The Tobacco and Genetics Consortium (TAG) conducted meta-analyses of smoking phenotypes within 16 cohorts (n = 74,053) and partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions. The study identified three loci associated with the number of cigarettes smoked per day (CPD): a synonymous SNP in *CHRNA3* (rs1051730[A], β = 1.03, *P* = 2.8 × 10^−73^), two SNPs in *EGLN2* (rs1329650[G], β = 0.367, *P* = 5.7 × 10^−10^; rs1028936[A], β = 0.446, *P* = 1.3 × 10^−9^), and one SNP in *BDNF* (rs6265[C], OR = 1.06, *P* = 1.8 × 10^−8^) associated with smoking initiation. One SNP near *DBH* (rs3025343[C], OR = 1.12, *P* = 3.6 × 10^−8^) was significantly associated with smoking cessation. These findings suggest that separate genetic loci contribute modestly to phenotypic variability in each aspect of smoking behavior, which may have implications for the design and targeting of smoking cessation therapies and tobacco control efforts.The Tobacco and Genetics Consortium (TAG) conducted meta-analyses of smoking phenotypes within 16 cohorts (n = 74,053) and partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions. The study identified three loci associated with the number of cigarettes smoked per day (CPD): a synonymous SNP in *CHRNA3* (rs1051730[A], β = 1.03, *P* = 2.8 × 10^−73^), two SNPs in *EGLN2* (rs1329650[G], β = 0.367, *P* = 5.7 × 10^−10^; rs1028936[A], β = 0.446, *P* = 1.3 × 10^−9^), and one SNP in *BDNF* (rs6265[C], OR = 1.06, *P* = 1.8 × 10^−8^) associated with smoking initiation. One SNP near *DBH* (rs3025343[C], OR = 1.12, *P* = 3.6 × 10^−8^) was significantly associated with smoking cessation. These findings suggest that separate genetic loci contribute modestly to phenotypic variability in each aspect of smoking behavior, which may have implications for the design and targeting of smoking cessation therapies and tobacco control efforts.