On the basis of the combined Phase 1 and Phase 2 GWA data the 15q25.1 association is defined by a 248kb region of strong LD on chromosome 15 extending from 76,499,754bp to 76,747,584bp (Figure 2a). Maximal evidence of a relationship was provided by the SNP rs12914385, which maps at 76,685,778bp (OR = 1.29, 95% CI: 1.21–1.37; P = 3.19 × 10−16; Supplementary Table 1). rs938682 and rs8042374 also provide strong evidence for an association between 15q25 and lung cancer risk (Supplementary Table 2). The relative position of these 3 SNPs to the CHRNA3, CHRNA5, CHRNB4, IREB2, PSMA4, and LOC123688 transcripts, which map to the 248kb region of LD within 15q25.1, is shown in Figure 2a. All three SNPs localise to intron 4 of CHRNA3 strongly favouring variation within this gene as being the basis of 15q25 lung cancer association. rs12914385 and rs938682 / rs8042374 appear to tag different blocks of LD (respective r2 values for: rs938682- rs12914385, rs938682- rs8042374 rs12914385-rs8042374 are 0.22, 1.00 and 0.22 based on HapMap CEU, and 0.18, 0.99, and 0.17 based on UK-GWA Phase 2 controls).
