Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior

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

doi:10.1038/ng.573

Back

Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior

Journal article

Peer reviewed

Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior

Thorgeir E. Thorgeirsson, Daniel F. Gudbjartsson, Ida Surakka, Jacqueline M. Vink, Najaf Amin, Frank Geller, Patrick Sulem, Thorunn Rafnar, Tonu Esko, Stefan Walter, …

Nature genetics, Vol.42(5), pp.448-U135

01/05/2010

DOI: https://doi.org/10.1038/ng.573

PMID: 20418888

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Smoking is a common risk factor for many diseases(1). 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 dependence2-4. 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).

Metrics

1 Record Views

538 Times Cited - Web of Science

See more details

Details

Title: Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior
Creators: Thorgeir E. Thorgeirsson - deCODE Genetics
Daniel F. Gudbjartsson - deCODE Genet, Reykjavik, Iceland
Ida Surakka - Institute for Molecular Medicine Finland
Jacqueline M. Vink - Vrije Universiteit Amsterdam
Najaf Amin - Erasmus MC
Frank Geller - deCODE Genetics
Patrick Sulem - deCODE Genetics
Thorunn Rafnar - deCODE Genet, Reykjavik, Iceland
Tonu Esko - University of Tartu
Stefan Walter - Erasmus MC
Christian Gieger - Helmholtz Zentrum München
Rajesh Rawal - Helmholtz Zentrum München
Massimo Mangino - St Thomas' Hospital
Inga Prokopenko - Oxford Centre for Diabetes, Endocrinology and Metabolism
Reedik Magi - Oxford Centre for Diabetes, Endocrinology and Metabolism
Kaisu Keskitalo - University of Helsinki
Iris H. Gudjonsdottir - deCODE Genetics
Solveig Gretarsdottir - deCODE Genetics
Hreinn Stefansson - deCODE Genetics
John R. Thompson - University of Leicester
Yurii S. Aulchenko - Erasmus MC
Mari Nelis - University of Tartu
Katja K. Aben - Radboud University Nijmegen
Martin den Heijer - Radboud University Nijmegen
Asger Dirksen - Gentofte Hospital
Haseem Ashraf - Gentofte Hospital
Nicole Soranzo - St Thomas' Hospital
Ana M. Valdes - St Thomas' Hospital
Claire Steves - St Thomas' Hospital
Andre G. Uitterlinden - Erasmus MC
Albert Hofman - Erasmus MC
Anke Tonjes - Leipzig University
Peter Kovacs - Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany
Jouke Jan Hottenga - Vrije Universiteit Amsterdam
Gonneke Willemsen - Vrije Universiteit Amsterdam
Nicole Vogelzangs - Amsterdam UMC Location VUmc
Angela Doering - Helmholtz Zentrum München
Norbert Dahmen - Johannes Gutenberg University Mainz
Barbara Nitz - Helmholtz Zentrum München
Michele L. Pergadia - Washington University in St. Louis
Berta Saez - Instituto de Nanociencia y Materiales de Aragón
Veronica De Diego - Hospital San Pedro
Victoria Lezcano - Hospital San Pedro
Maria D. Garcia-Prats - Hospital General San Jorge
Samuli Ripatti - Finnish Institute for Health and Welfare
Markus Perola - Finnish Institute for Health and Welfare
Johannes Kettunen - Wellcome Sanger Institute
Anna-Liisa Hartikainen - Hosp San Pedro, Div Dermatol, Logrono, Spain
Anneli Pouta - Finnish Institute for Health and Welfare
Jaana Laitinen - Finnish Inst Occupat Hlth, Oulu, Finland
Matti Isohanni - University of Oulu
Shen Huei-Yi - University of Helsinki
Maxine Allen - Oxford Centre for Diabetes, Endocrinology and Metabolism
Maria Krestyaninova - European Bioinformatics Institute
Alistair S. Hall - University of Leeds
Gregory T. Jones - University of Otago
Andre M. van Rij - University of Otago
Thomas Mueller - Convent Hospital of the Brothers of Saint John of God
Benjamin Dieplinger - Convent Hospital of the Brothers of Saint John of God
Meinhard Haltmayer - Convent Hospital of the Brothers of Saint John of God
Steinn Jonsson - Reykjavík University
Stefan E. Matthiasson - University of Iceland
Hogni Oskarsson - Therapeia, Reykjavik, Iceland
Thorarinn Tyrfingsson - College Station Medical Center
Lambertus A. Kiemeney - Netherlands Comprehensive Cancer Organisation
Jose I. Mayordomo - Universidad de Zaragoza
Jes S. Lindholt - Regionshospitalet Viborg
Jesper Holst Pedersen - University of Copenhagen
Wilbur A. Franklin - University of Colorado Denver
Holly Wolf - Colorado School of Public Health
Grant W. Montgomery - QIMR Berghofer Medical Research Institute
Andrew C. Heath - Washington University in St. Louis
Nicholas G. Martin - QIMR Berghofer Medical Research Institute
Pamela A. F. Madden - Washington University in St. Louis
Ina Giegling - Ludwig-Maximilians-Universität München
Dan Rujescu - Ludwig-Maximilians-Universität München
Marjo-Riitta Jaervelin - Natl Inst Hlth & Welf, Lifecourse & Serv Dept, Oulu, Finland
Veikko Salomaa - Finnish Institute for Health and Welfare
Michael Stumvoll - Leipzig University
Tim D. Spector - St Thomas' Hospital
H-Erich Wichmann - Helmholtz Zentrum München
Andres Metspalu - Estonian Biocentre
Nilesh J. Samani - Glenfield Hospital
Brenda W. Penninx - University of Amsterdam
Ben A. Oostra - Erasmus MC
Dorret I. Boomsma - Vrije Universiteit Amsterdam
Henning Tiemeier - Erasmus MC
Cornelia M. van Duijn - Erasmus MC
Jaakko Kaprio - Finnish Institute for Health and Welfare
Jeffrey R. Gulcher - deCODE Genetics
Mark I. McCarthy - Wellcome Centre for Human Genetics
Leena Peltonen - Wellcome Sanger Institute
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
Kari Stefansson - University of Iceland
ENGAGE Consortium
Publication Details: Nature genetics, Vol.42(5), pp.448-U135
Publisher: Springer Nature
Number of pages: 7
Date published: 01/05/2010
Grant note: R01DA017932 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA LSHM-CT-2004-005166; HEALTH-F42007-201413 / European Commission; European Union (EU); European Commission Joint Research Centre
Identifiers: 99928782102346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior

Abstract

Metrics

Details

Usage Policy