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

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; Tobacco and Genetics Consortium

doi:10.1038/ng.571

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

Journal article

Peer reviewed

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

Helena Furberg, YunJung Kim, Jennifer Dackor, Eric Boerwinkle, Nora Franceschini, Diego Ardissino, Luisa Bernardinelli, Pier M. Mannucci, Francesco Mauri, Piera A. Merlini, …

Nature genetics, Vol.42(5), pp.441-U134

01/05/2010

DOI: https://doi.org/10.1038/ng.571

PMCID: PMC2914600

PMID: 20418890

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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.

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Title: Genome-wide meta-analyses identify multiple loci associated with smoking behavior
Creators - without role: Helena Furberg - Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
YunJung Kim - Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
Jennifer Dackor - Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
Eric Boerwinkle - Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA
Nora Franceschini - Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA
Diego Ardissino - University of Parma
Luisa Bernardinelli - University of Cambridge
Pier M. Mannucci - University of Milan
Francesco Mauri - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Piera A. Merlini - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Devin Absher - HudsonAlpha Inst Biotechnol, Huntsville, AL USA
Themistocles L. Assimes - Stanford University
Stephen P. Fortmann - Stanford University
Carlos Iribarren - Kaiser Permanente
Joshua W. Knowles - Stanford University
Thomas Quertermous - Stanford University
Luigi Ferrucci
Toshiko Tanaka - NIA, Medstart Res Inst, Baltimore, MD 21224 USA
Joshua C. Bis - University of Washington
Curt D. Furberg - Wake Forest University
Talin Haritunians - College Station Medical Center
Barbara McKnight - University of Washington
Bruce M. Psaty - University of Washington
Kent D. Taylor - College Station Medical Center
Evan L. Thacker - University of Washington
Peter Almgren - Lund University
Leif Groop - Lund University
Claes Ladenvall - Lund University
Michael Boehnke - Biostat
Anne U. Jackson - Biostat
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
Heather M. Stringham - Biostat
Jaakko Tuomilehto - University of Helsinki
Emelia J. Benjamin - Boston University
Shih-Jen Hwang - NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA
Daniel Levy - Boston University
Sarah Rosner Preis - NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA
Ramachandran S. Vasan - Boston University
Jubao Duan - NorthShore Univ, Ctr Psychiat Genet, HealthSyst Res Inst, Evanston, IL USA
Pablo V. Gejman - NorthShore Univ, Ctr Psychiat Genet, HealthSyst Res Inst, Evanston, IL USA
Douglas F. Levinson - Stanford University
Alan R. Sanders - NorthShore Univ, Ctr Psychiat Genet, HealthSyst Res Inst, Evanston, IL USA
Jianxin Shi - Biostat
Esther H. Lips - IARC, Lyon, France
James D. Mckay - IARC, Lyon, France
Antonio Agudo - Inst Catala Oncol, Barcelona, Spain
Luigi Barzan - Gen Hosp, Pordenone, Italy
Vladimir Bencko - Charles University
Simone Benhamou - Inserm
Xavier Castellsague - Inst Catala Oncol, Barcelona, Spain
Cristina Canova - University of Padua
David I. Conway - University of Glasgow
Eleonora Fabianova - Specialized Inst Hyg & Epidemiol, Banska Bystrica, Slovakia
Lenka Foretova - Mécanique et Engrenage Moderne
Vladimir Janout - Palacky Univ, CR-77147 Olomouc, Czech Republic
Claire M. Healy - Supreme Council Of Health
Ivana Holcatova - Charles University
Kristina Kjaerheim - Canc Registry Norway, Oslo, Norway
Pagona Lagiou - National and Kapodistrian University of Athens
Jolanta Lissowska - Maria Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland
Ray Lowry - Supreme Council Of Health
Tatiana V. Macfarlane - University of Aberdeen
Dana Mates - Inst Publ Hlth, Bucharest, Romania
Lorenzo Richiardi - University of Turin
Peter Rudnai - Natl Inst Environm Hlth, Budapest, Hungary
Neonilia Szeszenia-Dabrowska - College Station Medical Center
David Zaridze - Inst Carcinogenesis Canc Res Ctr, Moscow, Russia
Ariana Znaor - Croatian Natl Canc Registry, Zagreb, Croatia
Mark Lathrop - Evry
Paul Brennan - IARC, Lyon, France
Stefania Bandinelli - Florence
Timothy M. Frayling - University of Exeter
Jack M. Guralnik - NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA
Yuri Milaneschi - Florence
John R. B. Perry - University of Exeter
David Altshuler - Broad Institute
Roberto Elosua - College Station Medical Center
Sek Kathiresan - Broad Institute
Gavin Lucas - College Station Medical Center
Olle Melander - Malmö University
Christopher J. O'Donnell - Framingham Heart Study
Veikko Salomaa - Natl Inst Hlth & Welf THL, Helsinki, Finland
Stephen M. Schwartz - University of Washington
Benjamin F. Voight - Broad Institute
Brenda W. Penninx - College Station Medical Center
Johannes H. Smit - College Station Medical Center
Nicole Vogelzangs - College Station Medical Center
Dorret I. Boomsma - University of Amsterdam
Eco J. C. de Geus - University of Amsterdam
Jacqueline M. Vink - University of Amsterdam
Gonneke Willemsen - University of Amsterdam
Stephen J. Chanock - NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
Fangyi Gu - Harvard University
Susan E. Hankinson - Brigham and Women's Hospital
David J. Hunter - Harvard University
Albert Hofman - Erasmus MC
Henning Tiemeier - Erasmus MC
Andre G. Uitterlinden - Erasmus MC
Cornelia M. van Duijn - Erasmus MC
Stefan Walter - Erasmus MC
Daniel I. Chasman - Harvard University
Brendan M. Everett - Harvard University
Guillaume Pare - Harvard University
Paul M. Ridker - Harvard University
Ming D. Li - University of Virginia
Hermine H. Maes - Virginia Commonwealth University
Janet Audrain-McGovern - Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA
Danielle Posthuma - University of Amsterdam
Laura M. Thornton - Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA
Caryn Lerman - Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA
Jaakko Kaprio - University of Helsinki
Jed E. Rose - Duke University
John P. A. Ioannidis - Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
Peter Kraft - Harvard University
Dan-Yu Lin - Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA
Patrick F. Sullivan - Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA
Tobacco and Genetics Consortium
Publication Details: Nature genetics, Vol.42(5), pp.441-U134
Publisher: Springer Nature
Number of pages: 9
Grant note: U01HL054527 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01DA012844 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission K07CA118412 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) University of North Carolina Lineberger Comprehensive Cancer Center University K07 CA118412 / US National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01DK072193 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) NWO 480-05-003 / Netherlands Scientific Organization
Identifiers: 9936569708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article