Meta-analysis and imputation refines the association of 15q25 with smoking quantity

Jason Z. Liu; Federica Tozzi; Dawn M. Waterworth; Sreekumar G. Pillai; Pierandrea Muglia; Lefkos Middleton; Wade Berrettini; Christopher W. Knouff; Xin Yuan; Gerard Waeber; Peter Vollenweider; Martin Preisig; Nicholas J. Wareham; Jing Hua Zhao; Ruth J. F. Loos; Ines Barroso; Kay-Tee Khaw; Scott Grundy; Philip Barter; Robert Mahley; Antero Kesaniemi; Ruth McPherson; John B. Vincent; John Strauss; James L. Kennedy; Anne Farmer; Peter McGuffin; Richard Day; Keith Matthews; Per Bakke; Amund Gulsvik; Susanne Lucae; Marcus Ising; Tanja Brueckl; Sonja Horstmann; H-Erich Wichmann; Rajesh Rawal; Norbert Dahmen; Claudia Lamina; Ozren Polasek; Lina Zgaga; Jennifer Huffman; Susan Campbell; Jaspal Kooner; John C. Chambers; Mary Susan Burnett; Joseph M. Devaney; Augusto D. Pichard; Kenneth M. Kent; Lowell Satler; Joseph M. Lindsay; Ron Waksman; Stephen Epstein; James F. Wilson; Sarah H. Wild; Harry Campbell; Veronique Vitart; Muredach P. Reilly; Mingyao Li; Liming Qu; Robert Wilensky; William Matthai; Hakon H. Hakonarson; Daniel J. Rader; Andre Franke; Michael Wittig; Arne Schaefer; Manuela Uda; Antonio Terracciano; Xiangjun Xiao; Fabio Busonero; Paul Scheet; David Schlessinger; David St Clair; Dan Rujescu; Goncalo R. Abecasis; Hans Joergen Grabe; Alexander Teumer; Henry Voelzke; Astrid Petersmann; Ulrich John; Igor Rudan; Caroline Hayward; Alan F. Wright; Ivana Kolcic; Benjamin J. Wright; John R. Thompson; Anthony J. Balmforth; Alistair S. Hall; Nilesh J. Samani; Carl A. Anderson; Tariq Ahmad; Christopher G. Mathew; Miles Parkes; Jack Satsangi; Mark Caulfield; Patricia B. Munroe; Martin Farrall; Anna Dominiczak; Jane Worthington; Wendy Thomson; Steve Eyre; Anne Barton; Vincent Mooser; Clyde Francks; Jonathan Marchini; Wellcome Trust Case Control Consor

doi:10.1038/ng.572

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Meta-analysis and imputation refines the association of 15q25 with smoking quantity

Journal article

Peer reviewed

Meta-analysis and imputation refines the association of 15q25 with smoking quantity

Jason Z. Liu, Federica Tozzi, Dawn M. Waterworth, Sreekumar G. Pillai, Pierandrea Muglia, Lefkos Middleton, Wade Berrettini, Christopher W. Knouff, Xin Yuan, Gerard Waeber, …

Nature genetics, Vol.42(5), pp.436-U75

01/05/2010

DOI: https://doi.org/10.1038/ng.572

PMCID: PMC3612983

PMID: 20418889

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Smoking is a leading global cause of disease and mortality(1). We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

