Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

Tobacco and Genetics Consortium; Department of Genetics, University of North Carolina, Chapel Hill, NC 27710, USA.

Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE

Original Publication: New York, NY : Nature Pub. Co., c1992-

Genome-Wide Association Study* ; Polymorphism, Single Nucleotide*; Smoking/*genetics; Age Factors ; Alleles ; Chromosome Mapping ; Female ; Genome ; Genotype ; Humans ; Male ; Molecular Epidemiology/methods ; Odds Ratio ; Phenotype ; Receptors, Nicotinic/genetics

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], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

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K07 CA118412-04 United States CA NCI NIH HHS; R01 DK072193 United States DK NIDDK NIH HHS; R01 DA012844 United States DA NIDA NIH HHS; R01 CA082659 United States CA NCI NIH HHS; K07 CA118412 United States CA NCI NIH HHS

Investigator: H Furberg; Y Kim; J Dackor; E Boerwinkle; N Franceschini; D Ardissino; L Bernardinelli; PL Mannucci; F Mauri; PA Merlini; D Absher; TL Assimes; SP Fortmann; C Iribarren; JW Knowles; T Quertermous; L Ferrucci; T Tanaka; JC Bis; CD Furberg; T Haritunians; B McKnight; BM Psaty; KD Taylor; EL Thacker; P Almgren; L Groop; C Ladenvall; M Boehnke; AU Jackson; KL Mohlke; HM Stringham; J Tuomilehto; EJ Benjamin; SJ Hwang; D Levy; SR Preis; RS Vasan; J Duan; PV Gejman; DF Levinson; AR Sanders; J Shi; EH Lips; JD McKay; A Agudo; L Barzan; V Bencko; S Benhamou; X Castellsague; C Canova; DI Conway; E Fabianova; L Foretova; V Janout; CM Healy; I Holcátová; K Kjaerheim; P Lagiou; J Lissowska; R Lowry; TV Macfarlane; D Mates; L Richiardi; P Rudnai; N Szeszenia-Dabrowska; D Zaridze; A Znaor; M Lathrop; P Brennan; S Bandinelli; TM Frayling; JM Guralnik; Y Milaneschi; JR Perry; D Altshuler; R Elosua; S Kathiresan; G Lucas; O Melander; CJ O'Donnell; V Salomaa; SM Schwartz; BF Voight; BW Penninx; JH Smit; N Vogelzangs; DI Boomsma; EJ de Geus; JM Vink; G Willemsen; SJ Chanock; F Gu; SE Hankinson; DJ Hunter; A Hofman; H Tiemeier; AG Uitterlinden; CM van Duijn; S Walter; DI Chasman; BM Everett; G Paré; PM Ridker; MD Li; HH Maes; J Audrain-McGovern; D Posthuma; LM Thornton; C Lerman; J Kaprio; JE Rose; JP Ioannidis; P Kraft; DY Lin; PF Sullivan

0 (Receptors, Nicotinic)
0 (nicotinic receptor subunit alpha3)

Date Created: 20100427 Date Completed: 20100527 Latest Revision: 20220316

20231215

PMC2914600

10.1038/ng.571

20418890