An Adolescent Substance Prevention Model Blocks the Effect of CHRNA5 Genotype on Smoking During High School

Prevention intervention programs reduce substance use, including smoking, but not all individuals respond. We tested whether response to a substance use prevention/intervention program varies based upon a set of five markers (rs16969968, rs1948, rs578776, rs588765, and rs684513) within the cluster of nicotinic acetylcholine receptor subunit genes (CHRNA5/A3/B4).

Participants (N = 424) were randomly assigned to either control condition, or a family-based intervention in grade 6 and a school-based drug preventive intervention in grade 7. Smoking in the past month was assessed in grades 9-12 using a four-point scale (0 = never smoked, 1 = smoked but not in last month, 2 = one or a few times, 3 = about once a week or more).

There was a main effect of both the intervention (b = -0.24, P < .05) and genotype at rs16969968 (b = 0.14, P < .05) on high school smoking. Using dummy coding to allow for nonlinear effects, individuals with the A/A genotype smoked more often than those with G/G (b = 0.33, P < .05). A genotype × intervention effect was found with reduced smoking among those with A/A and G/A genotypes to levels similar to those with the G/G genotype (G/G vs. A/A: b = -0.67, P < .05; A/G vs. A/A: b = -0.61, P < .05; G/G vs. A/G ns). Results were nonsignificant for the other four markers.

Preventive interventions can reduce the genetic risk for smoking from rs16969968.