Locus-specific DNA methylation changes and phenotypic variability in children with attention-deficit hyperactivity disorder

Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD. DNA extracted from peripheral blood was used to examine methylation between 25 children exposed, and 22 children not exposed to maternal smoking during pregnancy. Three genes (AHRR, CYP1A1, GFI1) were selected based on previous results observed in the general population. Regression analysis was conducted between methylation levels in these candidate genes and: (a) total number of ADHD and CD symptoms; (b) birth weight. Significant differences in methylation were observed in each of the candidate genes between children exposed and not exposed to maternal smoking during pregnancy. Methylation at the selected sites showed significant association with specific phenotypes. Significant correlations were observed between methylation within AHRR and number of CD symptoms; GFI1 and number of ADHD symptoms and GFI1 and birth weight. These initial results may have important clinical implications if confirmed in a larger independent sample.