Our GWAS identified a significant association on 19q13 that satisfied the genome-wide significance threshold of (Figure 1 and Table S2). This region encompasses a series of CYP2 family genes (Figure S4) and one of the most significantly associated markers was a CNP (rs8102683; ; Table S2), which is located 10 kb upstream of the CYP2A6 gene. Four additional CNPs were also clustered at this locus, and these five CNPs were in strong linkage disequilibrium (LD) with each other (Figure S5). Moreover, haplotype estimation revealed that the five CNPs shared a common deletion (frequency ; Table S3). These findings suggest that the five CNPs are located within the same copy number variation region. In fact, the depth of coverage for the 89 Japanese subjects from the 1000 Genomes Project (Phase I 2011-11-23; see URLs) clearly showed the common deletion region ranging from the 3′ end of the CYP2A6 gene to the 3′ end of the CYP2A7 gene (Figure S6), which is a region that encompasses all five CNP markers. Since the CYP2A6 gene encodes a nicotine-metabolizing enzyme [12], [13], it is
