Genetic candidates for ADHD

The articles in this section organize more than 300 ADHD gene candidates according to their possible pathway of action on ADHD. This article is organized according to the best known and most obvious mechanisms of action, starting with dopamine, noradrenaline and other neurotransmitters. The gene candidates have each been categorized in this ranking system under the one of their (and known) mechanisms of action that is most closely associated with ADHD.
However, the extent and intensity of the influence of the various mechanisms of individual genes on ADHD is often not known, which significantly limits the resilience of the classification. For example, we classified genes that are linked to dopamine as long as there was no positive evidence that another pathway of the gene has a greater influence on ADHD. For example, a dopaminergic pathway was sufficient for us to classify it under dopamine, even if other pathways are known that also correlate with the development of ADHD. This is naturally very abbreviated. We hope that we will gradually be able to add further information that will improve the classification of the genes.

So far, the overview has primarily served as an orientation as to which mechanisms of action are served by a number of ADHD candidate genes, which provides a certain indication of a connection between the pathway and the development of ADHD.
However, we know of no other publication that attempts to organize the ADHD gene candidates according to mechanisms of action on ADHD in such a comprehensive way: We therefore hope that this presentation, despite its limitations, might give an interesting impression of the probable and possible pathways of action in the development of ADHD.

In the following article, we collect gene candidates for which we have not yet been able to determine how they can influence the development of ADHD.

One study found 560 genes and 6 miRNAs that were expressed differently in people with ADHD than in those without the disorder.¹ Changes in gene expression cause a deviation in the activity of the gene and thus the effects mediated by it (e.g. activity of a receptor, transporter, protein). Other studies found many other possible genes, so that a four-digit number of candidate genes can currently be assumed.
An interesting study of 1033 people with ADHD versus 950 non-affected people came to a result that achieved diagnostically relevant values of accuracy (0.9018), AUC (0.9570), sensitivity (0.8980) and specificity (0.9055) by considering the combined effect of multiple variants with insignificant P-values and analyzing them using deep learning (“KI”). The study found 96 candidate genes, of which only 14 genes had been reported in previous studies related to ADHD.²

The Chinese ADHDgene database lists genes relevant to ADHD.³ However, it does not appear to have been updated since 2014.

Some of the genes listed below cause rare (orphan) diseases in the event of a genetic defect. For example, the SYNE1 gene (one of the 560 genes from the study by Nuzziello et al) causes SYNE1 ataxia in 20 out of 100,000 people, i.e. it has a prevalence of 0.02%.⁴ The following thought experiment may give an impression of the contribution of individual genes to ADHD: If all of the 560 genes named as candidate genes for ADHD caused such a rare orphan Disorder (each of which would be associated with ADHD symptoms), and if each gene alteration occurred alone, the sum of these 560 genes would already give a prevalence of 11.2%, which would equal or exceed the prevalence of ADHD.

Gene databases:

Genetic candidates in ADHD means possible genes that may be involved in the development of ADHD.
We have started to subdivide the genes according to whether they influence already known neurophysiological mechanisms for ADHD. This is a mammoth task that may take years to complete.
Copy number variants as well as miRNA and RNA, which influence the expression of genes, are presented separately.