DNA methylation (DNAm), one of the main forms of epigenetic modification, has been linked to tobacco exposure and smoking-induced diseases (Gao et al., 2015). Epigenome-wide association studies (EWAS) have shown reproducible associations between smoking and altered DNAm at thousands of cytosine-phosphate-guanine (CpG) sites which, when located at functionally important genomic regions1 , regulate gene transcription (Joehanes et al., 2016; Sikdar, Joehanes, Joubert, Xu, London, et al., 2019). However, it is not clear from EWAS whether observed differences in methylation at CpG sites between smokers and non-smokers are caused by cigarette smoking or if they are downstream consequences of related comorbidities and environmental factors that are highly correlated with smoking behavior. Moreover, DNAm may also have a heritable genetic component as some methylation quantitative trait loci (mQTLs) located in the vicinity of smoking related CpG sites have been shown to alter methylation patterns (Gao et al., 2017). Identifying whether smoking is a necessary and sufficient condition to trigger/ affect changes in DNAm is important because these molecular signatures may serve as clinical biomarkers of lifetime smoking exposure and could also shed light on mechanisms by which tobacco exposure leads to diseases. To estimate the causal effect of own-cigarette smoking on epigenomic signatures, this study will exploit state- and cohort-level variation in cigarette taxation using DNAm pilot data from the Health and Retirement Study (HRS) (N~4,000).