Genetic candidates for ADHD - Introduction

The articles in this section organize more than 500 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 unknown, 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.

We have collected gene candidates for which we have not yet been able to determine how they can influence the development of ADHD in a separate article.

A study from 2019 found 560 genes and 6 miRNAs with aberrant expression in ADHD.¹ A study from 2024 found 1057 ADHD gene candidates.² Another study from 2024, which integrated GWAS, sQTL and eQTL summary data from 14 brain tissues and used four Mendelian randomization methods to determine the causal effects of alternative splicing events and gene expressions on ADHD, identified the expression of 866 genes and the alternative splicing events of 966 genes as significant causal effects on ADHD. From this, tissue-specific and cross-tissue gene networks were determined and 106 regulatory signaling pathways were identified in which DNAm influence ADHD through specific transcriptional processes.³
The largest GAWAS to date identified 7,600 common gene variants that have an influence on ADHD. There were 10,300 for ASD, 9,600 for schizophrenia, 11,700 for depression and 8,600 for bipolar Disorder.⁴

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 have found many other possible genes, so that a four-digit number of candidate genes can currently be assumed.
An interesting study of 1,033 people with ADHD and 950 non-affected people arrived at 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.⁵

The Chinese ADHDgene database lists genes relevant to ADHD.⁶ However, it does not appear to have been updated since 2014.

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.