We next assessed the implications of the observed stronger association of rs1051730–rs16969968 genotype with cotinine levels, compared with self-reported daily cigarette consumption, for the design of future GWAS. The association of rs1051730–rs16969968 with self-reported daily cigarette consumption and cotinine levels indicated by our results suggests that a GWAS would require a sample size in excess of 7000 to detect an association of the rs1051730–rs16969968 variant with self-reported daily cigarette consumption, but a sample size of only 1800–1900 to detect an association with cotinine levels, assuming an additive model for the genetic association, a minor allele frequency of 0.35, an alpha level of 5 × 10−8, and a required power of at least 80%. In addition, a recall-by-genotype design, where rs1051730–rs16969968 homozygotes are preselected, would require a sample size of only 200 to detect this association with cotinine levels, with an alpha level of 0.05, and a required power of at least 80%.
