Children with ADHD Differ Genetically from People Who Are Diagnosed as Adults

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Five percent of all school children in Denmark show symptoms of ADHD. For adults, it is around three percent. ADHD is a neurodevelopmental disorder with onset in childhood. Two-thirds of children who are diagnosed with ADHD continue to have ADHD as adults. In other cases, ADHD is not diagnosed until adulthood.

Researchers from the national psychiatry project iPSYCH have studied the genetic differences between people diagnosed during childhood and people diagnosed as adults.

“We’ve found that the genetic architecture differs depending on how old you are when you get an ADHD diagnosis,” says Associate Professor Ditte Demontis who is behind the study.

Less hyperactivity in adults

Approximately 74 percent of the risk of being diagnosed with ADHD is caused by genetics. The genetics that cause ADHD are ‘polygenic’, which means that ADHD is caused by several genetic variants in the genome, each of which contributes slightly to the risk of developing the disease. Genetic architecture is the overall term for all variants in the genome that contribute to ADHD.

In the new study, researchers analysed the genetic architecture of people diagnosed with ADHD as children and people diagnosed with ADHD as adults.

By comparing these results with the results of other large-scale genetic studies of autism and depression, the researchers discovered that the genetic architecture in children diagnosed with ADHD overlaps with autism significantly more than the genetic architecture of people diagnosed as adults. 

For individuals diagnosed with ADHD as adults, on the other hand, the genetic architecture overlaps with the genetics of depression to a much higher degree than those who are diagnosed as children. This means that people diagnosed with ADHD as adults have an increased risk of depression due in part to genetic risk factors.

The researchers also found that the genetic architecture of people diagnosed with ADHD as adults had a lower load of genetic variants involved in hyperactivity and inattention issues than people who are diagnosed with ADHD during childhood.

“In other words, people who are diagnosed with ADHD as adults are generally less genetically predisposed to be hyperactive and inattentive. This result may help to explain why the time of diagnosis occurred later in life for this particular group of people with ADHD,” explains Ditte Demontis.

Overall, these results suggest that there are differences in the underlying genetic architecture of ADHD depending on when you are diagnosed. The results of the study provide new information on which illnesses you have an increased genetic risk of developing depending on when in life you receive your ADHD diagnosis.

Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD).

We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls.

We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups.

Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes.

Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants.

Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

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