Aim: This study tests whether polygenic risk scores (PRSs) for nicotine metabolism predict smoking behaviors in independent data.
Materials & methods: Linear regression, logistic regression and survival analyses were used to analyze nicotine metabolism PRSs and nicotine metabolism, smoking quantity and smoking cessation.
Results: Nicotine metabolism PRSs based on two genome wide association studies (GWAS) meta-analyses significantly predicted nicotine metabolism biomarkers (R2 range: 9.2-16%; minimum p = 7.6 × 10-8). The GWAS top hit variant rs56113850 significantly predicted nicotine metabolism biomarkers (R2 range: 14-17%; minimum p = 4.4 × 10-8). There was insufficient evidence for these PRSs predicting smoking quantity and smoking cessation.
Conclusion: Results suggest that nicotine metabolism PRSs based on GWAS meta-analyses predict an individual's nicotine metabolism, so does use of the top hit variant. We anticipate that PRSs will enter clinical medicine, but additional research is needed to develop a more comprehensive genetic score to predict smoking behaviors.
Keywords: CYP2A6; nicotine metabolism; polygenic risk scores; smoking cessation.