Attention deficit/hyperactivity disorder (ADHD) is a behavioural disorder that affects about 5% of children and adolescents and 2.5% of adults. Despite an estimated heritability of 70-80%, genome-wide association studies (GWAS) have so far failed to identify any common genetic variants robustly associated with ADHD. Now, a study in Nature Genetics reports 12 genome-wide significant loci for ADHD, which implicate biologically informative genes as important to its aetiology.

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GWAS were conducted on 12 European, North American and Chinese cohorts that comprised 20,183 individuals with ADHD and 35,191 controls. Meta-analysis of these GWAS identified 304 genetic variants (from a total of 8,047,421) that exceeded the genome-wide significance threshold (P < 5 × 10−8). These variants represented 12 distinct loci and the associations were consistent across all 12 cohorts. The single-nucleotide polymorphism (SNP) heritability (h2SNP) was estimated to be 0.22, which is consistent with other complex traits and with figures from previous smaller ADHD studies (h2SNP = 0.1–0.28) and GWAS for other neurodevelopmental disorders, such as schizophrenia (h2SNP = 0.23–0.26).

Several of the 12 significant loci were shown to be in, or close to, genes involved in neurodevelopmental processes relevant to ADHD. For example, the FOXP2 gene in the chromosome 7 locus is involved in synapse formation and the development of speech and learning; problems with language development and learning are common in ADHD. Similarly, the chromosome 12 locus spans DUSP6, whose possible role in regulating dopamine levels at synapses is consistent with the purpose of ADHD medications that act to increase the availability of synaptic dopamine.

Of 219 phenotypes tested for pairwise genetic correlation, 43 had significant genetic overlap with ADHD. In most cases, these correlations were supported by multiple related phenotypes. For example, positive correlations were observed for major depressive disorder, depressive symptoms and neuroticism. Negative correlations were observed for years of schooling and human intelligence. This genetic overlap with epidemiologically relevant phenotypes lends weight to the view that ADHD is the extreme expression of one or more continuous heritable traits.

ADHD is the extreme expression of one or more continuous heritable traits

Thus, further analysis of the loci and pathways implicated by this study might provide insight into the aetiology of not only ADHD but also other, related disorders.