Tobacco smoking kills almost 6 million people each year (World Health Organization, 2015) 1. Despite smoking prevalence decreasing in the past 30 years, there has been a steady increase in the absolute number of smokers, i.e., from 721 million in 1980 to 967 million in 2012 due to accelerated population growth 2. Aside from environmental influences such as e.g., tobacco availability and social pressure 3, genetic factors are implicated in all stages of smoking 4, from experimentation 5 to dependence 5, 6 and cessation 7. Although genome-wide association studies (GWASs; see 8-10 for a recent overview) and the meta-analyses conducted by large consortia 11-13 have provided important insights into the biological bases of smoking, progress has been slow due to the small effects of the single nucleotide polymorphisms (SNPs) and to the multiple testing burden. In genetic studies, the power to detect small effects is linked primarily to sample size (given a fixed alpha level). However, power may also depend on the nature of the genotype-phenotype relation 14, 15. Most consortia focus initially on individual SNPs showing the strongest evidence
