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

Sarah M. Hartz; Susan E. Short; Nancy L. Saccone; Robert Culverhouse; Li Shiun Chen; Tae Hwi Schwantes-An; Hilary Coon; Younghun Han; Sarah H. Stephens; Juzhong Sun; Xiangning Chen; Francesca Ducci; Nicole Dueker; Nora Franceschini; Josef Frank; Frank Geller; Daniel Guobjartsson; Nadia N. Hansel; Chenhui Jiang; Kaisu Keskitalo-Vuokko; Zhen Liu; Leo Pekka Lyytikäinen; Martha Michel; Rajesh Rawal; Albert Rosenberger; Paul Scheet; John R. Shaffer; Alexander Teumer; John R. Thompson; Jacqueline M. Vink; Nicole Vogelzangs; Angela S. Wenzlaff; William Wheeler; Xiangjun Xiao; Bao Zhu Yang; Steven H. Aggen; Anthony J. Balmforth; Sebastian E. Baumeister; Terri Beaty; Siiri Bennett; Andrew W. Bergen; Heather A. Boyd; Ulla Broms; Harry Campbell; Nilanjan Chatterjee; Jingchun Chen; Yu Ching Cheng; Sven Cichon; David Couper; Francesco Cucca; Danielle M. Dick; Tatiana Foroud; Helena Furberg; Ina Giegling; Fangyi Gu; Alistair S. Hall; Jenni Hällfors; Shizhong Han; Annette M. Hartmann; Caroline Hayward; Kauko Heikkilä; John K. Hewitt; Jouke Jan Hottenga; Majken K. Jensen; Pekka Jousilahti; Marika Kaakinen; Steven J. Kittner; Bettina Konte; Tellervo Korhonen; Maria Teresa Landi; Tiina Laatikainen; Mark Leppert; Steven M. Levy; Rasika A. Mathias; Daniel W. McNeil; Sarah E. Medland; Grant W. Montgomery; Thomas Muley; Tanda Murray; Matthias Nauck; Kari North; Michele Pergadia; Ozren Polasek; Erin M. Ramos; Samuli Ripatti; Angela Risch; Ingo Ruczinski; Igor Rudan; Veikko Salomaa; David Schlessinger; Unnur Styrkársdóttir; Antonio Terracciano; Manuela Uda; Gonneke Willemsen; Xifeng Wu; Goncalo Abecasis; Kathleen Barnes; Heike Bickeböller; Eric Boerwinkle; Dorret I. Boomsma; Neil Caporaso; Jubao Duan; Howard J. Edenberg; Clyde Francks; Pablo V. Gejman; Joel Gelernter; Hans Jörgen Grabe; Hyman Hops; Marjo Riitta Jarvelin; Jorma Viikari; Mika Kähönen; Kenneth S. Kendler; Terho Lehtimäki; Douglas F. Levinson; Mary L. Marazita; Jonathan Marchini; Mads Melbye; Braxton D. Mitchell; Jeffrey C. Murray; Markus M. Nöthen; Brenda W. Penninx; Olli Raitakari; Marcella Rietschel; Dan Rujescu; Nilesh J. Samani; Alan R. Sanders; Ann G. Schwartz; Sanjay Shete; Jianxin Shi; Margaret Spitz; Kari Stefansson; Gary E. Swan; Thorgeir Thorgeirsson; Henry Völzke; Qingyi Wei; H. Erich Wichmann; Christopher I. Amos; Naomi Breslau; Dale S. Cannon; Marissa Ehringer; Richard Grucza; Dorothy Hatsukami; Andrew Heath; Eric O. Johnson; Jaakko Kaprio; Pamela Madden; Nicholas G. Martin; Victoria L. Stevens; Jerry A. Stitzel; Robert B. Weiss; Peter Kraft; Laura J. Bierut

