with autism.

• What is an odds ratio? An odds ratio is a way of comparing how likely something is to happen in one group versus another. If the odds ratio is greater than 1, it means the event is more likely in the first group; if it's less than 1, the event is less likely in that group.

• CSNK2A1 had an odds ratio (OR) of ~20.

• An odds ratio (OR) of ~20 means that individuals who have a LoF mutation in the CSNK2A1 gene are 20 times more likely to be diagnosed with autism compared to individuals who do not have a mutation in this gene.

• The study showed that genes linked to synaptic function and transcription regulation, including CSNK2A1, tend to have higher autism ORs.