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Title: Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior.
Author(s): Thorgeirsson, T.E.; Gudbjartsson, D.F.; Surakka, I.; Vink, J.M. ; Amin, N.; Geller, F.; Sulem, P.; Rafnar, T.; Esko, T.; Walter, S.; Gieger, C.; Rawal, R.; Mangino, M.; Prokopenko, I.; Magi, R.; Keskitalo, K.; Gudjonsdottir, I.H.; Gretarsdottir, S.; Stefansson, H.; Thompson, J.R.; Aulchenko, Y.S.; Nelis, M.; Aben, K.K.H. ; Heijer, M. den ; Dirksen, A.; Ashraf, H.; Soranzo, N.; Valdes, A.M.; Steves, C.; Uitterlinden, A.G.; Hofman, A.; Tonjes, A.; Kovacs, P.; Hottenga, J.J.; Willemsen, G.; Vogelzangs, N.; Doring, A.; Dahmen, N.; Nitz, B.; Pergadia, M.L.; Saez, B.; Diego, V. De; Lezcano, V.; Garcia-Prats, M.D.; Ripatti, S.; Perola, M.; Kettunen, J.; Hartikainen, A.L.; Pouta, A.; Laitinen, J.; Isohanni, M.; Huei-Yi, S.; Allen, M.; Krestyaninova, M.; Hall, A.S.; Jones, G.T.; Rij, A.M. van; Mueller, T.; Dieplinger, B.; Haltmayer, M.; Jonsson, S.; Matthiasson, S.E.; Oskarsson, H.; Tyrfingsson, T.; Kiemeney, L.A.L.M. ; Mayordomo, J.I.; Lindholt, J.S.; Pedersen, J.H.; Franklin, W.A.; Wolf, H.; Montgomery, G.W.; Heath, A.C.; Martin, N.G.; Madden, P.A.F.; Giegling, I.; Rujescu, D.; Jarvelin, M.R.; Salomaa, V.; Stumvoll, M.; Spector, T.D.; Wichmann, H.E.; Metspalu, A.; Samani, N.J.; Penninx, B.W.J.H.; Oostra, B.A.; Boomsma, D.I. ; Tiemeier, H.; Duijn, C.M. van; Kaprio, J.; Gulcher, J.R.; McCarthy, M.I.; Peltonen, L.; Thorsteinsdottir, U.; Stefansson, K.
Publication year: 2010
Source: Nature Genetics, vol. 42, iss. 5, (2010), pp. 448-453
ISSN: 1061-4036
DOI: https://doi.org/10.1038/ng.573
Annotation: 1 mei 2010
Publication type: Article / Letter to editor

Please use this identifier to cite or link to this item : http://hdl.handle.net/2066/89305   http://hdl.handle.net/2066/89305

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Subject: IGMD 6: Hormonal regulation
NCEBP 1: Molecular epidemiology
NCEBP 2: Evaluation of complex medical interventions
ONCOL 5: Aetiology, screening and detection
ONCOL 5: Aetiology, screening and detection
Organization: Health Evidence
Endocrinology
Internal Medicine
Urology
Former Organization: Epidemiology, Biostatistics & HTA
Journal title:
Nature Genetics
Volume: vol. 42
Issue: iss. 5
Page start: p. 448
Page end: p. 453
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 x 10(-8)), including previously identified SNPs at 15q25 represented by rs1051730[A] (effect size = 0.80 CPD, P = 2.4 x 10(-69)), and SNPs at 19q13 and 8p11, represented by rs4105144[C] (effect size = 0.39 CPD, P = 2.2 x 10(-12)) and rs6474412-T (effect size = 0.29 CPD, P = 1.4 x 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).

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