Exploring the Genetics of Autism: Is Autism Hereditary?

Autism Spectrum Disorder (ASD) is a very common neurodevelopmental disorder defined by differences in social interaction and communication and patterns of repetitive behaviors and restricted interests. About 1 in 36 kids are identified as having ASD at this time, according to the Centers for Disease Control (CDC). Some parents who are exploring whether or not their child has ASD may wonder: Is Autism hereditary? Could my child having Autism mean that another family member does, and can I have an autistic child even if no one else in my family is autistic?

"Hereditary" means that you inherit something from someone. "Genetic" is not the same thing as hereditary, meaning that whether via genetic mutation or otherwise, it does involve genes. The majority of Autism cases are genetic, and the diagnosis is largely hereditary. In short, Autism does run in families. It's likely that if your child has ASD, someone else in the family does, too, but this is not true 100% of the time.

This article will provide an in-depth overview of how genetics play a role in the development of Autism and its heritability, some of the specific genetic markers linked to Autism, and how environmental factors play a role in the possibility of ASD.

Understanding the Genetics of Autism

There are cases of idiopathic Autism where the cause of ASD is unknown. Idiopathic means "spontaneous" in medical jargon. However, the vast majority of people with ASD have a familial history of ASD. In fact, family history is the strongest known risk factor for ASD at this time.

How genetics play a role in the development of Autism

ASD has a strong genetic component. If you are born with gene changes associated with ASD, you inherit an increased likelihood of developing ASD but do not necessarily inherit ASD itself. This is why, of two kids born to the same two parents, one may have ASD, and the other may not. Genes carry information that contributes to certain traits or outcomes, but chance and other factors are still involved. For example, environmental influences can cause changes in genes. Gene mutations occur when the DNA sequence of a cell changes for any reason. This could happen due to DNA-damaging environmental factors or spontaneous mutations.

Overview of genetic risk factors for Autism

Although genetic mutations are possible for other reasons, most people with ASD develop it due to genetic mutations that run in their family. In other words, some people with ASD develop it based on chance and family history. For others, de novo genetic mutations could play a role. De novo mutations describe changes to the DNA sequence of a gene that has not occurred before within the family. This could be the cause of ASD for autistic children without any other family members who have or likely have ASD.

Fragile X syndrome is one of the top or leading genetic causes of ASD, with about one in three of those with Fragile X syndrome also having ASD. Even those with Fragile X syndrome who don't have ASD can share some traits common in autistic people, like differences in eye contact. Fragile X syndrome is also one of the leading causes of intellectual disability, which some, but not all, autistic people have.

Is Autism Hereditary?

At this time, it is understood that about 80% of Autism cases are connected to inherited genetic mutations. So, yes–Autism is hereditary, but it's a little bit more complex than that. Many research studies have been conducted on the heritability of ASD and related disorders, like attention deficit hyperactivity disorder (ADHD).

Discussion of studies and research on the heritability of Autism

There are different types of research studies, and some research studies tell us more than others depending on their design. For example, distinct types of studies, like a twin study vs. another type of study, can give us different kinds of information regarding the genetics of autism. Which of your family members has ASD could help identify how likely it is that you or someone else is born with ASD. For example:

• Identical twins: Twin studies have found that if one identical twin is born with ASD, it is highly likely that the other will be.
• Siblings: If you have one sibling with ASD, it's more likely that you'll have ASD. The likelihood increases more if you have two or more siblings with ASD.
• Parents: It was once believed that mothers were more likely carriers, but updated research shows that this isn’t the case. For example, a popular study conducted by professors Michael Wigler and Ivan Iossifov looked at the role fathers play in the likelihood of ASD. Now, we know that if either parent has ASD, a child is more likely to have it, too. 

It is clear that genetics play a significant role in whether or not someone will have ASD, even if natural gene variations aren't the only thing to impact an individual's risk or likelihood of having ASD. There are common variants genetic testing can look for to reveal possible ASD risk, which is why some families choose to pursue genetic testing.

