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

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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. ©2012 American Medical Association. All rights reserved.
Original languageEnglish
Pages (from-to)854-860
JournalArchives of general psychiatry
Volume69
Issue number8
DOIs
Publication statusPublished - 2012

Cohort Studies

  • Netherlands Twin Register (NTR)

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