doi:10.1001/archgenpsychiatry.2012.124

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

Sarah M. Hartz, Susan E. Short, Nancy L. Saccone, Robert Culverhouse, Li Shiun Chen, Tae Hwi Schwantes-An, Hilary Coon, Younghun Han, Sarah H. Stephens, Juzhong Sun, Xiangning Chen, Francesca Ducci, Nicole Dueker, Nora Franceschini, Josef Frank, Frank Geller, Daniel Guobjartsson, Nadia N. Hansel, Chenhui Jiang, Kaisu Keskitalo-VuokkoZhen Liu, Leo Pekka Lyytikäinen, Martha Michel, Rajesh Rawal, Albert Rosenberger, Paul Scheet, John R. Shaffer, Alexander Teumer, John R. Thompson, Jacqueline M. Vink, Nicole Vogelzangs, Angela S. Wenzlaff, William Wheeler, Xiangjun Xiao, Bao Zhu Yang, Steven H. Aggen, Anthony J. Balmforth, Sebastian E. Baumeister, Terri Beaty, Siiri Bennett, Andrew W. Bergen, Heather A. Boyd, Ulla Broms, Harry Campbell, Nilanjan Chatterjee, Jingchun Chen, Yu Ching Cheng, Sven Cichon, David Couper, Francesco Cucca, Danielle M. Dick, Tatiana Foroud, Helena Furberg, Ina Giegling, Fangyi Gu, Alistair S. Hall, Jenni Hällfors, Shizhong Han, Annette M. Hartmann, Caroline Hayward, Kauko Heikkilä, John K. Hewitt, Jouke Jan Hottenga, Majken K. Jensen, Pekka Jousilahti, Marika Kaakinen, Steven J. Kittner, Bettina Konte, Tellervo Korhonen, Maria Teresa Landi, Tiina Laatikainen, Mark Leppert, Steven M. Levy, Rasika A. Mathias, Daniel W. McNeil, Sarah E. Medland, Grant W. Montgomery, Thomas Muley, Tanda Murray, Matthias Nauck, Kari North, Michele Pergadia, Ozren Polasek, Erin M. Ramos, Samuli Ripatti, Angela Risch, Ingo Ruczinski, Igor Rudan, Veikko Salomaa, David Schlessinger, Unnur Styrkársdóttir, Antonio Terracciano, Manuela Uda, Gonneke Willemsen, Xifeng Wu, Goncalo Abecasis, Kathleen Barnes, Heike Bickeböller, Eric Boerwinkle, Dorret I. Boomsma, Neil Caporaso, Jubao Duan, Howard J. Edenberg, Clyde Francks, Pablo V. Gejman, Joel Gelernter, Hans Jörgen Grabe, Hyman Hops, Marjo Riitta Jarvelin, Jorma Viikari, Mika Kähönen, Kenneth S. Kendler, Terho Lehtimäki, Douglas F. Levinson, Mary L. Marazita, Jonathan Marchini, Mads Melbye, Braxton D. Mitchell, Jeffrey C. Murray, Markus M. Nöthen, Brenda W. Penninx, Olli Raitakari, Marcella Rietschel, Dan Rujescu, Nilesh J. Samani, Alan R. Sanders, Ann G. Schwartz, Sanjay Shete, Jianxin Shi, Margaret Spitz, Kari Stefansson, Gary E. Swan, Thorgeir Thorgeirsson, Henry Völzke, Qingyi Wei, H. Erich Wichmann, Christopher I. Amos, Naomi Breslau, Dale S. Cannon, Marissa Ehringer, Richard Grucza, Dorothy Hatsukami, Andrew Heath, Eric O. Johnson, Jaakko Kaprio, Pamela Madden, Nicholas G. Martin, Victoria L. Stevens, Jerry A. Stitzel, Robert B. Weiss, Peter Kraft, Laura J. Bierut

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

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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.

