The percentage of variance explained by our novel independent SNPs was very high (up to 31%), exceeding the estimates for the four functional variants frequently genotyped in Caucasians [16]. Our novel variants likely tag multiple functional variants, both known and unidentified ones, and thus capture information on relevant haplotypes. The population-attributable effect of the novel independent variants thus is far greater than that of the known functional variants, and for the purpose of estimating the rate of nicotine metabolism our novel SNPs are more informative than the known previously characterized reduced-activity variants.
