GWAS of nicotine dependence phenotypes have generally been smaller. Some GWAS of nicotine dependence-related phenotypes have focused on data collected from short questionnaires such as the Fagerström Test for Nicotine Dependence (FTND4). The FTND is a 6-item questionnaire which includes cigarettes smoked per day as an ordinal indicator. The largest GWAS of FTND (defined as 0–3 for mild, 4–6 for moderate, and 7–10 for severe dependence) identified 5 loci4. Given the strong genome-wide genetic correlation between CPD and FTND (rg=0.95)4, these GWAS were combined into a single phenotype, problematic tobacco use (PTU), in another study5 using multi-trait analysis of GWAS (MTAG). A recent GWAS meta-analysis of ICD-TUD from electronic health records (EHR; see Table 1) reached nearly 900,000 samples and identified 88 loci6, all of which had been implicated in prior smoking-related GWAS. ICD-TUD showed modest genetic correlations with cigarettes per day (rg = 0.44)6 and FTND (rg = 0.63).
