Another important aspect of this study is that the tag-SNP (rs11878604) is located in an intergenic region, which resulted in the collapse of the functional effect of multiple deleterious SNPs (two nonsense SNPs in exon 9 and a SNP in TATA box of CYP2A6) that had the most significant associations with CPD after conditioning on the CNP (rs8102683). In these cases, we would generally employ a fine-mapping approach to investigate the region using imputation with data from the 1000 Genomes project or deep resequencing of nearby genes. However, if the tag-SNP was associated with a number of rare variants in a gene or a gene cluster, the single SNP test after imputation or resequencing may not be able to fully explain the underlying phenomena because the common tag-SNP will still be the most powerful marker in the region. Therefore, we may have to take into account the effect of multiple deleterious SNPs for regions in which haplotype analysis and collapsing methods [19]–[22] play an important role.
