🧬 How Rare Genetic Variants Contribute to Autism and ADHD

Citation:

Duan, J., Grove, J., Demontis, D., Satterstrom, F. K., Fu, J. M., Carey, C. E., Sanders, S. J., Devlin, B., Roeder, K., Buxbaum, J., Robinson, E., Talkowski, M., Neale, B. M., Daly, M., & Børglum, A. (2025). Dissecting the contribution of rare coding variants to risk of autism and ADHD. European Neuropsychopharmacology, 99(S1), 96–97. https://doi.org/10.1016/j.euroneuro.2025.08.184

Overview

This study looked at how rare changes in genes contribute to autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD)—two conditions that often overlap. Researchers wanted to understand whether these rare genetic changes affect both disorders in similar ways and whether some genes increase risk for both.

Background

ASD and ADHD are both highly heritable, meaning genetics play a major role in their development. Past studies showed that rare protein-truncating variants—genetic changes that disrupt how a gene works—are more common in people with either disorder.

This research expanded on earlier work by analyzing a much larger group to see:

1. How much rare variants contribute to overall genetic risk
2. How strongly ASD and ADHD share these rare genetic influences
3. Which specific genes are involved

Methods

• Sample: 25,208 people from the Danish iPSYCH project
• 7,119 with autism only
• 5,598 with ADHD only
• 3,794 with both autism and ADHD
• 8,697 without either condition (controls)
• Researchers studied each person’s exome—the protein-coding part of the genome—to identify rare harmful mutations.
• They compared genetic patterns between groups and tested how much these rare variants explain the risk for each disorder.

Results

• All three clinical groups (autism, ADHD, and both) had a similar increase in rare damaging variants compared to controls.
• There were no major genetic differences between autism-only and ADHD-only groups, suggesting strong genetic overlap.
• Rare variants explained about 1.8% of autism risk and 3.2% of ADHD risk—a small but meaningful share of each condition’s heritability.
• The genetic correlation between autism and ADHD was 0.46, almost identical to previous results from common genetic variants, showing consistency across genetic types.
• Researchers identified eight specific genes associated with both conditions:
• MAP1A, a previously known shared gene
• Seven new genes, several already linked to neurodevelopmental disorders, and one never before connected to either condition.

Discussion

The findings confirm that autism and ADHD share significant rare genetic roots, reinforcing earlier evidence that the two conditions have overlapping biology.

At the same time, researchers note the need to study what’s distinct about each disorder and to explore whether genetic effects differ between males and females.

These results highlight that both common and rare genetic variations contribute to a shared neurodevelopmental spectrum.

Empowering Takeaways

• Autism and ADHD share deep biological links. Many of the same rare genetic factors influence both conditions.
• Rare doesn’t mean unimportant. Even though these variants are uncommon, their effects can be significant.
• Genetics is only part of the story. While genes create vulnerability, environment and experience shape how traits appear.
• Shared genes help explain overlap. Understanding these connections could lead to more accurate diagnoses and more tailored supports in the future.