Nicotinic receptor gene variants interact with attention deficient hyperactive disorder symptoms to predict smoking trajectories from early adolescence to adulthood

Abstract

Objective To examine the association of single nucleotide polymorphisms (SNPs) of the CHRNB3 (rs13280604) and CHRNA6 (rs892413) nicotinic acetylcholine receptor (nAChR) genes and symptoms of attention deficit hyperactivity disorder (ADHD) in predicting smoking patterns from early adolescence to adulthood. Method A longitudinal cohort of 1137 unrelated youths from the National Longitudinal Study of Adolescent Health provided responses to four surveys from Waves I to IV, and a genetic sample in Wave III. Growth mixture modeling was used to identify smoking patterns and to assess the effects of the two SNPs and ADHD symptoms on cigarette use over time. Results There were significant main effects of ADHD symptoms and CHRNA6 variants in predicting the number of cigarettes smoked and the pattern of use over time, respectively. There were no main effects of the CHRNB3 variants. However, a significant CHRNB3 variant × ADHD symptom interaction was observed, such that individuals with elevated ADHD symptoms and a particular CHRNB3 variant were at increased risk of cigarette use over time. Conclusions These findings demonstrate that a SNP in a nicotinic receptor gene may interact with ADHD symptoms to link with increased cigarette use across adolescence and young adulthood. Unique associations between specific variants and patterns of ADHD symptoms were identified which may be useful for targeting prevention efforts to individuals at greatest risk for cigarette smoking.

Methylomic analysis of salivary DNA in childhood ADHD identifies altered DNA methylation in VIPR2

“…Thus, a third more focused hypothesis generated by those explorations involves epigenetic modulation of cholinergic or nicotinic receptor functioning. This focus may be particularly intriguing in light of the recent interest in those receptors' role in prefrontal cortical function, impulsivity, and attention (Lee, Fuemmeler, McClernon, Ashley-Koch, & Kollins, 2013;Ohmura, Tsutsui-Kimura, & Yoshioka, 2012;Sterley, Howells, & Russell, 2014;Wallace & Bertrand, 2013), recent genetic findings related to ADHD and cholinergic receptor genes (Williams et al, 2012), and interest in the role of nicotinic receptor intervention as an effective and novel treatment target for ADHD in animal and human trials (Bain et al, 2012;Potter, Dunbar, Mazzulla, Hosford, & Newhouse, 2014). ADHD status in the children from whom saliva was analyzed in this study was very well characterized.…”

Nicotine Addiction and Psychiatric Disorders

“…While undoubtedly many factors contribute to this relationship, increasing evidence suggests that differences in attention processes and ADHD symptoms may be related to genetic variants in genes encoding nicotinic receptor subunits. Lee, Fuemmeler, McClernon, Ashley-Koch, and Kollins (2013) found a significant interaction between single nucleotide polymorphisms of CHRNB3 and ADHD where the AA variant and the ADHD symptom of inattention were associated with greater increase in the level of cigarette smoking across adolescence. The study also reported differences in cigarette smoking associated with variants of CHRNA6.…”

Crucial roles of the CHRNB3–CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research

“…Apart from early-subjective responses to tobacco, there exist many other ND-related phenotypes where the CHRNB3–CHRNA6 gene cluster may play an important role, such as smoking status (never smoking versus ever smoking), 35 smoking trajectories from early adolescence to adulthood, 45 and various ND endophenotypes such as ‘novelty seeking' 53 or ‘drive.' 37 In addition, smoking cessation is of great interest, because it is the ultimate goal of studying tobacco addiction and any other smoking-related phenotypes.…”