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. Furberg; Talin 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

doi:10.1038/ng.571

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 journal › Article › peer-review

757 Scopus citations

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 language	English (US)
Pages (from-to)	441-447
Number of pages	7
Journal	Nature genetics
Volume	42
Issue number	5
DOIs	https://doi.org/10.1038/ng.571
State	Published - May 2010
Externally published	Yes

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.571

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

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

@article{0616d23f3a924954b6f71d2706271939,

title = "Genome-wide meta-analyses identify multiple loci associated with smoking behavior",

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.",

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

note = "Funding Information: This work was funded by the University of North Carolina Lineberger Comprehensive Cancer Center University Cancer Research Fund Award and by US National Cancer Institute K07 CA118412 to H.F. Statistical analyses were carried out on the Genetic Cluster Computer (see URLs), which is supported by the Netherlands Scientific Organization (NWO 480-05-003). Acknowledgments for studies included in TAG are listed in the Supplementary Note.",

year = "2010",

month = may,

doi = "10.1038/ng.571",

language = "English (US)",

volume = "42",

pages = "441--447",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

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.

N1 - Funding Information: This work was funded by the University of North Carolina Lineberger Comprehensive Cancer Center University Cancer Research Fund Award and by US National Cancer Institute K07 CA118412 to H.F. Statistical analyses were carried out on the Genetic Cluster Computer (see URLs), which is supported by the Netherlands Scientific Organization (NWO 480-05-003). Acknowledgments for studies included in TAG are listed in the Supplementary Note.

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.

UR - http://www.scopus.com/inward/record.url?scp=77951711343&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951711343&partnerID=8YFLogxK

U2 - 10.1038/ng.571

DO - 10.1038/ng.571

M3 - Article

C2 - 20418890

AN - SCOPUS:77951711343

SN - 1061-4036

VL - 42

SP - 441

EP - 447

JO - Nature genetics

JF - Nature genetics

IS - 5

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this