Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers

S.M. Hartz; S.E. Short; N.L. Saccone; R. Culverhouse; L. Chen; T.H. Schwantes-An; H. Coon; Y. Han; S.H. Stephens; J. Sun; X. Chen; F. Ducci; N. Dueker; N. Franceschini; J. Frank; F. Geller; D. Gubjartsson; N.N. Hansel; C. Jiang; K. Keskitalo-Vuokko; Z. Liu; L.P. Lyytikäinen; M. Michel; R. Rawal; A. Rosenberger; P. Scheet; J.R. Shaffer; A. Teumer; J.R. Thompson; J.M. Vink; N. Vogelzangs; A.S. Wenzlaff; W. Wheeler; X. Xiao; B.Z. Yang; S.H. Aggen; A.J. Balmforth; S.E. Baumeister; T. Beaty; S. Bennett; A.W. Bergen; H.A. Boyd; U. Broms; H. Campbell; N. Chatterjee; J. Chen; Y.C. Cheng; S. Cichon; D. Couper; F. Cucca; D.M. Dick; T. Foroud; H. Furberg; I. Giegling; F. Gu; A.S. Hall; J. Hällfors; S. Han; A. M. Hartmann; C. Hayward; K. Heikkilä; J.K. Hewitt; J.J. Hottenga; M.K. Jensen; P. Jousilahti; M. Kaakinen; S.J. Kittner; B. Konte; T. Korhonen; M.T. Landi; T. Laatikainen; M. Leppert; S.M. Levy; R.A. Mathias; D.W. McNeil; S.E. Medland; G.W. Montgomery; T. Muley; T. Murray; M. Nauck; K. North; M.L. Pergadia; O. Polasek; E.M. Ramos; S. Ripatti; A. Risch; I. Ruczinski; I. Rudan; V. Salomaa; D. Schlessinger; U. Styrkársdóttir; A. Terracciano; M. Uda; G. Willemsen; X. Wu; G.R. Abecasis; K. Barnes; H. Bickeböller; E. Boerwinkle; D.I. Boomsma; N. Caporaso; J. Duan; H.J. Edenberg; C. Francks; P.V. Gejman; J. Gelernter; H.J. Grabe; H. Hops; M.R. Jarvelin; J. Viikari; M. Kähönen; K.S. Kendler; T. Lehtimäki; D.F. Levinson; M.L. Marazita; J. Marchini; M. Melbye; B.D. Mitchell; J.C. Murray; M.M. Nöthen; B.W.J.H. Penninx; O. Raitakari; M. Rietschel; D. Rujescu; N.J. Samani; A.R. Sanders; A.G. Schwartz; S. Shete; J. Shi; M. Spitz; K. Stefansson; G.E. Swan; T.E. Thorgeirsson; H. Völzke; Q. Wei; H.E. Wichmann; C.I. Amos; N. Breslau; D.S. Cannon; M. Ehringer; R.A. Grucza; D. Hatsukami; A.C. Heath; E.O. Johnson; J. Kaprio; P. Madden; N.G. Martin; V.L. Stevens; J.A. Stitzel; R.B. Weiss; P. Kraft; L.J. Bierut