Original language	English
Pages (from-to)	854-861
Number of pages	8
Journal	Archives of General Psychiatry
Volume	69
Issue number	8
DOIs	https://doi.org/10.1001/archgenpsychiatry.2012.124
State	Published - Aug 2012

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10.1001/archgenpsychiatry.2012.124

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Hartz, S. M., Short, S. E., Saccone, N. L., Culverhouse, R., Chen, L. S., 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., Guobjartsson, 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), 854-861. https://doi.org/10.1001/archgenpsychiatry.2012.124

@article{61e193a9e17640899b4621790f65370a,

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.",

author = "Hartz, {Sarah M.} and Short, {Susan E.} and Saccone, {Nancy L.} and Robert Culverhouse and Chen, {Li Shiun} and Schwantes-An, {Tae Hwi} and Hilary Coon and Younghun Han and Stephens, {Sarah H.} and Juzhong Sun and Xiangning Chen and Francesca Ducci and Nicole Dueker and Nora Franceschini and Josef Frank and Frank Geller and Daniel Guobjartsson and Hansel, {Nadia N.} and Chenhui Jiang and Kaisu Keskitalo-Vuokko and Zhen Liu and Lyytik{\"a}inen, {Leo Pekka} and Martha Michel and Rajesh Rawal and Albert Rosenberger and Paul Scheet and Shaffer, {John R.} and Alexander Teumer and Thompson, {John R.} and Vink, {Jacqueline M.} and Nicole Vogelzangs and Wenzlaff, {Angela S.} and William Wheeler and Xiangjun Xiao and Yang, {Bao Zhu} and Aggen, {Steven H.} and Balmforth, {Anthony J.} and Baumeister, {Sebastian E.} and Terri Beaty and Siiri Bennett and Bergen, {Andrew W.} and Boyd, {Heather A.} and Ulla Broms and Harry Campbell and Nilanjan Chatterjee and Jingchun Chen and Cheng, {Yu Ching} and Sven Cichon and David Couper and Francesco Cucca and Dick, {Danielle M.} and Tatiana Foroud and Helena Furberg and Ina Giegling and Fangyi Gu and Hall, {Alistair S.} and Jenni H{\"a}llfors and Shizhong Han and Hartmann, {Annette M.} and Caroline Hayward and Kauko Heikkil{\"a} and Hewitt, {John K.} and Hottenga, {Jouke Jan} and Jensen, {Majken K.} and Pekka Jousilahti and Marika Kaakinen and Kittner, {Steven J.} and Bettina Konte and Tellervo Korhonen and Landi, {Maria Teresa} and Tiina Laatikainen and Mark Leppert and Levy, {Steven M.} and Mathias, {Rasika A.} and McNeil, {Daniel W.} and Medland, {Sarah E.} and Montgomery, {Grant W.} and Thomas Muley and Tanda Murray and Matthias Nauck and Kari North and Michele Pergadia and Ozren Polasek and Ramos, {Erin M.} and Samuli Ripatti and Angela Risch and Ingo Ruczinski and Igor Rudan and Veikko Salomaa and David Schlessinger and Unnur Styrk{\'a}rsd{\'o}ttir and Antonio Terracciano and Manuela Uda and Gonneke Willemsen and Xifeng Wu and Goncalo Abecasis and Kathleen Barnes and Heike Bickeb{\"o}ller and Eric Boerwinkle and Boomsma, {Dorret I.} and Neil Caporaso and Jubao Duan and Edenberg, {Howard J.} and Clyde Francks and Gejman, {Pablo V.} and Joel Gelernter and Grabe, {Hans J{\"o}rgen} and Hyman Hops and Jarvelin, {Marjo Riitta} and Jorma Viikari and Mika K{\"a}h{\"o}nen and Kendler, {Kenneth S.} and Terho Lehtim{\"a}ki and Levinson, {Douglas F.} and Marazita, {Mary L.} and Jonathan Marchini and Mads Melbye and Mitchell, {Braxton D.} and Murray, {Jeffrey C.} and N{\"o}then, {Markus M.} and Penninx, {Brenda W.} and Olli Raitakari and Marcella Rietschel and Dan Rujescu and Samani, {Nilesh J.} and Sanders, {Alan R.} and Schwartz, {Ann G.} and Sanjay Shete and Jianxin Shi and Margaret Spitz and Kari Stefansson and Swan, {Gary E.} and Thorgeir Thorgeirsson and Henry V{\"o}lzke and Qingyi Wei and Wichmann, {H. Erich} and Amos, {Christopher I.} and Naomi Breslau and Cannon, {Dale S.} and Marissa Ehringer and Richard Grucza and Dorothy Hatsukami and Andrew Heath and Johnson, {Eric O.} and Jaakko Kaprio and Pamela Madden and Martin, {Nicholas G.} and Stevens, {Victoria L.} and Stitzel, {Jerry A.} and Weiss, {Robert B.} and Peter Kraft and Bierut, {Laura J.}",

