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

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 (US)
Pages (from-to)441-447
Number of pages7
JournalNature Genetics
Volume42
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

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Single Nucleotide Polymorphism
Meta-Analysis
Smoking
Genome
Tobacco Products
Odds Ratio
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 11
Molecular Epidemiology
Brain-Derived Neurotrophic Factor
Nicotinic Receptors
Smoking Cessation
Tobacco
Confidence Intervals
Phenotype
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Furberg, H., Kim, Y., Dackor, J., Boerwinkle, E., Franceschini, N., Ardissino, D., ... 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

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

In: Nature Genetics, Vol. 42, No. 5, 05.2010, p. 441-447.

Research output: Contribution to journalArticle

Furberg, H, Kim, Y, Dackor, J, Boerwinkle, E, Franceschini, N, Ardissino, D, Bernardinelli, L, Mannucci, PM, Mauri, F, Merlini, PA, Absher, D, Assimes, TL, Fortmann, SP, Iribarren, C, Knowles, JW, Quertermous, T, Ferrucci, L, Tanaka, T, Bis, JC, Furberg, CD, Haritunians, T, McKnight, B, Psaty, BM, Taylor, KD, Thacker, EL, Almgren, P, Groop, L, Ladenvall, C, Boehnke, M, Jackson, AU, Mohlke, KL, Stringham, HM, Tuomilehto, J, Benjamin, EJ, Hwang, SJ, Levy, D, Preis, SR, Vasan, RS, Duan, J, Gejman, PV, Levinson, DF, Sanders, AR, Shi, J, Lips, EH, McKay, JD, Agudo, A, Barzan, L, Bencko, V, Benhamou, S, Castellsagué, X, Canova, C, Conway, DI, Fabianova, E, Foretova, L, Janout, V, Healy, CM, Holcátová, I, Kjaerheim, K, Lagiou, P, Lissowska, J, Lowry, R, MacFarlane, TV, Mates, D, Richiardi, L, Rudnai, P, Szeszenia-Dabrowska, N, Zaridze, D, Znaor, A, Lathrop, M, Brennan, P, Bandinelli, S, Frayling, TM, Guralnik, JM, Milaneschi, Y, Perry, JRB, Altshuler, D, Elosua, R, Kathiresan, S, Lucas, G, Melander, O, O'Donnell, CJ, Salomaa, V, Schwartz, SM, Voight, BF, Penninx, BW, Smit, JH, Vogelzangs, N, Boomsma, DI, De Geus, EJC, Vink, JM, Willemsen, G, Chanock, SJ, Gu, F, Hankinson, SE, Hunter, DJ, Hofman, A, Tiemeier, H, Uitterlinden, AG, Van Duijn, CM, Walter, S, Chasman, DI, Everett, BM, Paré, G, Ridker, PM, Li, MD, Maes, HH, Audrain-Mcgovern, J, Posthuma, D, Thornton, LM, Lerman, C, Kaprio, J, Rose, JE, Ioannidis, JPA, Kraft, P, Lin, DY & Sullivan, PF 2010, 'Genome-wide meta-analyses identify multiple loci associated with smoking behavior', Nature Genetics, vol. 42, no. 5, pp. 441-447. https://doi.org/10.1038/ng.571
Furberg H, Kim Y, Dackor J, Boerwinkle E, Franceschini N, Ardissino D et al. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature Genetics. 2010 May;42(5):441-447. https://doi.org/10.1038/ng.571
Furberg, Helena ; Kim, Yunjung ; Dackor, Jennifer ; Boerwinkle, Eric ; Franceschini, Nora ; Ardissino, Diego ; Bernardinelli, Luisa ; Mannucci, Pier M. ; Mauri, Francesco ; Merlini, Piera A. ; Absher, Devin ; Assimes, Themistocles L. ; Fortmann, Stephen P. ; Iribarren, Carlos ; Knowles, Joshua W. ; Quertermous, Thomas ; Ferrucci, Luigi ; Tanaka, Toshiko ; Bis, Joshua C. ; Furberg, Curt D. ; Haritunians, Talin ; McKnight, Barbara ; Psaty, Bruce M. ; Taylor, Kent D. ; Thacker, Evan L. ; Almgren, Peter ; Groop, Leif ; Ladenvall, Claes ; Boehnke, Michael ; Jackson, Anne U. ; Mohlke, Karen L. ; Stringham, Heather M. ; Tuomilehto, Jaakko ; Benjamin, Emelia J. ; Hwang, Shih Jen ; Levy, Daniel ; Preis, Sarah Rosner ; Vasan, Ramachandran S. ; Duan, Jubao ; Gejman, Pablo V. ; Levinson, Douglas F. ; Sanders, Alan R. ; Shi, Jianxin ; Lips, Esther H. ; McKay, James D. ; Agudo, Antonio ; Barzan, Luigi ; Bencko, Vladimir ; Benhamou, Simone ; Castellsagué, Xavier ; Canova, Cristina ; Conway, David I. ; Fabianova, Eleonora ; Foretova, Lenka ; Janout, Vladimir ; Healy, Claire M. ; Holcátová, Ivana ; Kjaerheim, Kristina ; Lagiou, Pagona ; Lissowska, Jolanta ; Lowry, Ray ; MacFarlane, Tatiana V. ; Mates, Dana ; Richiardi, Lorenzo ; Rudnai, Peter ; Szeszenia-Dabrowska, Neonilia ; Zaridze, David ; Znaor, Ariana ; Lathrop, Mark ; Brennan, Paul ; Bandinelli, Stefania ; Frayling, Timothy M. ; Guralnik, Jack M. ; Milaneschi, Yuri ; Perry, John R B ; Altshuler, David ; Elosua, Roberto ; Kathiresan, Sek ; Lucas, Gavin ; Melander, Olle ; O'Donnell, Christopher J. ; Salomaa, Veikko ; Schwartz, Stephen M. ; Voight, Benjamin F. ; Penninx, Brenda W. ; Smit, Johannes H. ; Vogelzangs, Nicole ; Boomsma, Dorret I. ; De Geus, Eco J C ; Vink, Jacqueline M. ; Willemsen, Gonneke ; Chanock, Stephen J. ; Gu, Fangyi ; Hankinson, Susan E. ; Hunter, David J. ; Hofman, Albert ; Tiemeier, Henning ; Uitterlinden, Andre G. ; Van Duijn, Cornelia M. ; Walter, Stefan ; Chasman, Daniel I. ; Everett, Brendan M. ; Paré, Guillaume ; Ridker, Paul M. ; Li, Ming D. ; Maes, Hermine H. ; Audrain-Mcgovern, Janet ; Posthuma, Danielle ; Thornton, Laura M. ; Lerman, Caryn ; Kaprio, Jaakko ; Rose, Jed E. ; Ioannidis, John P A ; Kraft, Peter ; Lin, Dan Yu ; Sullivan, Patrick F. / Genome-wide meta-analyses identify multiple loci associated with smoking behavior. In: Nature Genetics. 2010 ; Vol. 42, No. 5. pp. 441-447.
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T1 - Genome-wide meta-analyses identify multiple loci associated with smoking behavior

