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Consistent but indirect evidence has implicated genetic factors in smoking behavior^,. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also 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 (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], β = 1.03, standard error (s.e.) = 0.053, P = 2.8 × 10⁻⁷³). Two 10q25 SNPs (rs1329650[G], β = 0.367, s.e. = 0.059, P = 5.7 × 10⁻¹⁰; and rs1028936[A], β = 0.446, s.e. = 0.074, P = 1.3 × 10⁻⁹) and one 9q13 SNP in EGLN2 (rs3733829[G], β = 0.333, s.e. = 0.058, P = 1.0 × 10⁻⁸) also exceeded genome-wide …