Cigarette smoking causes nearly one in five deaths in the United States and is recognized as one of the most dangerous risk factors for numerous cancers and chronic diseases (information from Center for Disease Control and Prevention available at https://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/effects_cig_smoking/). Although the harmful consequences of smoking behaviors are widely recognized, many of the mechanisms of the biochemistry by which it affects human health are still unknown. Indeed, beyond the several smoking-disease correlations currently recognized1, 2, there are likely many additional associations to be revealed, especially as ever-larger datasets containing various kinds of medical data become available to researchers. Genetic investigations, such as phenome-wide association studies (PheWAS, i.e., association analysis of known functional alleles with respect to a large number of phenotypes) of known risk alleles can verify association hypotheses and identify novel medically-relevant associations3, 4. Regarding tobacco smoking, several loci have been identified and confirmed by multiple independent studies. The best replicated so far are risk alleles located in the CHRNA3–CHRNA5–CHRNB4 gene cluster that were associated with smoking behaviors (e.g., cigarettes per day) and smoking-associated diseases (e.g., lung cancer)5–7. Beyond
