Epigenetics of hyperactivity disorder
ADHD is one of the most common heritable psychiatric conditions with an onset during childhood. Children with ADHD demonstrate inattention and hyperactivity-impulsivity that interferes with functioning or development. In addition, they are at high risk of developing antisocial behaviour, substance abuse and other psychiatric disorders, as well as difficulties in their education and social integration. Despite evidence for a familial liability of ADHD, there is no clear genetic association and the precise genetic background of ADHD is still unknown. Scientists on the EU-funded EPIMEN (Epigenetics in mental disorders: The role of imprinting and methylation patterns in attention deficit hyperactivity disorder (ADHD)) project studied the epigenetics of ADHD. They performed genome-wide scans to identify candidate genetic loci with parent of origin effects and determine the methylation patterns of such loci in ADHD. The study included a large sample of trios, families consisting of patients with a confirmed diagnosis of ADHD and two living biological parents with or without the condition. Trios from the Psychiatric Genomics Consortium and the Norwegian Mother Child cohort were included but overall no genome-wide significant hit was observed. With respect to the methylation pattern in ADHD, 70 adult ADHD cases and 58 controls were successfully genotyped. The results from this analysis will portray epigenetic alterations associated with an increased susceptibility to ADHD. Considerable effort went towards the development of methodology for the log-linear modelling of parent of origin effects (POE) in continuous traits such as ADHD. This allowed researchers to evaluate various aspects and confounders in POE such as association, maternal effect and imprinting. Given that ADHD is linked to deficits in the functioning of several brain areas, study results will disclose the association of epigenetic variations with these observable symptoms. Complex traits such as ADHD are likely to have a plethora of genes with small to moderate effects, emphasising the need for the elucidation of the molecular architecture of the disorder.
Keywords
Epigenetics, attention deficit hyperactivity disorder, EPIMEN, methylation, parent of origin effects
