in ADHD subjects with the A-allele compared to controls with the same allele (t138=2.15, p=0.03). Since ADHD severity may change over time, subjects were stratified based on the presence or absence of ADHD symptoms at follow-up which again revealed a strong interaction between the CREM polymorphism and ADHD persistence (F2,136=4.35, p=0.02, Fig. 4d). Specifically, past drug use was significantly elevated in A-allele carriers with persistent symptomology when compared to controls (t136=2.61, p=0.02), but there was no difference between those in remission and controls (t136=0.69, p=0.49). Similar interactions were observed in a larger independent population of 1054 adolescents from IMAGEN29. After correcting for gender, age and ethnicity, there were significant ADHD × rs12765063 interactions with respect to the number of individuals reporting any lifetime use (β=0.93, Χ2=4.57, p=0.03, Supplementary Fig. 8b) and the amount of use by those reporting any use (F1,361=3.96, p=0.05, Supplementary Fig. 8c).
