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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Genome-wide meta-analyses identify multiple loci associated with smoking behavior

Author

  • Helena Furberg
  • YunJung Kim
  • Jennifer Dackor
  • Eric Boerwinkle
  • Nora Franceschini
  • Diego Ardissino
  • Luisa Bernardinelli
  • Pier M. Mannucci
  • Francesco Mauri
  • Piera A. Merlini
  • Devin Absher
  • Themistocles L. Assimes
  • Stephen P. Fortmann
  • Carlos Iribarren
  • Joshua W. Knowles
  • Thomas Quertermous
  • Luigi Ferrucci
  • Toshiko Tanaka
  • Joshua C. Bis
  • Curt D. Furberg
  • Talin Haritunians
  • Barbara McKnight
  • Bruce M. Psaty
  • Kent D. Taylor
  • Evan L. Thacker
  • Peter Almgren
  • Leif Groop
  • Claes Ladenvall
  • Michael Boehnke
  • Anne U. Jackson
  • Karen L. Mohlke
  • Heather M. Stringham
  • Jaakko Tuomilehto
  • Emelia J. Benjamin
  • Shih-Jen Hwang
  • Daniel Levy
  • Sarah Rosner Preis
  • Ramachandran S. Vasan
  • Jubao Duan
  • Pablo V. Gejman
  • Douglas F. Levinson
  • Alan R. Sanders
  • Jianxin Shi
  • Esther H. Lips
  • James D. Mckay
  • Antonio Agudo
  • Luigi Barzan
  • Vladimir Bencko
  • Simone Benhamou
  • Xavier Castellsague
  • Cristina Canova
  • David I. Conway
  • Eleonora Fabianova
  • Lenka Foretova
  • Vladimir Janout
  • Claire M. Healy
  • Ivana Holcatova
  • Kristina Kjaerheim
  • Pagona Lagiou
  • Jolanta Lissowska
  • Ray Lowry
  • Tatiana V. Macfarlane
  • Dana Mates
  • Lorenzo Richiardi
  • Peter Rudnai
  • Neonilia Szeszenia-Dabrowska
  • David Zaridze
  • Ariana Znaor
  • Mark Lathrop
  • Paul Brennan
  • Stefania Bandinelli
  • Timothy M. Frayling
  • Jack M. Guralnik
  • Yuri Milaneschi
  • John R. B. Perry
  • David Altshuler
  • Roberto Elosua
  • Sek Kathiresan
  • Gavin Lucas
  • Olle Melander
  • Christopher J. O'Donnell
  • Veikko Salomaa
  • Stephen M. Schwartz
  • Benjamin F. Voight
  • Brenda W. Penninx
  • Johannes H. Smit
  • Nicole Vogelzangs
  • Dorret I. Boomsma
  • Eco J. C. de Geus
  • Jacqueline M. Vink
  • Gonneke Willemsen
  • Stephen J. Chanock
  • Fangyi Gu
  • Susan E. Hankinson
  • David J. Hunter
  • Albert Hofman
  • Henning Tiemeier
  • Andre G. Uitterlinden
  • Cornelia M. van Duijn
  • Stefan Walter
  • Daniel I. Chasman
  • Brendan M. Everett
  • Guillaume Pare
  • Paul M. Ridker
  • Ming D. Li
  • Hermine H. Maes
  • Janet Audrain-McGovern
  • Danielle Posthuma
  • Laura M. Thornton
  • Caryn Lerman
  • Jaakko Kaprio
  • Jed E. Rose
  • John P. A. Ioannidis
  • Peter Kraft
  • Dan-Yu Lin
  • Patrick F. Sullivan

Summary, in English

Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2010

Language

English

Pages

134-441

Publication/Series

Nature Genetics

Volume

42

Issue

5

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cardiac and Cardiovascular Systems
  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718