doi:https://doi.org/10.1001/archgenpsychiatry.2012.124

Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers

S.M. Hartz, S.E. Short, N.L. Saccone, R. Culverhouse, L. Chen, T.H. Schwantes-An, H. Coon, Y. Han, S.H. Stephens, J. Sun, X. Chen, F. Ducci, N. Dueker, N. Franceschini, J. Frank, F. Geller, D. Gubjartsson, N.N. Hansel, C. Jiang, K. Keskitalo-VuokkoZ. Liu, L.P. Lyytikäinen, M. Michel, R. Rawal, A. Rosenberger, P. Scheet, J.R. Shaffer, A. Teumer, J.R. Thompson, J.M. Vink, N. Vogelzangs, A.S. Wenzlaff, W. Wheeler, X. Xiao, B.Z. Yang, S.H. Aggen, A.J. Balmforth, S.E. Baumeister, T. Beaty, S. Bennett, A.W. Bergen, H.A. Boyd, U. Broms, H. Campbell, N. Chatterjee, J. Chen, Y.C. Cheng, S. Cichon, D. Couper, F. Cucca, D.M. Dick, T. Foroud, H. Furberg, I. Giegling, F. Gu, A.S. Hall, J. Hällfors, S. Han, A. M. Hartmann, C. Hayward, K. Heikkilä, J.K. Hewitt, J.J. Hottenga, M.K. Jensen, P. Jousilahti, M. Kaakinen, S.J. Kittner, B. Konte, T. Korhonen, M.T. Landi, T. Laatikainen, M. Leppert, S.M. Levy, R.A. Mathias, D.W. McNeil, S.E. Medland, G.W. Montgomery, T. Muley, T. Murray, M. Nauck, K. North, M.L. Pergadia, O. Polasek, E.M. Ramos, S. Ripatti, A. Risch, I. Ruczinski, I. Rudan, V. Salomaa, D. Schlessinger, U. Styrkársdóttir, A. Terracciano, M. Uda, G. Willemsen, X. Wu, G.R. Abecasis, K. Barnes, H. Bickeböller, E. Boerwinkle, D.I. Boomsma, N. Caporaso, J. Duan, H.J. Edenberg, C. Francks, P.V. Gejman, J. Gelernter, H.J. Grabe, H. Hops, M.R. Jarvelin, J. Viikari, M. Kähönen, K.S. Kendler, T. Lehtimäki, D.F. Levinson, M.L. Marazita, J. Marchini, M. Melbye, B.D. Mitchell, J.C. Murray, M.M. Nöthen, B.W.J.H. Penninx, O. Raitakari, M. Rietschel, D. Rujescu, N.J. Samani, A.R. Sanders, A.G. Schwartz, S. Shete, J. Shi, M. Spitz, K. Stefansson, G.E. Swan, T.E. Thorgeirsson, H. Völzke, Q. Wei, H.E. Wichmann, C.I. Amos, N. Breslau, D.S. Cannon, M. Ehringer, R.A. Grucza, D. Hatsukami, A.C. Heath, E.O. Johnson, J. Kaprio, P. Madden, N.G. Martin, V.L. Stevens, J.A. Stitzel, R.B. Weiss, P. Kraft, L.J. Bierut

Psychiatry (VUmc)

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

63 Citations (Scopus)

Abstract

Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources: Primary data. Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DataExtraction: Uniform statistical analysis scripts were runlocally. Startingwith94 050ever-smokersfrom43studies, we extracted the heavy smokers (CPD>20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavyvs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01). Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. ©2012 American Medical Association. All rights reserved.

Original language	English
Pages (from-to)	854-860
Journal	Archives of general psychiatry
Volume	69
Issue number	8
DOIs	https://doi.org/10.1001/archgenpsychiatry.2012.124
Publication status	Published - 2012

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https://doi.org/10.1001/archgenpsychiatry.2012.124

Cite this

Hartz, S. M., Short, S. E., Saccone, N. L., Culverhouse, R., Chen, L., Schwantes-An, T. H., Coon, H., Han, Y., Stephens, S. H., Sun, J., Chen, X., Ducci, F., Dueker, N., Franceschini, N., Frank, J., Geller, F., Gubjartsson, D., Hansel, N. N., Jiang, C., ... Bierut, L. J. (2012). Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers. Archives of general psychiatry, 69(8), 854-860. https://doi.org/10.1001/archgenpsychiatry.2012.124

@article{c63b8c9e52dd4c278a0e2ffde4d51846,

title = "Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers",

abstract = "Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources: Primary data. Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DataExtraction: Uniform statistical analysis scripts were runlocally. Startingwith94 050ever-smokersfrom43studies, we extracted the heavy smokers (CPD>20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavyvs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01). Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. {\textcopyright}2012 American Medical Association. All rights reserved.",

author = "S.M. Hartz and S.E. Short and N.L. Saccone and R. Culverhouse and L. Chen and T.H. Schwantes-An and H. Coon and Y. Han and S.H. Stephens and J. Sun and X. Chen and F. Ducci and N. Dueker and N. Franceschini and J. Frank and F. Geller and D. Gubjartsson and N.N. Hansel and C. Jiang and K. Keskitalo-Vuokko and Z. Liu and L.P. Lyytik{\"a}inen and M. Michel and R. Rawal and A. Rosenberger and P. Scheet and J.R. Shaffer and A. Teumer and J.R. Thompson and J.M. Vink and N. Vogelzangs and A.S. Wenzlaff and W. Wheeler and X. Xiao and B.Z. Yang and S.H. Aggen and A.J. Balmforth and S.E. Baumeister and T. Beaty and S. Bennett and A.W. Bergen and H.A. Boyd and U. Broms and H. Campbell and N. Chatterjee and J. Chen and Y.C. Cheng and S. Cichon and D. Couper and F. Cucca and D.M. Dick and T. Foroud and H. Furberg and I. Giegling and F. Gu and A.S. Hall and J. H{\"a}llfors and S. Han and Hartmann, {A. M.} and C. Hayward and K. Heikkil{\"a} and J.K. Hewitt and J.J. Hottenga and M.K. Jensen and P. Jousilahti and M. Kaakinen and S.J. Kittner and B. Konte and T. Korhonen and M.T. Landi and T. Laatikainen and M. Leppert and S.M. Levy and R.A. Mathias and D.W. McNeil and S.E. Medland and G.W. Montgomery and T. Muley and T. Murray and M. Nauck and K. North and M.L. Pergadia and O. Polasek and E.M. Ramos and S. Ripatti and A. Risch and I. Ruczinski and I. Rudan and V. Salomaa and D. Schlessinger and U. Styrk{\'a}rsd{\'o}ttir and A. Terracciano and M. Uda and G. Willemsen and X. Wu and G.R. Abecasis and K. Barnes and H. Bickeb{\"o}ller and E. Boerwinkle and D.I. Boomsma and N. Caporaso and J. Duan and H.J. Edenberg and C. Francks and P.V. Gejman and J. Gelernter and H.J. Grabe and H. Hops and M.R. Jarvelin and J. Viikari and M. K{\"a}h{\"o}nen and K.S. Kendler and T. Lehtim{\"a}ki and D.F. Levinson and M.L. Marazita and J. Marchini and M. Melbye and B.D. Mitchell and J.C. Murray and M.M. N{\"o}then and B.W.J.H. Penninx and O. Raitakari and M. Rietschel and D. Rujescu and N.J. Samani and A.R. Sanders and A.G. Schwartz and S. Shete and J. Shi and M. Spitz and K. Stefansson and G.E. Swan and T.E. Thorgeirsson and H. V{\"o}lzke and Q. Wei and H.E. Wichmann and C.I. Amos and N. Breslau and D.S. Cannon and M. Ehringer and R.A. Grucza and D. Hatsukami and A.C. Heath and E.O. Johnson and J. Kaprio and P. Madden and N.G. Martin and V.L. Stevens and J.A. Stitzel and R.B. Weiss and P. Kraft and L.J. Bierut",

