What Genes Do Autism and ADHD Share?

What you need to know

• About one-third of genetic variants linked to autism are also associated with ADHD
• About one-fifth of genetic variants linked to ADHD are also associated with autism
• Some genes appear to be uniquely associated with either autism or ADHD
• Having more traits of one condition may increase risk for the other condition

Autism and ADHD: Closely Related Conditions

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two common neurodevelopmental conditions that often occur together. About one-third of children with autism also meet criteria for ADHD, and about 15% of children with ADHD meet criteria for autism. While the core symptoms differ - autism involves social communication difficulties and restricted interests/behaviors, while ADHD involves inattention, hyperactivity and impulsivity - there is considerable overlap in how these conditions manifest.

Researchers have long wondered about the reasons for this overlap and frequent co-occurrence. Are there shared genetic factors that increase risk for both conditions? Do some genes uniquely contribute to autism or ADHD? And does having one condition directly increase risk for the other?

A new study led by Dr. Hugo Peyre and colleagues aimed to tackle these questions using powerful genetic analysis techniques. By examining data from large genome-wide association studies of autism and ADHD, the researchers were able to identify genetic variants associated with each condition and determine which variants are shared or unique.

Shared Genetic Factors

One of the key findings was that a substantial portion of the genetic variants linked to autism are also associated with ADHD, and vice versa. Specifically:

• About 37.5% of genetic variants linked to autism were also associated with ADHD
• About 19.6% of genetic variants linked to ADHD were also associated with autism

This provides strong evidence for shared genetic factors underlying both conditions. Some of the genes identified as potentially being involved in both autism and ADHD include:

• XRN2
• SORCS3
• PTBP2
• NKX2-4
• MANBA
• DPYD

The researchers also discovered two novel genes - INSM1 and PAX1 - that may play a role in both conditions. INSM1 is known to be important for brain development, specifically in the formation of neurons and neuroendocrine cells during fetal development.

Condition-Specific Genes

While there was significant genetic overlap, the study also found genes that appear to be uniquely associated with either autism or ADHD. For autism, two genes - XRN2 and NKX2-4 - were identified as potentially autism-specific. For ADHD, 36 genes were flagged as potentially ADHD-specific.

This suggests that while autism and ADHD share some common genetic risk factors, there are also distinct genetic pathways involved in each condition. Further research into these condition-specific genes may help explain the unique features of autism versus ADHD.

Brain Expression Patterns

Interestingly, when the researchers looked at where in the brain the identified genes are typically expressed, they did not find any clear patterns. The genes associated with autism and ADHD were not preferentially expressed in any particular brain regions or at any specific developmental stages. Instead, they tended to be expressed throughout the brain and across the lifespan, including in adulthood.

This suggests the genetic risk for these conditions may involve subtle alterations in brain function and development that occur broadly, rather than being localized to specific regions or timepoints.

Bidirectional Relationship

The researchers also used a technique called Mendelian randomization to explore whether having more traits of one condition directly increases risk for the other. They found evidence for a bidirectional relationship:

• Having more autism traits was associated with increased risk of ADHD
• Having more ADHD traits was associated with increased risk of autism

This bidirectional relationship held true even when accounting for genes that directly overlap between the conditions. However, the researchers caution that other factors could potentially explain this finding, such as unmeasured genetic or environmental influences that increase risk for both conditions.

Implications and Future Directions

This study provides important new insights into the genetic underpinnings of autism and ADHD, and why these conditions so often co-occur. Key takeaways include:

• There are substantial shared genetic factors, with about 20-35% of risk genes overlapping
• Each condition also has unique genetic contributors
• The implicated genes are expressed broadly in the brain across development
• There may be a bidirectional relationship, where traits of one condition increase risk for the other

Understanding these shared and unique genetic pathways could potentially lead to new treatment targets that address symptoms common to both conditions. It may also help explain why some individuals show features of both autism and ADHD.

However, many questions remain. The genes identified so far likely only account for a small portion of the total genetic risk. Larger studies are needed to uncover more of the complex genetics involved. Additionally, environmental factors also play an important role and need to be studied alongside genetics.

Future research should also explore how specific genetic variants relate to particular symptoms or traits, rather than broad diagnostic categories. This could provide a more nuanced understanding of how genetics shape neurodevelopmental outcomes.

Conclusions

• Autism and ADHD have substantial genetic overlap, helping explain why they often co-occur
• Each condition also has unique genetic risk factors
• Implicated genes are expressed broadly in the brain across development
• More autism traits may increase ADHD risk and vice versa, but more research is needed
• Understanding these genetic relationships could lead to new treatment approaches