Genetic Markers for Autism

It is often recommended that people with ASD get genetic testing. That said, there is no singular "Autism gene." Rather than look for a single gene, genetic testing looks for multiple possible markers. Note that if you get genetic testing personally, the provider who orders the test can go over your specific genetic markers in-depth. This can clear up any confusion that may emerge when attempting to go over the results on your own. Additionally, it is important to keep in mind that the presence of any potential marker does not automatically guarantee a diagnosis of ASD and you should always consult with a genetic counselor if you pursue genetic testing. Additionally, it is important to keep in mind that the presence of any potential marker does not automatically guarantee a diagnosis of ASD and you should always consult with a genetic counselor if you pursue genetic testing. With this in mind, let's go over some common variants we know of that are linked to ASD at this time.

Specific genetic markers linked to Autism

Genes associated with ASD include brain development genes, such as KDM6B (a known risk gene for ASD) and others. Common variants associated with ASD include but aren't limited to the following:

• ARID1B
• ASH1L
• CHD2
• DYRK1A
• POGZ
• SHANK3
• SYNGAP1

In idiopathic Autism (spontaneous cases) specifically, we often see the following variants:

• AVPR1a
• DISC1
• DYX1C1
• ITGB3
• SLC6A4
• RELN
• RPL10
• SHANK3  

One of the largest family studies conducted on ASD and genetics to date was published in the Proceedings of the National Academy of Sciences in July 2023. That study looked at 1,004 families containing at least two kids with ASD. In performing whole genome sequencing on 4,551 individuals from those families, researchers found seven possible genes predicted to lead to a higher risk of ASD. These include:

• PLEKHA8
• PRR25
• FBXL13
• VPS54
• SLFN5
• SNCAIP
• TGM1

Chromosome abnormalities (deletions or duplications) are seen in a significant portion of those diagnosed with ASD (about 40%). Chromosomal microarray analysis (CMA) can look for chromosomal abnormalities linked to ASD.

Potential implications of genetic testing for Autism

There can be pros and cons to genetic testing. Genetic testing can identify genes associated with ASD and other conditions. Some families get genetic testing to find out the likelihood that a future child will be born with ASD. Others get genetic testing to learn more about themselves. One possible drawback of genetic testing is that it isn't always reliable; it can't tell you for sure whether or not a child will have ASD. Furthermore, genetic testing can be costly, and in some cases, it may cause stress for parents and family members. 

Environmental Factors and Autism

While it is the strongest, family history is just one possible predictor of ASD. What about other factors? Some environmental factors are correlated with an increased likelihood of ASD in research. 

How environmental factors can interact with genetics to influence Autism risk

Environmental factors that can impact genes do not mean that a parent did something "wrong." It is well-established that parents do not “cause” children to develop ASD. It is well-established that parents do not “cause” children to develop ASD. The way conditions like Autism develop and how environmental factors interact with genetic contribution are both highly complex. While to varying degrees, chance pretty much always plays a role in whether or not a child ends up having ASD.

Environmental factors sometimes associated with Autism development include:

• Low birth weight or extreme prematurity (preterm birth).
• Any birth difficulty leading to oxygen deprivation (trouble getting oxygen to the baby's brain for a period of time for any reason).
• Immune system problems or metabolic problems affecting the person carrying the child.
• Exposure to air pollution or certain pesticides.

These are called environmental risk factors. Another possible risk factor for Autism is having an older parent. 

The complex interplay between genetics and the environment in Autism development

Sometimes, genetics create the possibility that a child will have a condition, but environmental factors “pull the trigger,” so to speak. In other words, genetic and environmental factors can work together to create what ultimately ends up being ASD. A baby with a genetic predisposition to ASD who also encounters an environmental risk factor (e.g., preterm birth, having an older parent) could be more likely to be born with ASD.

Conclusion

Autism Spectrum Disorder (ASD) can impact daily life in various ways and to different degrees. Special interests (intense interests in a specific topic), sensory sensitivities and differences (including being hypo or hypersensitive to stimuli), repetitive actions, words, or phrases, rigidity and trouble with minor changes, and differences in social communication and interaction are some common symptoms of ASD. 

Familial history of ASD is the strongest known risk factor for ASD at this time. Right now, we know of many genes that can be linked to ASD, but the reason someone has common variants associated with ASD can differ. For example, genetic mutations can be passed down from family members, but they can also happen as a result of changes caused by environmental influences. So, environmental factors can also play a role in whether or not someone has ASD. 

Future research on the genetic origins of ASD and ASD symptoms may assist in our continued understanding of ASD and how to best treat it.