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Genetic Differences in Males and Females Diagnosed with Autism

Photo of a young girl

Emily Singer

Date Published: May 8, 2020

Autism is much more common in biological males than in biological females — boys are three to four times more likely to get a diagnosis than girls. Some of the difference may be due to biases in how autism is diagnosed. The condition can appear differently in males and females, and doctors may be more familiar with the symptoms that are most common in males.

But this isn’t the whole story. Growing evidence suggests that part of the difference is biological. Genetics and other biological factors, such as hormones, might protect biological females from developing autism. Scientists want to understand how they might be protected, with the hope this might help inspire new treatments.

A number of studies have suggested that it takes a bigger genetic ‘hit’ to cause autism in girls than in boys — on average, girls who have autism tend to have more gene changes than boys do.

To better understand how genes contribute to autism in biological males and females, Tychele Turner, a scientist at Washington University in St. Louis, and collaborators studied genetic information from thousands of people who have autism and other developmental disorders. They looked for gene changes that are more common in this group. They focused on people who have gene changes that are new, or ‘de novo’, meaning that the changes are not inherited from their parents.

Researchers found 25 genes that are linked to autism and other developmental disorders. But the specific genes that stood out differed depending on whether the researchers grouped people by biological sex. Seven genes stood out when they focused on biological females, three when they focused on biological males, and 15 in both sexes. The study was the first to look at how genetic differences in neurodevelopmental disabilities vary by biological sex.

Genes are arranged in structures in our cells called chromosomes. One pair of our 23 pairs of chromosomes, called the X and Y chromosomes, differs between biological males and biological females. Biological females have two copies of the X chromosome and all its genes, one from their mother and one from their father. Biological males have one copy of the X chromosome and all its genes, from their mother, and one copy of the Y chromosome and its genes, from their father.

Biological females have two copies of the X chromosome and all its genes, one from their mother and one from their father. Image showing how biological males have one copy of the X chromosome and all its genes, from their mother, and one copy of the Y chromosome and its genes, from their father.

To better understand the differences in autism risk genes found in biological females versus biological males, Turner looked at where these genes are found on the chromosomes. They found that five of the seven female-specific genes are located on the X chromosome. One of these genes, called DDX3X, is one of the most common genes linked to intellectual disability in females.

Turner says that these results highlight the need to study sex chromosome genes in neurodevelopmental disorders. It also shows that studying biological males and biological females separately can help to find different sets of autism risk genes. She says that studying larger numbers of people may identify more genes. Her team is now studying genetic data collected through SPARK.

Turner says that more research is needed to understand other factors that affect sex differences in autism, such as hormones.

Resources

Watch the SPARK webinar by Tychele Turner on Sex Bias and the Genetics of Autism

Further reading from Spectrum, an autism research news site funded by the Simons Foundation:

References

  • Turner T.N. et al. Am. J. Hum. Genet. 105, 1274-1285 (2019) PubMed
  • Jacquemont S. et al. Am. J. Hum. Genet. 94, 415-425 (2014) PubMed
  • Levy D. et al. Neuron 70, 886-897 (2011) PubMed