PHG Foundation | Large rare copy number variants implicated in ADHD

Large rare copy number variants implicated in ADHD
30 September 2010 | By Dr Caroline Wright and Dr Gurdeep Sagoo | Research article

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder influenced, like all common complex conditions, by both multiple genetic and environmental factors. It is believed to be the most common behavioural disorder in the UK, estimated to affect 3-9% of school-aged children and young people (see NHS Choices website).

A new study published online in The Lancet has investigated whether rare large copy number variants (CNVs) across the genome are present more often in individuals with ADHD compared with controls, and whether these regions overlap with other neurodevelopmental disorders such as autism and schizophrenia [Williams NM, et al. Lancet (2010) doi:10.1016/S0140-6736(10)61109-9]. The UK-based study involved a genome-wide analysis of large, rare CNVs – those greater than 500kb in size and present in less than 1% of the population – in 410 children with ADHD and a further 1156 controls.

Full data were available for 366 cases and 1047 controls, with 57 CNVs (15.6%) identified in 50 cases (14%) and 78 CNVs (7.5%) in 75 controls (7%), indicating an enrichment of large CNVs in children with ADHD. Twelve of these cases also had DNA from both parents available for analysis. Of the 15 CNVs identified in these twelve cases, six were inherited from the mother, five from the father, and four were novel. The CNVs identified showed considerable overlap with regions implicated in both autism and schizophrenia. Duplications on chromosome 16 were also identified more often that expected in the cases, and this finding was replicated in an independent Icelandic set of 825 patients with ADHD and 35,243 population controls.

Comment: Despite being highly heritable, the underlying causes of ADHD are still poorly understood. Whilst some strongly believe that environmental factors such as diet, poor parenting, and fetal exposure to maternal smoking or maternal stress are largely to blame, this study uncovers clues to the genetic basis of ADHD. As with other common complex diseases, there is no simple cause. Genetic factors, environmental factors, as well as an interaction between the two, all contribute to disease occurrence to varying degrees.

As our understanding is aided by advances in technology (see previous news), more rare CNVs are being identified associated with behavioural disorders, such as ADHD and autism (see previous news). In some individuals, these findings may explain a large part of the disease (see previous news), whilst in others, genetic factors may play a much smaller role.

Keywords: Disease Susceptibility (Genetic
PHG Foundation | Large rare copy number variants implicated in ADHD