We included individuals from eight cohorts across five different sites (Figure 1a for an overview of the cohorts; Supplementary Table 2 for sample sizes). The methods to ascertain cases were identical for seven of these cohorts. Individuals were identified as cases if they met criteria for a TUD phecode (a TUD ICD9 or ICD10 code on two or more separate visits, described in Supplementary Table 3); controls were screened for the absence of a TUD diagnostic code. We benchmarked the TUD-EHR definition against self-reported smoking questionnaire data and other comorbid ICD codes (Supplementary Table 4). Across contributing biobanks, cases were enriched for ever smokers (92–99%), with only a minor proportion (<2%) of cases self-identifying as never-smokers (Supplementary Table 5). In contrast, a smaller proportion of controls were ever smokers (17–56%), with a larger proportion self-identifying as never-smokers (39–73%). Attempts at smoking cessation were reported by 15–25% of controls and 65–95% of cases. Controls were comparable to cases on age and sex but reported much lower prevalences of other substance and psychiatric disorders than cases. Thus, almost all TUD cases have evidence of being either former or current smokers based on available self-report data.
