GWASs of nicotine dependence phenotypes have generally been smaller. Some GWASs of nicotine dependence-related phenotypes have focused on data collected from short questionnaires, such as the FTND (Quach et al., 2020). The FTND is a six-item questionnaire that 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 five loci (Quach et al., 2020). Given the strong genome-wide genetic correlation between CPD and FTND (r g = 0.95) (Quach et al., 2020), these GWASs were combined into a single phenotype, PTU, in another study (Hatoum et al., 2022) using multi-trait analysis of GWAS. A recent GWAS meta-analysis of ICD-TUD from electronic health records (see Table 1) reached nearly 900,000 samples and identified 88 loci (Toikumo et al., 2024), all of which had been implicated in prior smoking-related GWASs. ICD-TUD showed moderate genetic correlations with CPD (r g = 0.44) (Toikumo et al., 2024) and FTND (r g = 0.63).
