Abstract
PURPOSE: Polygenic risk scores (PRSs) for smoking behavior largely fail to consider the demonstrated developmental change in genetic influence over age and stage of smoking behaviors. Additionally, few studies have examined how stage-specific smoking PRSs (e.g. for initiation vs. smoking heaviness) generalize to other stages of risk. The current study examines the stability of PRS effects over age, and how specifically calibrated PRSs associate with other smoking phenotypes. METHODS: 7228 participants were from the National Longitudinal Study of Adolescent to Adult Health, who had calculated PRSs for two smoking phenotypes, Centers for Disease Control and Prevention (CDC) smoking initiation status, and cigarettes per day (CPD). Four time-varying effects models estimated associations between both PRSs and four smoking phenotypes (CDC status, cigarettes/day on smoking days, any past-30 day smoking, and past-30 day daily smoking) over adolescence and young adulthood. FINDINGS: The time-varying effects models demonstrated that both PRSs significantly associated with all four phenotypes age. PRS effects were similar, in both odds ratios and the overlap of 95 % confidence intervals. There were increases in PRS associations with quantity of smoking over age, and a decrease in PRS effects over age for the CDC smoking status phenotype over early to late adolescence. CONCLUSIONS: Smoking PRSs can be robust predictors of smoking behavior over age. However, the lack of differentiation between specific PRSs and multiple smoking phenotypes, as well as the added contribution of both PRSs to explaining genetic variance, indicates a need to reconceptualize phenotypic measurement used to calibrate smoking PRSs.