This meta-analysis therefore highlights locus 1, locus 2, and locus 3, and indicates dependencies in their effects on risk for heavy smoking. Haplotypes based on these three loci have been described [7], [22] and are seen in HapMap CEU, where the observed haplotype patterns for rs16969968 (locus 1), rs578776 (locus 2), and rs588765 (locus 3) are: A-G-C (frequency 0.425), G-G-T (0.333), G-A-C (0.207), G-A-T (0.035). Only four of the eight possible haplotypes are observed. This is consistent with the correlation structure between the loci. Locus 2 and locus 3 have low correlation with each other (e.g. r2 = 0.07 between rs578776 and rs588765 in HapMap CEU release 23); however their correlation sharply increases when locus 1 is taken into account (e.g. in GG homozygotes at rs16969968, r2 = 0.74 in HapMap CEU).
