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

H Furberg; Y. Kim; J Dackor; E Boerwinkle; N Franceschini; D Ardissino; L Bernardinelli; PM 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; JX 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 Holcatova; 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; JRB 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; EJC de Geus; JM Vink; G Willemsen; SJ Chanock; FY Gu; SE Hankinson; DJ Hunter; Bert Hofman; Henning Tiemeier; André Uitterlinden; Cornelia Duijn; Stefan Walter; DI Chasman; BM Everett; G Pare; PM Ridker; MD Li; HH Maes; J Audrain-McGovern; D Posthuma; LM Thornton; C Lerman; J Kaprio; JE Rose; JPA Ioannidis; P Kraft; DY Lin; PF Sullivan

doi:10.1038/ng.571

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

H Furberg
, Y. Kim
, J Dackor
, E Boerwinkle
, N Franceschini
, D Ardissino
, L Bernardinelli
, PM 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, JX 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 Holcatova, 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, JRB 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, EJC de Geus, JM Vink, G Willemsen, SJ Chanock, FY Gu, SE Hankinson, DJ Hunter, Bert Hofman, Henning Tiemeier, André Uitterlinden, Cornelia Duijn, Stefan Walter, DI Chasman, BM Everett, G Pare, PM Ridker, MD Li, HH Maes, J Audrain-McGovern, D Posthuma, LM Thornton, C Lerman, J Kaprio, JE Rose, JPA Ioannidis, P Kraft, DY Lin, PF Sullivan

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Research output: Contribution to journal › Article › Academic › peer-review

907 Citations (Scopus)

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.

Original language	Undefined/Unknown
Pages (from-to)	441-U134
Journal	Nature Genetics
Volume	42
Issue number	5
DOIs	https://doi.org/10.1038/ng.571
Publication status	Published - 2010

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EMC NIHES-04-55-01

Access to Document

10.1038/ng.571

http://hdl.handle.net/1765/28349

Cite this

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., ... Sullivan, PF. (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature Genetics, 42(5), 441-U134. https://doi.org/10.1038/ng.571

@article{d2c447d8db24424d8becd4e18a7f3f4b,

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

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

year = "2010",

doi = "10.1038/ng.571",

language = "Undefined/Unknown",

volume = "42",

pages = "441--U134",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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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, JX, Lips, EH, Mckay, JD, Agudo, A, Barzan, L, Bencko, V, Benhamou, S, Castellsague, X, Canova, C, Conway, DI, Fabianova, E, Foretova, L, Janout, V, Healy, CM, Holcatova, 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, FY, Hankinson, SE, Hunter, DJ, Hofman, B , Tiemeier, H, Uitterlinden, A, Duijn, C, Walter, S, Chasman, DI, Everett, BM, Pare, 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-U134. https://doi.org/10.1038/ng.571

TY - JOUR

T1 - Genome-wide meta-analyses identify multiple loci associated with smoking behavior

AU - Furberg, H

AU - Kim, Y.

AU - Dackor, J

AU - Boerwinkle, E

AU - Franceschini, N

AU - Ardissino, D

AU - Bernardinelli, L

AU - Mannucci, PM

AU - Mauri, F

AU - Merlini, PA

AU - Absher, D

AU - Assimes, TL

AU - Fortmann, SP

AU - Iribarren, C

AU - Knowles, JW

AU - Quertermous, T

AU - Ferrucci, L

AU - Tanaka, T

AU - Bis, JC

AU - Furberg, CD

AU - Haritunians, T

AU - McKnight, B

AU - Psaty, BM

AU - Taylor, KD

AU - Thacker, EL

AU - Almgren, P

AU - Groop, L

AU - Ladenvall, C

AU - Boehnke, M

AU - Jackson, AU

AU - Mohlke, KL

AU - Stringham, HM

AU - Tuomilehto, J

AU - Benjamin, EJ

AU - Hwang, SJ

AU - Levy, D

AU - Preis, SR

AU - Vasan, RS

AU - Duan, J

AU - Gejman, PV

AU - Levinson, DF

AU - Sanders, AR

AU - Shi, JX

AU - Lips, EH

AU - Mckay, JD

AU - Agudo, A

AU - Barzan, L

AU - Bencko, V

AU - Benhamou, S

AU - Castellsague, X

AU - Canova, C

AU - Conway, DI

AU - Fabianova, E

AU - Foretova, L

AU - Janout, V

AU - Healy, CM

AU - Holcatova, I

AU - Kjaerheim, K

AU - Lagiou, P

AU - Lissowska, J

AU - Lowry, R

AU - Macfarlane, TV

AU - Mates, D

AU - Richiardi, L

AU - Rudnai, P

AU - Szeszenia-Dabrowska, N

AU - Zaridze, D

AU - Znaor, A

AU - Lathrop, M

AU - Brennan, P

AU - Bandinelli, S

AU - Frayling, TM

AU - Guralnik, JM

AU - Milaneschi, Y

AU - Perry, JRB

AU - Altshuler, D

AU - Elosua, R

AU - Kathiresan, S

AU - Lucas, G

AU - Melander, O

AU - O'Donnell, CJ

AU - Salomaa, V

AU - Schwartz, SM

AU - Voight, BF

AU - Penninx, BW

AU - Smit, JH

AU - Vogelzangs, N

AU - Boomsma, DI

AU - de Geus, EJC

AU - Vink, JM

AU - Willemsen, G

AU - Chanock, SJ

AU - Gu, FY

AU - Hankinson, SE

AU - Hunter, DJ

AU - Hofman, Bert

AU - Tiemeier, Henning

AU - Uitterlinden, André

AU - Duijn, Cornelia

AU - Walter, Stefan

AU - Chasman, DI

AU - Everett, BM

AU - Pare, G

AU - Ridker, PM

AU - Li, MD

AU - Maes, HH

AU - Audrain-McGovern, J

AU - Posthuma, D

AU - Thornton, LM

AU - Lerman, C

AU - Kaprio, J

AU - Rose, JE

AU - Ioannidis, JPA

AU - Kraft, P

AU - Lin, DY

AU - Sullivan, PF

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1038/ng.571

DO - 10.1038/ng.571

M3 - Article

C2 - 20418890

SN - 1061-4036

VL - 42

SP - 441-U134

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -