SU6: SYNERGISTIC EFFECT OF COMT AND KIAA0319 GENES IN MODULATING ADHD BEHAVIORS

Abstract

Background ADHD and Learning Disorder (LD) are complex disorders with genetic and environmental determinants. Twenty to 30% of the children with ADHD have an associated LD. These problems usually persist into adolescence and are associated with chronic academic underachievement and failure to complete school. Hypothesis: Given the evidence for overlapping heritability between ADHD and LD, we hypothesize KIAA0319, a gene associated with LD, may interact with genes that have shown to be implicated in ADHD. As proof of concept, we have selected the COMT gene because of the well-documented role of its Val/Met polymorphism in modulating dopamine transmission in the frontal cortex. We also anticipated that the interaction between these two genes would be more evident in the school environment. Methods 400 children with ADHD (9–12 years old) were included in a double-blind placebo controlled study with methylphenidate. Teachers and parents were asked to evaluate the child s behavior at baseline, placebo, and MPH weeks using the appropriate version of Conners’ scale. The association between genotypes and ADHD behaviors were tested using repeated measure ANOVA, the two genes were the between-subject factors and the behaviors under the three experimental conditions (EC), were the within-subject factor. Results A highly significant 3-way interaction (KIAA0319⁎COMT⁎EC) was revealed in two SNPs of the KIAA0319 gene (rs4504469 p= 0.006 and rs7766230 p= 0.004) only according to teachers. By stratifying the children according to their COMT genotypes, we found that within the Met/Met genotype group, there were no significant differences in Conner s-T scores at baseline and on Placebo. However, significantly different patterns of response to MPH between KIAA0319 genotype groups were observed. Discussion This is the first study identifying an interaction between a gene involved in LD and a gene implicated in ADHD. This might help to individualize treatments for children with comorbid ADHD and learning disorders.