year = "2012",

doi = "https://doi.org/10.1001/archgenpsychiatry.2012.124",

language = "English",

volume = "69",

pages = "854--860",

journal = "Archives of general psychiatry",

issn = "0003-990X",

publisher = "American Medical Association",

number = "8",

}

Hartz, SM, Short, SE, Saccone, NL, Culverhouse, R, Chen, L, Schwantes-An, TH, Coon, H, Han, Y, Stephens, SH, Sun, J, Chen, X, Ducci, F, Dueker, N, Franceschini, N, Frank, J, Geller, F, Gubjartsson, D, Hansel, NN, Jiang, C, Keskitalo-Vuokko, K, Liu, Z, Lyytikäinen, LP, Michel, M, Rawal, R, Rosenberger, A, Scheet, P, Shaffer, JR, Teumer, A, Thompson, JR, Vink, JM, Vogelzangs, N, Wenzlaff, AS, Wheeler, W, Xiao, X, Yang, BZ, Aggen, SH, Balmforth, AJ, Baumeister, SE, Beaty, T, Bennett, S, Bergen, AW, Boyd, HA, Broms, U, Campbell, H, Chatterjee, N, Chen, J, Cheng, YC, Cichon, S, Couper, D, Cucca, F, Dick, DM, Foroud, T, Furberg, H, Giegling, I, Gu, F, Hall, AS, Hällfors, J, Han, S, Hartmann, AM, Hayward, C, Heikkilä, K, Hewitt, JK, Hottenga, JJ, Jensen, MK, Jousilahti, P, Kaakinen, M, Kittner, SJ, Konte, B, Korhonen, T, Landi, MT, Laatikainen, T, Leppert, M, Levy, SM, Mathias, RA, McNeil, DW, Medland, SE, Montgomery, GW, Muley, T, Murray, T, Nauck, M, North, K, Pergadia, ML, Polasek, O, Ramos, EM, Ripatti, S, Risch, A, Ruczinski, I, Rudan, I, Salomaa, V, Schlessinger, D, Styrkársdóttir, U, Terracciano, A, Uda, M, Willemsen, G, Wu, X, Abecasis, GR, Barnes, K, Bickeböller, H, Boerwinkle, E, Boomsma, DI, Caporaso, N, Duan, J, Edenberg, HJ, Francks, C, Gejman, PV, Gelernter, J, Grabe, HJ, Hops, H, Jarvelin, MR, Viikari, J, Kähönen, M, Kendler, KS, Lehtimäki, T, Levinson, DF, Marazita, ML, Marchini, J, Melbye, M, Mitchell, BD, Murray, JC, Nöthen, MM, Penninx, BWJH, Raitakari, O, Rietschel, M, Rujescu, D, Samani, NJ, Sanders, AR, Schwartz, AG, Shete, S, Shi, J, Spitz, M, Stefansson, K, Swan, GE, Thorgeirsson, TE, Völzke, H, Wei, Q, Wichmann, HE, Amos, CI, Breslau, N, Cannon, DS, Ehringer, M, Grucza, RA, Hatsukami, D, Heath, AC, Johnson, EO, Kaprio, J, Madden, P, Martin, NG, Stevens, VL, Stitzel, JA, Weiss, RB, Kraft, P & Bierut, LJ 2012, 'Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers', Archives of general psychiatry, vol. 69, no. 8, pp. 854-860. https://doi.org/10.1001/archgenpsychiatry.2012.124

TY - JOUR

T1 - Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers

AU - Hartz, S.M.

AU - Short, S.E.

AU - Saccone, N.L.

AU - Culverhouse, R.

AU - Chen, L.

AU - Schwantes-An, T.H.

AU - Coon, H.

AU - Han, Y.

AU - Stephens, S.H.

AU - Sun, J.

AU - Chen, X.

AU - Ducci, F.

AU - Dueker, N.

AU - Franceschini, N.

AU - Frank, J.

AU - Geller, F.

AU - Gubjartsson, D.

AU - Hansel, N.N.

AU - Jiang, C.

AU - Keskitalo-Vuokko, K.

AU - Liu, Z.

AU - Lyytikäinen, L.P.

AU - Michel, M.

AU - Rawal, R.

AU - Rosenberger, A.

AU - Scheet, P.

AU - Shaffer, J.R.

AU - Teumer, A.

AU - Thompson, J.R.

AU - Vink, J.M.

AU - Vogelzangs, N.

AU - Wenzlaff, A.S.

AU - Wheeler, W.

AU - Xiao, X.

AU - Yang, B.Z.

AU - Aggen, S.H.

AU - Balmforth, A.J.

AU - Baumeister, S.E.

AU - Beaty, T.

AU - Bennett, S.

AU - Bergen, A.W.

AU - Boyd, H.A.

AU - Broms, U.

AU - Campbell, H.

AU - Chatterjee, N.

AU - Chen, J.

AU - Cheng, Y.C.

AU - Cichon, S.

AU - Couper, D.

AU - Cucca, F.

AU - Dick, D.M.

AU - Foroud, T.

AU - Furberg, H.

AU - Giegling, I.

AU - Gu, F.

AU - Hall, A.S.

