Attention-Deficit/Hyperactivity Disorder Genomics: Update for Clinicians

Josephine Elia, Jillan Sackett, Terri Turner, Martin Schardt, Shih-Ching Tang, Nicole Kurtz, Maura Dunfey, Nadia A. McFarlane, Aita Susi, David Danish, Alice Li, Jenelle Nissley-Tsiopinis, Karin Borgmann-Winter

Attention deficit, hyperactivity disorder (ADHD) is familial and highly heritable. Several candidate genes involved in neurotransmission have been identified, however these confer minimal risk, suggesting that for the most part, ADHD is not caused by single common genetic variants. Advances in genotyping enabling investigation at the level of the genome have led to the discovery of rare structural variants suggesting that ADHD is a genomic disorder, with potentially thousands of variants, and common neuronal pathways disrupted by numerous rare variants resulting in similar ADHD phenotypes. Heritability studies in humans also indicate the importance of epigenetic factors, and animal studies are deciphering some of the processes that confer risk during gestation and throughout the post-natal period. These and future discoveries will lead to improved diagnosis, individualized treatment, cures, and prevention. These advances also highlight ethical and legal issues requiring management and interpretation of genetic data and ensuring privacy and protection from misuse.