Considering what was seen with AUD and quantity/frequency measures of alcohol use, it would seem important to evaluate the analogous dependence trait for smoking behaviours. Several definitions of nicotine dependence are in common use, based on the Fagerström Test for Nicotine Dependence (FTND)24 or on DSM-IV or DSM-5 (Box 1). In addition to the CHRNA3–CHRNA5–CHRNB4 locus, DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) was identified as associated with nicotine dependence (FTND) in a meta-analysis study that included 38,602 smokers25, with both EUR and AAs contributing to the finding. Several studies have reported significant association with related phenotypes, including “time to first cigarette” e.g. REF26. An FTND GWAS including 58,000 smokers observed an 8.6% SNP-based heritability and identified five GWS loci (e.g., teneurin transmembrane protein 2 (TENM2) and dopamine beta-hydroxylase (DBH)) that were enriched for transcriptomic regulatory mechanisms in the cerebellum27.
