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

Helena Furberg, Yunjung Kim, Jennifer Dackor, Eric Boerwinkle, Nora Franceschini, Diego Ardissino, Luisa Bernardinelli, Pier M. Mannucci, Francesco Mauri, Piera A. Merlini, Devin Absher, Themistocles L. Assimes, Stephen P. Fortmann, Carlos Iribarren, Joshua W. Knowles, Thomas Quertermous, Luigi Ferrucci, Toshiko Tanaka, Joshua C. Bis, Curt D. FurbergTalin Haritunians, Barbara McKnight, Bruce M. Psaty, Kent D. Taylor, Evan L. Thacker, Peter Almgren, Leif Groop, Claes Ladenvall, Michael Boehnke, Anne U. Jackson, Karen L. Mohlke, Heather M. Stringham, Jaakko Tuomilehto, Emelia J. Benjamin, Shih Jen Hwang, Daniel Levy, Sarah Rosner Preis, Ramachandran S. Vasan, Jubao Duan, Pablo V. Gejman, Douglas F. Levinson, Alan R. Sanders, Jianxin Shi, Esther H. Lips, James D. McKay, Antonio Agudo, Luigi Barzan, Vladimir Bencko, Simone Benhamou, Xavier Castellsagué, Cristina Canova, David I. Conway, Eleonora Fabianova, Lenka Foretova, Vladimir Janout, Claire M. Healy, Ivana Holcátová, Kristina Kjaerheim, Pagona Lagiou, Jolanta Lissowska, Ray Lowry, Tatiana V. MacFarlane, Dana Mates, Lorenzo Richiardi, Peter Rudnai, Neonilia Szeszenia-Dabrowska, David Zaridze, Ariana Znaor, Mark Lathrop, Paul Brennan, Stefania Bandinelli, Timothy M. Frayling, Jack M. Guralnik, Yuri Milaneschi, John R.B. Perry, David Altshuler, Roberto Elosua, Sek Kathiresan, Gavin Lucas, Olle Melander, Christopher J. O'Donnell, Veikko Salomaa, Stephen M. Schwartz, Benjamin F. Voight, Brenda W. Penninx, Johannes H. Smit, Nicole Vogelzangs, Dorret I. Boomsma, Eco J.C. De Geus, Jacqueline M. Vink, Gonneke Willemsen, Stephen J. Chanock, Fangyi Gu, Susan E. Hankinson, David J. Hunter, Albert Hofman, Henning Tiemeier, Andre G. Uitterlinden, Cornelia M. Van Duijn, Stefan Walter, Daniel I. Chasman, Brendan M. Everett, Guillaume Paré, Paul M. Ridker, Ming D. Li, Hermine H. Maes, Janet Audrain-Mcgovern, Danielle Posthuma, Laura M. Thornton, Caryn Lerman, Jaakko Kaprio, Jed E. Rose, John P.A. Ioannidis, Peter Kraft, Dan Yu Lin, Patrick F. Sullivan

Research output: Contribution to journalArticle

702 Citations (Scopus)

Abstract

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 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 × 10 8). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 × 10 8) was significantly associated with smoking cessation.

Original languageEnglish
Pages (from-to)441-447
Number of pages7
JournalNature genetics
Volume42
Issue number5
DOIs
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Genome-wide meta-analyses identify multiple loci associated with smoking behavior'. Together they form a unique fingerprint.

  • Cite this

    Furberg, H., Kim, Y., Dackor, J., Boerwinkle, E., Franceschini, N., Ardissino, D., Bernardinelli, L., Mannucci, P. M., Mauri, F., Merlini, P. A., Absher, D., Assimes, T. L., Fortmann, S. P., Iribarren, C., Knowles, J. W., Quertermous, T., Ferrucci, L., Tanaka, T., Bis, J. C., ... Sullivan, P. F. (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature genetics, 42(5), 441-447. https://doi.org/10.1038/ng.571