rs2072661, in the 3′ untranslated region of CHRNB2 at chr1q21.3, has been associated with: abstinence in a RCT randomizing participants to BUP or PLA; initial response to tobacco in adolescent samples; short-term abstinence in a cross-over smoking cessation trial of NRT and PLA; baseline Fagerström Test for Nicotine Dependence score among treatment-seeking smokers; and nausea among treatment-seeking smokers randomized to behavioral therapies and prescribed varenicline (VAR) [35,43,46,53,54]. Candidate gene, genome wide association studies, and meta-analytic studies with a nicotine dependence phenotype have identified three different loci represented by SNPs rs1051730, rs578776 and rs588765 at chr15q25.1 in CHRNA5 and CHRNA3 [30]. rs1051730 and correlated SNPs have been associated with nicotine dependence and lung cancer [18,19,20,22,55], abstinence [23,50], and smoking likelihood during pregnancy [48]. rs578776 and correlated SNPs have been associated with nicotine dependence [18,22,27,30] and abstinence [49]. rs588765 and correlated SNPs have been associated with nicotine dependence [27,30] and with abstinence [51]. Recent research using a single RCT has demonstrated that individuals with chr15q25.1 risk haplotypes [22,23] exhibit statistically significantly reduced abstinence when randomized to PLA versus no effect on abstinence