AU - Hällfors, J.

AU - Han, S.

AU - Hartmann, A. M.

AU - Hayward, C.

AU - Heikkilä, K.

AU - Hewitt, J.K.

AU - Hottenga, J.J.

AU - Jensen, M.K.

AU - Jousilahti, P.

AU - Kaakinen, M.

AU - Kittner, S.J.

AU - Konte, B.

AU - Korhonen, T.

AU - Landi, M.T.

AU - Laatikainen, T.

AU - Leppert, M.

AU - Levy, S.M.

AU - Mathias, R.A.

AU - McNeil, D.W.

AU - Medland, S.E.

AU - Montgomery, G.W.

AU - Muley, T.

AU - Murray, T.

AU - Nauck, M.

AU - North, K.

AU - Pergadia, M.L.

AU - Polasek, O.

AU - Ramos, E.M.

AU - Ripatti, S.

AU - Risch, A.

AU - Ruczinski, I.

AU - Rudan, I.

AU - Salomaa, V.

AU - Schlessinger, D.

AU - Styrkársdóttir, U.

AU - Terracciano, A.

AU - Uda, M.

AU - Willemsen, G.

AU - Wu, X.

AU - Abecasis, G.R.

AU - Barnes, K.

AU - Bickeböller, H.

AU - Boerwinkle, E.

AU - Boomsma, D.I.

AU - Caporaso, N.

AU - Duan, J.

AU - Edenberg, H.J.

AU - Francks, C.

AU - Gejman, P.V.

AU - Gelernter, J.

AU - Grabe, H.J.

AU - Hops, H.

AU - Jarvelin, M.R.

AU - Viikari, J.

AU - Kähönen, M.

AU - Kendler, K.S.

AU - Lehtimäki, T.

AU - Levinson, D.F.

AU - Marazita, M.L.

AU - Marchini, J.

AU - Melbye, M.

AU - Mitchell, B.D.

AU - Murray, J.C.

AU - Nöthen, M.M.

AU - Penninx, B.W.J.H.

AU - Raitakari, O.

AU - Rietschel, M.

AU - Rujescu, D.

AU - Samani, N.J.

AU - Sanders, A.R.

AU - Schwartz, A.G.

AU - Shete, S.

AU - Shi, J.

AU - Spitz, M.

AU - Stefansson, K.

AU - Swan, G.E.

AU - Thorgeirsson, T.E.

AU - Völzke, H.

AU - Wei, Q.

AU - Wichmann, H.E.

AU - Amos, C.I.

AU - Breslau, N.

AU - Cannon, D.S.

AU - Ehringer, M.

AU - Grucza, R.A.

AU - Hatsukami, D.

AU - Heath, A.C.

AU - Johnson, E.O.

AU - Kaprio, J.

AU - Madden, P.

AU - Martin, N.G.

AU - Stevens, V.L.

AU - Stitzel, J.A.

AU - Weiss, R.B.

AU - Kraft, P.

AU - Bierut, L.J.

PY - 2012

Y1 - 2012

N2 - Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources: Primary data. Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DataExtraction: Uniform statistical analysis scripts were runlocally. Startingwith94 050ever-smokersfrom43studies, we extracted the heavy smokers (CPD>20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavyvs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01). Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. ©2012 American Medical Association. All rights reserved.

AB - Context: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources: Primary data. Study Selection: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DataExtraction: Uniform statistical analysis scripts were runlocally. Startingwith94 050ever-smokersfrom43studies, we extracted the heavy smokers (CPD>20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavyvs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36-1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR=1.27; 95% CI, 1.21-1.33, n=19 505) (P=.01). Conclusion: These results highlight an increased genetic vulnerability to smoking in early-onset smokers. ©2012 American Medical Association. All rights reserved.

U2 - https://doi.org/10.1001/archgenpsychiatry.2012.124

DO - https://doi.org/10.1001/archgenpsychiatry.2012.124

M3 - Article

C2 - 22868939

SN - 0003-990X

VL - 69

SP - 854

EP - 860

JO - Archives of general psychiatry

JF - Archives of general psychiatry

IS - 8

ER -