1.4.1 Genetics and ADHD

To date, two main methods have been used to identify specific genes that may play a role in ADHD:

• Linkage studies are genome-wide searches to identify any genetic variation that is shared more often than expected among ADHD family members. At present these studies have yet to provide any definitive answers. However, linkage studies can only detect genetic variants that have a large effect on the subject of interest, in this case expression of ADHD. Therefore, the lack of definitive findings from this type of study could mean that no single gene exerts a large impact on expression of ADHD. Instead the genetic component of ADHD could be driven by many genes each exerting a much smaller influence, which in combination have an impact on the expression of ADHD.
• Candidate gene studies allow researchers to choose genes based on neurobiological studies or theoretical considerations and then to directly compare these in different groups of people. This comparison can be done using case-control or family-based studies. In case-control studies the frequency of a gene is looked at in individuals with a condition and those without. In a family-based study, the comparison is between family members, normally parents and their children.

To date, these studies have identified several candidate genes that may be important in ADHD, although each only has a small association with the condition, again supporting the view that ADHD may involve many genes each exerting a small effect (Faraone and Larsson, 2019). Most of the genes identified in these studies are linked to the neurotransmitter dopamine (Gizer et al., 2009) which will be considered later in this course.

Evidence from early genetic studies has indicated that ADHD is unlikely to be caused by a single, or even a few genes, but rather a combination of many genes acting together. Genetic researchers are starting to use genome-wide association studies (GWAS), which look at the entire genome to detect common genetic variants within groups of individuals with the same condition. GWAS look at hundreds of thousands of single nucleotide polymorphisms (SNPs, pronounced snips). A SNP is a change to a single nucleotide in a sequence of DNA.

Early GWAS failed to identify any variants associated with ADHD but a recent meta-analysis (a type of study that pools results across several different studies) of several GWAS has proved more successful.

In this case, the meta-analysis included 20 183 individuals with ADHD and 35 191 control participants, and identified 12 possible SNPs in the genome (Demontis et al., 2017). Interestingly, none of the 12 SNPs identified correspond to the candidate genes found in previous studies. However, the patterns found in the data confirm that the heritability of ADHD is likely to be due to polygenic (multiple gene) effects, each having a very small influence, which in combination can confer a genetic risk for ADHD. Therefore, to date, while studies have not consistently identified specific genes involved in ADHD, there is some consensus on the way in which genetic influence arises.

So far, this section has focused on the genetic risk associated with ADHD, but heritability of ADHD is not 100%, so other factors must play a role. You will now turn your attention to environmental factors.