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 journalArticle

48 Scopus citations

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 languageEnglish (US)
Pages (from-to)854-861
Number of pages8
JournalArchives of general psychiatry
Volume69
Issue number8
DOIs
StatePublished - Aug 1 2012

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ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Cite this

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