Polygenic risk scores for nicotine use and family history of smoking are associated with smoking behaviour

Introduction Formal genetics studies show that smoking is influenced by genetic factors; exploring this on the molecular level can offer deeper insight into the etiology of smoking behaviours. Methods Summary statistics from the GWAS and Sequencing Consortium of Alcohol and Nicotine (GSCAN) Consortium were used to calculate polygenic risk scores (PRS) in a sample of ~2,200 smokers/never-smokers. The association of PRS for Smoking Initiation (i.e. Lifetime Smoking; SI-PRS) with smoking status, and PRS for Cigarettes per Day (CpD-PRS) and Smoking Cessation (SC-PRS) with Fagerstrom Test for Nicotine Dependence (FTND) score were examined, as were distinct/additive effects of parental smoking on smoking status. Results SI-PRS explained 6.65% of variance (Nagelkerke-R2) in smoking status (p=1.71x10-24). In smokers, CpD-PRS (R2=3.15%, p=1.82x10-8) and SC-PRS (R2=2.01%; p=7.18x10-6) were associated with FTND score. Parental smoking alone explained R2=3.06% (p=2.43x10-12) of smoking status, and 1.39% when added to the most informative SI-PRS model (total R2=8.04%). Conclusion These results show the potential utility of molecular genetic data for research investigating smoking prevention. The fact that PRS explains more variance than family history highlights progress from formal to molecular genetics; the overlap and increased predictive value when using both suggests the importance of combining these approaches. Implications: This study underlines the value of using PRS to predict smoking status/behaviour. It highlights the importance of molecular genetic methods in research investigating smoking prevention and points to the necessity of combining family history and molecular genetic data.