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Get Free AccessNeuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype.
Sarah H. Stephens, Sarah M. Hartz, Nicole R. Hoft, Nancy L. Saccone, Robin Corley, John K. Hewitt, Christian J. Hopfer, Naomi Breslau, Hilary Coon, Xiangning Chen, Francesca Ducci, Nicole Dueker, Nora Franceschini, Josef Frank, Younghun Han, Nadia N. Hansel, Chenhui Jiang, Tellervo Korhonen, Penelope A. Lind, Jason Liu, Leo‐Pekka Lyytikäinen, Martha Michel, John R. Shaffer, Susan E. Short, Juzhong Sun, Alexander Teumer, John R. Thompson, Nicole Vogelzangs, Jacqueline M. Vink, Angela S. Wenzlaff, William Wheeler, Bao‐Zhu Yang, Steven H. Aggen, Anthony J. Balmforth, Sebastian E. Baumeister, Terri H. Beaty, Daniel J. Benjamin, Andrew W. Bergen, Ulla Broms, David Cesarini, Nilanjan Chatterjee, Jingchun Chen, Yu‐Ching Cheng, Sven Cichon, David Couper, Francesco Cucca, Danielle M. Dick, Tatiana Foroud, Helena Furberg, Ina Giegling, Nathan A. Gillespie, Fangyi Gu, Alistair S. Hall, Jenni Hällfors, Shizhong Han, Annette M. Hartmann, Kauko Heikkilä, Ian B. Hickie, Jouke‐Jan Hottenga, Jari Lahti, Marika Kaakinen, Mika Kähönen, Philipp Koellinger, S. J. Kittner, Bettina Konte, Maria‐Teresa Landi, Tiina Laatikainen, Mark Leppert, Steven M. Levy, Rasika A. Mathias, Daniel W. McNeil, Sarah E. Medland, Grant W. Montgomery, Tanda Murray, Matthias Nauck, Kari E. North, Peter D. Paré, Michele L. Pergadia, Ingo Ruczinski, Veikko Salomaa, Jorma Viikari, Gonneke Willemsen, Kathleen C. Barnes, Eric Boerwinkle, Dorret I. Boomsma, Neil E. Caporaso, Howard J. Edenberg, Clyde Francks, Joel Gelernter, Hans J. Grabe, Hyman Hops, Paul M Ridker, Magnus Johannesson, Kenneth S. Kendler, Terho Lehtimäki, Patrik K. E. Magnusson, Mary L. Marazita, Jonathan Marchini, Braxton D. Mitchell, Markus M. Nöthen (2013). Distinct Loci in the <i>CHRNA5</i>/<i>CHRNA3</i>/<i>CHRNB4</i> Gene Cluster Are Associated With Onset of Regular Smoking. , 37(8), DOI: https://doi.org/10.1002/gepi.21760.
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Type
Article
Year
2013
Authors
100
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1002/gepi.21760
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