Abstract
BACKGROUND: Established psychosocial risk factors increase the risk for experimentation among Mexican origin youth. Now, we comprehensively investigate the added contribution of select polymorphisms in candidate genetic pathways associated with sensation seeking, risk taking, and smoking phenotypes to predict experimentation. METHODS: Participants (N = 1,118 Mexican origin youth) recruited from a large population-based cohort study in Houston, TX, provided prospective data on cigarette experimentation over 3 years. Psychosocial data were elicited twice-baseline and final follow-up. Participants were genotyped for 672 functional and tagging variants in the dopamine, serotonin, and opioid pathways. RESULTS: After adjusting for gender and age, with a Bayesian False Discovery Probability set at 0.8 and prior probability of 0.05, six gene variants were significantly associated with risk of experimentation. After controlling for established risk factors, multivariable analyses revealed that participants with six or more risk alleles were 2.25 [95% confidence interval (CI), 1.62-3.13] times more likely to have experimented since baseline than participants with five or fewer. Among committed never-smokers (N = 872), three genes (OPRM1, SNAP25, HTR1B) were associated with experimentation as were all psychosocial factors. Among susceptible youth (N = 246), older age at baseline, living with a smoker, and three different genes (HTR2A, DRD2, SLC6A3) predicted experimentation. CONCLUSIONS: Our findings, which have implications for development of culturally specific interventions, need to be validated in other ethnic groups. IMPACT: These results suggest that variations in select genes interact with a cognitive predisposition toward smoking. In susceptible adolescents, the impact of the genetic variants appears to be larger than committed never-smokers.