Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior

Thorgeirsson, Thorgeir E., Gudbjartsson, Daniel F., Surakka, Ida, Vink, Jacqueline M., Amin, Najaf, Geller, Frank, Sulem, Patrick, Rafnar, Thorunn, Esko, Tōnu, Walter, Stefan, Gieger, Christian, Rawal, Rajesh, Mangino, Massimo, Prokopenko, Inga, Mägi, Reedik, Keskitalo, Kaisu, Gudjonsdottir, Iris H., Gretarsdottir, Solveig, Stefansson, Hreinn, Thompson, John R., Aulchenko, Yurii S., Nelis, Mari, Aben, Katja K., den Heijer, Martin, Dirksen, Asger, Ashraf, Haseem, Soranzo, Nicole, Valdes, Ana M., Steves, Claire, Uitterlinden, André G., Hofman, Albert, Tönjes, Anke, Kovacs, Peter, Hottenga, Jouke Jan, Willemsen, Gonneke, Vogelzangs, Nicole, Döring, Angela, Dahmen, Norbert, Nitz, Barbara, Pergadia, Michele L, Saez, Berta, De Diego, Veronica, Lezcano, Victoria, Garcia-Prats, Maria D., Ripatti, Samuli, Perola, Markus, Kettunen, Johannes, Hartikainen, Anna-Liisa, Pouta, Anneli, Laitinen, Jaana, Isohanni, Matti, Huei-Yi, Shen, Allen, Maxine, Krestyaninova, Maria, Hall, Alistair S., Jones, Gregory T., van Rij, Andre M., Mueller, Thomas, Dieplinger, Benjamin, Haltmayer, Meinhard, Jonsson, Steinn, Matthiasson, Stefan E., Oskarsson, Hogni, Tyrfingsson, Thorarinn, Kiemeney, Lambertus A., Mayordomo, Jose I., Lindholt, Jes S., Pedersen, Jesper Holst, Franklin, Wilbur A., Wolf, Holly, Montgomery, Grant W., Heath, Andrew C., Martin, Nicholas G., Madden, Pamela A. F., Giegling, Ina, Rujescu, Dan, Järvelin, Marjo-Riitta, Salomaa, Veikko, Stumvoll, Michael, Spector, Tim D., Wichmann, H.-Erich, Metspalu, Andres, Samani, Nilesh J., Penninx, Brenda W., Oostra, Ben A., Boomsma, Dorret I., Tiemeier, Henning, van Duijn, Cornelia M., Kaprio, Jaakko, Gulcher, Jeffrey R., The ENGAGE Consortium, McCarthy, Mark I., Peltonen, Leena, Thorsteinsdottir, Unnur and Stefansson, Kari (2010) Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nature Genetics, 42 5: 448-454. doi:10.1038/ng.573

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Author Thorgeirsson, Thorgeir E.
Gudbjartsson, Daniel F.
Surakka, Ida
Vink, Jacqueline M.
Amin, Najaf
Geller, Frank
Sulem, Patrick
Rafnar, Thorunn
Esko, Tōnu
Walter, Stefan
Gieger, Christian
Rawal, Rajesh
Mangino, Massimo
Prokopenko, Inga
Mägi, Reedik
Keskitalo, Kaisu
Gudjonsdottir, Iris H.
Gretarsdottir, Solveig
Stefansson, Hreinn
Thompson, John R.
Aulchenko, Yurii S.
Nelis, Mari
Aben, Katja K.
den Heijer, Martin
Dirksen, Asger
Ashraf, Haseem
Soranzo, Nicole
Valdes, Ana M.
Steves, Claire
Uitterlinden, André G.
Hofman, Albert
Tönjes, Anke
Kovacs, Peter
Hottenga, Jouke Jan
Willemsen, Gonneke
Vogelzangs, Nicole
Döring, Angela
Dahmen, Norbert
Nitz, Barbara
Pergadia, Michele L
Saez, Berta
De Diego, Veronica
Lezcano, Victoria
Garcia-Prats, Maria D.
Ripatti, Samuli
Perola, Markus
Kettunen, Johannes
Hartikainen, Anna-Liisa
Pouta, Anneli
Laitinen, Jaana
Isohanni, Matti
Huei-Yi, Shen
Allen, Maxine
Krestyaninova, Maria
Hall, Alistair S.
Jones, Gregory T.
van Rij, Andre M.
Mueller, Thomas
Dieplinger, Benjamin
Haltmayer, Meinhard
Jonsson, Steinn
Matthiasson, Stefan E.
Oskarsson, Hogni
Tyrfingsson, Thorarinn
Kiemeney, Lambertus A.
Mayordomo, Jose I.
Lindholt, Jes S.
Pedersen, Jesper Holst
Franklin, Wilbur A.
Wolf, Holly
Montgomery, Grant W.
Heath, Andrew C.
Martin, Nicholas G.
Madden, Pamela A. F.
Giegling, Ina
Rujescu, Dan
Järvelin, Marjo-Riitta
Salomaa, Veikko
Stumvoll, Michael
Spector, Tim D.
Wichmann, H.-Erich
Metspalu, Andres
Samani, Nilesh J.
Penninx, Brenda W.
Oostra, Ben A.
Boomsma, Dorret I.
Tiemeier, Henning
van Duijn, Cornelia M.
Kaprio, Jaakko
Gulcher, Jeffrey R.
The ENGAGE Consortium
McCarthy, Mark I.
Peltonen, Leena
Thorsteinsdottir, Unnur
Stefansson, Kari
Title Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior
Formatted title
Sequence variants at CHRNB3CHRNA6 and CYP2A6 affect smoking behavior
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2010-05
Sub-type Article (original research)
DOI 10.1038/ng.573
Volume 42
Issue 5
Start page 448
End page 454
Total pages 7
Editor Myles Axton
Place of publication New York, NY, U.S.A.
Publisher Nature Publishing Group
Collection year 2011
Language eng
Formatted abstract
Smoking is a common risk factor for many diseases. We conducted genome-wide association meta-analyses for the number of cigarettes smoked per day (CPD) in smokers (n = 31,266) and smoking initiation (n = 46,481) using samples from the ENGAGE Consortium. In a second stage, we tested selected SNPs with in silico replication in the Tobacco and Genetics (TAG) and Glaxo Smith Kline (Ox-GSK) consortia cohorts (n = 45,691 smokers) and assessed some of those in a third sample of European ancestry (n = 9,040). Variants in three genomic regions associated with CPD (P < 5 × 10−8), including previously identified SNPs at 15q25 represented by rs1051730[A] (effect size = 0.80 CPD, P = 2.4 × 10−69), and SNPs at 19q13 and 8p11, represented by rs4105144[C] (effect size = 0.39 CPD, P = 2.2 × 10−12) and rs6474412-T (effect size = 0.29 CPD, P = 1.4 × 10−8), respectively. Among the genes at the two newly associated loci are genes encoding nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (CHRNB3 and CHRNA6), all of which have been highlighted in previous studies of smoking and nicotine dependence. Nominal associations with lung cancer were observed at both 8p11 (rs6474412[T], odds ratio (OR) = 1.09, P = 0.04) and 19q13 (rs4105144[C], OR = 1.12, P = 0.0006).
© 2010 Nature America, Inc. All rights reserved.
Keyword Genome-wide association
Nicotinic acetylcholine-receptors
Lung-cancer
Susceptibility locus
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Wed, 30 Mar 2011, 15:44:30 EST by Debbie Banks on behalf of Medicine - Royal Brisbane and Women's Hospital