The earliest GWAS in the addiction field was conducted for nicotine dependence [6, 7], implicating nicotinic acetylcholine receptor genes on chromosomes 15q25 (CHRNA5-CHRNA3-CHRNB4) and 8p11 (CHRNB3-CHRNA6), which have since been firmly established in other studies of nicotine dependence and related smoking phenotypes (Table 1). To date, at least 26 GWAS analyses (largest N=74,035 [8]) have been conducted for self-reported phenotypes [6, 9–11, 8, 12–27], including ever vs. never smoking, former vs. current smoking, cigarettes per day (CPD), nicotine dependence defined by Fagerström Test for Nicotine Dependence (FTND) or Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) [6, 9–11, 8, 12–27], nicotine withdrawal defined by DSM-IV, as well as smoking biomarkers [28–32]. The FTND, a validated, expert-recommended, low-burden questionnaire of six items used to assess severity of physiological nicotine dependence symptoms among cigarette smokers [33], is the most widely used measure of nicotine dependence.