year = "2012",

month = aug,

doi = "10.1001/archgenpsychiatry.2012.124",

language = "English",

volume = "69",

pages = "854--861",

journal = "Archives of General Psychiatry",

issn = "0003-990X",

number = "8",

}

Hartz, SM, Short, SE, Saccone, NL, Culverhouse, R, Chen, LS, Schwantes-An, TH, Coon, H, Han, Y, Stephens, SH, Sun, J, Chen, X, Ducci, F, Dueker, N, Franceschini, N, Frank, J, Geller, F, Guobjartsson, 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, M, 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, G, 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, BW, Raitakari, O, Rietschel, M, Rujescu, D, Samani, NJ, Sanders, AR, Schwartz, AG, Shete, S, Shi, J, Spitz, M, Stefansson, K, Swan, GE, Thorgeirsson, T, Völzke, H, Wei, Q, Wichmann, HE, Amos, CI, Breslau, N, Cannon, DS, Ehringer, M, Grucza, R, Hatsukami, D, Heath, A, 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. 854-861. https://doi.org/10.1001/archgenpsychiatry.2012.124

TY - JOUR

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

AU - Hartz, Sarah M.

AU - Short, Susan E.

AU - Saccone, Nancy L.

AU - Culverhouse, Robert

AU - Chen, Li Shiun

AU - Schwantes-An, Tae Hwi

AU - Coon, Hilary

AU - Han, Younghun

AU - Stephens, Sarah H.

AU - Sun, Juzhong

AU - Chen, Xiangning

AU - Ducci, Francesca

AU - Dueker, Nicole

AU - Franceschini, Nora

AU - Frank, Josef

AU - Geller, Frank

AU - Guobjartsson, Daniel

AU - Hansel, Nadia N.

AU - Jiang, Chenhui

AU - Keskitalo-Vuokko, Kaisu

AU - Liu, Zhen

AU - Lyytikäinen, Leo Pekka

AU - Michel, Martha

AU - Rawal, Rajesh

AU - Rosenberger, Albert

AU - Scheet, Paul

AU - Shaffer, John R.

AU - Teumer, Alexander

AU - Thompson, John R.

AU - Vink, Jacqueline M.

AU - Vogelzangs, Nicole

AU - Wenzlaff, Angela S.

AU - Wheeler, William

AU - Xiao, Xiangjun

AU - Yang, Bao Zhu

AU - Aggen, Steven H.

AU - Balmforth, Anthony J.

AU - Baumeister, Sebastian E.

AU - Beaty, Terri

AU - Bennett, Siiri

AU - Bergen, Andrew W.

AU - Boyd, Heather A.

AU - Broms, Ulla

AU - Campbell, Harry

AU - Chatterjee, Nilanjan

AU - Chen, Jingchun

AU - Cheng, Yu Ching

AU - Cichon, Sven

AU - Couper, David

AU - Cucca, Francesco

AU - Dick, Danielle M.

AU - Foroud, Tatiana

AU - Furberg, Helena

AU - Giegling, Ina

AU - Gu, Fangyi

AU - Hall, Alistair S.