AU - Furberg, Helena

AU - Kim, Yunjung

AU - Dackor, Jennifer

AU - Boerwinkle, Eric

AU - Franceschini, Nora

AU - Ardissino, Diego

AU - Bernardinelli, Luisa

AU - Mannucci, Pier M.

AU - Mauri, Francesco

AU - Merlini, Piera A.

AU - Absher, Devin

AU - Assimes, Themistocles L.

AU - Fortmann, Stephen P.

AU - Iribarren, Carlos

AU - Knowles, Joshua W.

AU - Quertermous, Thomas

AU - Ferrucci, Luigi

AU - Tanaka, Toshiko

AU - Bis, Joshua C.

AU - Furberg, Curt D.

AU - Haritunians, Talin

AU - McKnight, Barbara

AU - Psaty, Bruce M.

AU - Taylor, Kent D.

AU - Thacker, Evan L.

AU - Almgren, Peter

AU - Groop, Leif

AU - Ladenvall, Claes

AU - Boehnke, Michael

AU - Jackson, Anne U.

AU - Mohlke, Karen L.

AU - Stringham, Heather M.

AU - Tuomilehto, Jaakko

AU - Benjamin, Emelia J.

AU - Hwang, Shih Jen

AU - Levy, Daniel

AU - Preis, Sarah Rosner

AU - Vasan, Ramachandran S.

AU - Duan, Jubao

AU - Gejman, Pablo V.

AU - Levinson, Douglas F.

AU - Sanders, Alan R.

AU - Shi, Jianxin

AU - Lips, Esther H.

AU - McKay, James D.

AU - Agudo, Antonio

AU - Barzan, Luigi

AU - Bencko, Vladimir

AU - Benhamou, Simone

AU - Castellsagué, Xavier

AU - Canova, Cristina

AU - Conway, David I.

AU - Fabianova, Eleonora

AU - Foretova, Lenka

AU - Janout, Vladimir

AU - Healy, Claire M.

AU - Holcátová, Ivana

AU - Kjaerheim, Kristina

AU - Lagiou, Pagona

AU - Lissowska, Jolanta

AU - Lowry, Ray

AU - MacFarlane, Tatiana V.

AU - Mates, Dana

AU - Richiardi, Lorenzo

AU - Rudnai, Peter

AU - Szeszenia-Dabrowska, Neonilia

AU - Zaridze, David

AU - Znaor, Ariana

AU - Lathrop, Mark

AU - Brennan, Paul

AU - Bandinelli, Stefania

AU - Frayling, Timothy M.

AU - Guralnik, Jack M.

AU - Milaneschi, Yuri

AU - Perry, John R B

AU - Altshuler, David

AU - Elosua, Roberto

AU - Kathiresan, Sek

AU - Lucas, Gavin

AU - Melander, Olle

AU - O'Donnell, Christopher J.

AU - Salomaa, Veikko

AU - Schwartz, Stephen M.

AU - Voight, Benjamin F.

AU - Penninx, Brenda W.

AU - Smit, Johannes H.

AU - Vogelzangs, Nicole

AU - Boomsma, Dorret I.

AU - De Geus, Eco J C

AU - Vink, Jacqueline M.

AU - Willemsen, Gonneke

AU - Chanock, Stephen J.

AU - Gu, Fangyi

AU - Hankinson, Susan E.

AU - Hunter, David J.

AU - Hofman, Albert

AU - Tiemeier, Henning

AU - Uitterlinden, Andre G.

AU - Van Duijn, Cornelia M.

AU - Walter, Stefan

AU - Chasman, Daniel I.

AU - Everett, Brendan M.

AU - Paré, Guillaume

AU - Ridker, Paul M.

AU - Li, Ming D.

AU - Maes, Hermine H.

AU - Audrain-Mcgovern, Janet

AU - Posthuma, Danielle

AU - Thornton, Laura M.

AU - Lerman, Caryn

AU - Kaprio, Jaakko

AU - Rose, Jed E.

AU - Ioannidis, John P A

AU - Kraft, Peter

AU - Lin, Dan Yu

AU - Sullivan, Patrick F.

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

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