DSM-IV criteria were used to define dependent cases for alcohol, cannabis, cocaine, and opioids. For nicotine dependence, we defined the proxy of heavy smoking cases (CPD > 20) and light smoking controls (CPD ≤ 10) for current and former smokers, based on CPD when they were smoking; if multiple measurements were available the maximum value was used. Heavy versus light CPD is more commonly measured than nicotine dependence and has been an informative proxy for nicotine dependence in large meta-analyses (Chen et al. 2012b; Hartz et al. 2012; Saccone et al. 2010); smokers meeting this threshold strongly overlap with nicotine dependent smokers. Because CPD does not account for dependence items such as withdrawal (Lessov et al. 2004), secondary analyses examined the effect of redefining general dependence using standard definitions of nicotine dependence (Fagerström Test for Nicotine Dependence (Heatherton et al. 1991) and DSM-IV), in the subset of studies for which these were available.
