Smoking is a common risk factor for many diseases and a leading cause of mortality [1]. It is well known that smoking persistence, smoking quantity and nicotine dependence are highly heritable traits, and approximately 30–80% of inter-individual variance is attributable to genetic factors [2], [3]. Recently, genome-wide association studies (GWAS) and genome-wide meta-analyses have identified several genetic loci that are associated with smoking quantity (as estimated by the number of cigarettes smoked per day, CPD), smoking initiation, smoking cessation and age of smoking initiation [4]–[6]. However, these studies were conducted in subjects of European descent, and few GWAS have been performed in any Asian population, even though this group accounts for two-thirds of the world population. Thus, studies in Asian populations might provide novel insight into the genetic architecture of smoking behavior and smoking-related diseases. Here, we report a large-scale GWAS and a replication study examining CPD in 17,158 Japanese subjects. We assessed genome-wide single-nucleotide polymorphisms (SNPs) along with common copy number polymorphisms (CNPs) and identified haplotypes with a SNP and a CNP at the CYP2A6 locus that is a
