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

Furberg, Helena; Kim, YunJung; Dackor, Jennifer; Boerwinkle, Eric; Franceschini, Nora; Ardissino, Diego; Bernardinelli, Luisa; Mannucci, Pier M.; Mauri, Francesco and Merlini, Piera A., et al. (2010) In Nature Genetics 42(5). p.134-441
Abstract
Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. 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], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and... (More)
Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. 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], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 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. (Less)
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Nature Genetics
volume
42
issue
5
pages
134 - 441
publisher
Nature Publishing Group
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  • wos:000277179500017
  • scopus:77951711343
ISSN
1546-1718
DOI
10.1038/ng.571
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English
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e24186cf-b864-4612-9009-34dafc946a18 (old id 1619189)
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2010-06-22 09:18:31
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@article{e24186cf-b864-4612-9009-34dafc946a18,
  abstract     = {Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. 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], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 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.},
  author       = {Furberg, Helena and Kim, YunJung and Dackor, Jennifer and Boerwinkle, Eric and Franceschini, Nora and Ardissino, Diego and Bernardinelli, Luisa and Mannucci, Pier M. and Mauri, Francesco and Merlini, Piera A. and Absher, Devin and Assimes, Themistocles L. and Fortmann, Stephen P. and Iribarren, Carlos and Knowles, Joshua W. and Quertermous, Thomas and Ferrucci, Luigi and Tanaka, Toshiko and Bis, Joshua C. and Furberg, Curt D. and Haritunians, Talin and McKnight, Barbara and Psaty, Bruce M. and Taylor, Kent D. and Thacker, Evan L. and Almgren, Peter and Groop, Leif and Ladenvall, Claes and Boehnke, Michael and Jackson, Anne U. and Mohlke, Karen L. and Stringham, Heather M. and Tuomilehto, Jaakko and Benjamin, Emelia J. and Hwang, Shih-Jen and Levy, Daniel and Preis, Sarah Rosner and Vasan, Ramachandran S. and Duan, Jubao and Gejman, Pablo V. and Levinson, Douglas F. and Sanders, Alan R. and Shi, Jianxin and Lips, Esther H. and Mckay, James D. and Agudo, Antonio and Barzan, Luigi and Bencko, Vladimir and Benhamou, Simone and Castellsague, Xavier and Canova, Cristina and Conway, David I. and Fabianova, Eleonora and Foretova, Lenka and Janout, Vladimir and Healy, Claire M. and Holcatova, Ivana and Kjaerheim, Kristina and Lagiou, Pagona and Lissowska, Jolanta and Lowry, Ray and Macfarlane, Tatiana V. and Mates, Dana and Richiardi, Lorenzo and Rudnai, Peter and Szeszenia-Dabrowska, Neonilia and Zaridze, David and Znaor, Ariana and Lathrop, Mark and Brennan, Paul and Bandinelli, Stefania and Frayling, Timothy M. and Guralnik, Jack M. and Milaneschi, Yuri and Perry, John R. B. and Altshuler, David and Elosua, Roberto and Kathiresan, Sek and Lucas, Gavin and Melander, Olle and O'Donnell, Christopher J. and Salomaa, Veikko and Schwartz, Stephen M. and Voight, Benjamin F. and Penninx, Brenda W. and Smit, Johannes H. and Vogelzangs, Nicole and Boomsma, Dorret I. and de Geus, Eco J. C. and Vink, Jacqueline M. and Willemsen, Gonneke and Chanock, Stephen J. and Gu, Fangyi and Hankinson, Susan E. and Hunter, David J. and Hofman, Albert and Tiemeier, Henning and Uitterlinden, Andre G. and van Duijn, Cornelia M. and Walter, Stefan and Chasman, Daniel I. and Everett, Brendan M. and Pare, Guillaume and Ridker, Paul M. and Li, Ming D. and Maes, Hermine H. and Audrain-McGovern, Janet and Posthuma, Danielle and Thornton, Laura M. and Lerman, Caryn and Kaprio, Jaakko and Rose, Jed E. and Ioannidis, John P. A. and Kraft, Peter and Lin, Dan-Yu and Sullivan, Patrick F.},
  issn         = {1546-1718},
  language     = {eng},
  number       = {5},
  pages        = {134--441},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Genome-wide meta-analyses identify multiple loci associated with smoking behavior},
  url          = {http://dx.doi.org/10.1038/ng.571},
  volume       = {42},
  year         = {2010},
}