AU - Hällfors, Jenni

AU - Han, Shizhong

AU - Hartmann, Annette M.

AU - Hayward, Caroline

AU - Heikkilä, Kauko

AU - Hewitt, John K.

AU - Hottenga, Jouke Jan

AU - Jensen, Majken K.

AU - Jousilahti, Pekka

AU - Kaakinen, Marika

AU - Kittner, Steven J.

AU - Konte, Bettina

AU - Korhonen, Tellervo

AU - Landi, Maria Teresa

AU - Laatikainen, Tiina

AU - Leppert, Mark

AU - Levy, Steven M.

AU - Mathias, Rasika A.

AU - McNeil, Daniel W.

AU - Medland, Sarah E.

AU - Montgomery, Grant W.

AU - Muley, Thomas

AU - Murray, Tanda

AU - Nauck, Matthias

AU - North, Kari

AU - Pergadia, Michele

AU - Polasek, Ozren

AU - Ramos, Erin M.

AU - Ripatti, Samuli

AU - Risch, Angela

AU - Ruczinski, Ingo

AU - Rudan, Igor

AU - Salomaa, Veikko

AU - Schlessinger, David

AU - Styrkársdóttir, Unnur

AU - Terracciano, Antonio

AU - Uda, Manuela

AU - Willemsen, Gonneke

AU - Wu, Xifeng

AU - Abecasis, Goncalo

AU - Barnes, Kathleen

AU - Bickeböller, Heike

AU - Boerwinkle, Eric

AU - Boomsma, Dorret I.

AU - Caporaso, Neil

AU - Duan, Jubao

AU - Edenberg, Howard J.

AU - Francks, Clyde

AU - Gejman, Pablo V.

AU - Gelernter, Joel

AU - Grabe, Hans Jörgen

AU - Hops, Hyman

AU - Jarvelin, Marjo Riitta

AU - Viikari, Jorma

AU - Kähönen, Mika

AU - Kendler, Kenneth S.

AU - Lehtimäki, Terho

AU - Levinson, Douglas F.

AU - Marazita, Mary L.

AU - Marchini, Jonathan

AU - Melbye, Mads

AU - Mitchell, Braxton D.

AU - Murray, Jeffrey C.

AU - Nöthen, Markus M.

AU - Penninx, Brenda W.

AU - Raitakari, Olli

AU - Rietschel, Marcella

AU - Rujescu, Dan

AU - Samani, Nilesh J.

AU - Sanders, Alan R.

AU - Schwartz, Ann G.

AU - Shete, Sanjay

AU - Shi, Jianxin

AU - Spitz, Margaret

AU - Stefansson, Kari

AU - Swan, Gary E.

AU - Thorgeirsson, Thorgeir

AU - Völzke, Henry

AU - Wei, Qingyi

AU - Wichmann, H. Erich

AU - Amos, Christopher I.

AU - Breslau, Naomi

AU - Cannon, Dale S.

AU - Ehringer, Marissa

AU - Grucza, Richard

AU - Hatsukami, Dorothy

AU - Heath, Andrew

AU - Johnson, Eric O.

AU - Kaprio, Jaakko

AU - Madden, Pamela

AU - Martin, Nicholas G.

AU - Stevens, Victoria L.

AU - Stitzel, Jerry A.

AU - Weiss, Robert B.

AU - Kraft, Peter

AU - Bierut, Laura J.

PY - 2012/8

Y1 - 2012/8

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84865562672&partnerID=8YFLogxK

U2 - 10.1001/archgenpsychiatry.2012.124

DO - 10.1001/archgenpsychiatry.2012.124

M3 - Article

C2 - 22868939

AN - SCOPUS:84865562672

VL - 69

SP - 854

EP - 861

JO - Archives of General Psychiatry

JF - Archives of General Psychiatry

SN - 0003-990X

IS - 8

ER -

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

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