Research ArticleAttention Deficit Hyperactivity Disorder

Rare Copy Number Variation Discovery and Cross-Disorder Comparisons Identify Risk Genes for ADHD

Science Translational Medicine  10 Aug 2011:
Vol. 3, Issue 95, pp. 95ra75
DOI: 10.1126/scitranslmed.3002464

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Complexities of Cognition: The Case of ADHD

As for autism and schizophrenia, the closer we look at attention deficit hyperactivity disorder (ADHD), the more complicated it seems. Found in 4% of children, this syndrome of attention, hyperactivity, and impulsiveness is highly heritable, yet we know only a few of the responsible genetic variants. Here, Lionel et al. assessed a particularly well-defined population of 248 children with ADHD, plus many of their parents, for extra copies or deletions of genes. The 306 rare copy number variations (CNVs) found in these individuals were of various kinds—only 1.7% were de novo mutations in brain-specific genes, 7.7% were clearly inherited and occurred in genes known to be associated with ADHD or defined new culprit genes, and several were in genes already implicated in other disorders such as autism.

To take a closer look at possible genes that confer risk for more than one developmental disorder, the authors examined the CNVs in a separate group of patients with autism. In four autism patients and two of the patients with ADHD, a cluster of rare disorder-associated CNVs occurred on chromosome 9 in and around two genes: ASTN2, necessary for mammalian brain development, and TRIM32, a neuronal stem cell–associated gene. This region has also been associated with CNVs in bipolar disorder, intellectual disability, and schizophrenia.

In all, the authors found rare inherited CNVs at sites that had been previously implicated in ADHD or in other neurodevelopmental disorders in 8% of the individuals with ADHD. Their results implicate common genes and pathways for several neuropsychiatric disorders, which is consistent with the common clinical co-occurrence of ADHD with other such conditions.


  • Citation: A. C. Lionel, J. Crosbie, N. Barbosa, T. Goodale, B. Thiruvahindrapuram, J. Rickaby, M. Gazzellone, A. R. Carson, J. L. Howe, Z. Wang, J. Wei, A. F. R. Stewart, R. Roberts, R. McPherson, A. Fiebig, A. Franke, S. Schreiber, L. Zwaigenbaum, B. A. Fernandez, W. Roberts, P. D. Arnold, P. Szatmari, C. R. Marshall, R. Schachar, S. W. Scherer, Rare Copy Number Variation Discovery and Cross-Disorder Comparisons Identify Risk Genes for ADHD. Sci. Transl. Med. 3, 95ra75 (2011).