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Title: Meta-analysis and imputation refines the association of 15q25 with smoking quantity
Creators - without role: Jason Z. Liu - University of Oxford
Federica Tozzi - GlaxoSmithKline
Dawn M. Waterworth - GlaxoSmithKline
Sreekumar G. Pillai - GlaxoSmithKline
Pierandrea Muglia - GlaxoSmithKline
Lefkos Middleton - Imperial College London
Wade Berrettini - University of Pennsylvania
Christopher W. Knouff - Research Triangle Park Foundation
Xin Yuan - GlaxoSmithKline
Gerard Waeber - University of Lausanne
Peter Vollenweider - University of Lausanne
Martin Preisig - University of Lausanne
Nicholas J. Wareham - Medical Research Council
Jing Hua Zhao - Medical Research Council
Ruth J. F. Loos - Medical Research Council
Ines Barroso - Wellcome Sanger Institute
Kay-Tee Khaw - University of Cambridge
Scott Grundy - The University of Texas Southwestern Medical Center
Philip Barter - The Heart Research Institute
Robert Mahley - Gladstone Institutes
Antero Kesaniemi - University of Oulu
Ruth McPherson - University of Ottawa
John B. Vincent - Centre for Addiction and Mental Health
John Strauss - Centre for Addiction and Mental Health
James L. Kennedy - Centre for Addiction and Mental Health
Anne Farmer - King's College London
Peter McGuffin - King's College London
Richard Day - University of Dundee
Keith Matthews - University of Dundee
Per Bakke - University of Bergen
Amund Gulsvik - University of Bergen
Susanne Lucae - Max Planck Institute of Psychiatry
Marcus Ising - Max Planck Institute of Psychiatry
Tanja Brueckl - Max Planck Institute of Psychiatry
Sonja Horstmann - Max Planck Institute of Psychiatry
H-Erich Wichmann - Helmholtz Zentrum München
Rajesh Rawal - Helmholtz Zentrum München
Norbert Dahmen - Psychiatrische Klinik und Poliklinik University of Mainz, Mainz, Germany
Claudia Lamina - Helmholtz Zentrum München
Ozren Polasek - University of Zagreb
Lina Zgaga - University of Edinburgh
Jennifer Huffman - MRC Institute of Genetics and Molecular Medicine
Susan Campbell - MRC Institute of Genetics and Molecular Medicine
Jaspal Kooner - Imperial College London
John C. Chambers - Imperial College London
Mary Susan Burnett - MedStar Washington Hospital Center
Joseph M. Devaney - MedStar Washington Hospital Center
Augusto D. Pichard - MedStar Washington Hospital Center
Kenneth M. Kent - MedStar Washington Hospital Center
Lowell Satler - MedStar Washington Hospital Center
Joseph M. Lindsay - MedStar Washington Hospital Center
Ron Waksman - MedStar Washington Hospital Center
Stephen Epstein - MedStar Washington Hospital Center
James F. Wilson - University of Edinburgh
Sarah H. Wild - University of Edinburgh
Harry Campbell - University of Edinburgh
Veronique Vitart - MRC Institute of Genetics and Molecular Medicine
Muredach P. Reilly - Cardiovascular Institute of the South
Mingyao Li - University of Pennsylvania
Liming Qu - University of Pennsylvania
Robert Wilensky - Cardiovascular Institute of the South
William Matthai - Cardiovascular Institute of the South
Hakon H. Hakonarson - Children's Hospital of Philadelphia
Daniel J. Rader - Cardiovascular Institute of the South
Andre Franke - Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
Michael Wittig - Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
Arne Schaefer - Univ Kiel, Inst Clin Mol Biol, Kiel, Germany
Manuela Uda - Institute of Genetic and Biomedical Research
Antonio Terracciano - National Institute on Aging
Xiangjun Xiao - The University of Texas MD Anderson Cancer Center
Fabio Busonero - Institute of Genetic and Biomedical Research
Paul Scheet - The University of Texas MD Anderson Cancer Center
David Schlessinger - National Institute on Aging
David St Clair - University of Aberdeen
Dan Rujescu - Ludwig-Maximilians-Universität München
Goncalo R. Abecasis - Statistical Research
Hans Joergen Grabe - University of Greifswald
Alexander Teumer - University of Greifswald
Henry Voelzke - University of Greifswald
Astrid Petersmann - Greifswald University Hospital
Ulrich John - University of Greifswald
Igor Rudan - University of Split
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Alan F. Wright - MRC Institute of Genetics and Molecular Medicine
Ivana Kolcic - University of Zagreb
Benjamin J. Wright - University of Leicester
John R. Thompson - University of Leicester
Anthony J. Balmforth - University of Leeds
Alistair S. Hall - University of Leeds
Nilesh J. Samani - University of Leicester
Carl A. Anderson - Wellcome Sanger Institute
Tariq Ahmad - Peninsula College of Medicine and Dentistry
Christopher G. Mathew - King's College London
Miles Parkes - Addenbrooke's Hospital
Jack Satsangi - University of Edinburgh
Mark Caulfield - Queen Mary University of London
Patricia B. Munroe - Queen Mary University of London
Martin Farrall - University of Oxford
Anna Dominiczak - British Heart Foundation
Jane Worthington - University of Manchester
Wendy Thomson - University of Manchester
Steve Eyre - University of Manchester
Anne Barton - University of Manchester
Vincent Mooser - GlaxoSmithKline
Clyde Francks - GlaxoSmithKline, Div Genet, Verona, Italy
Jonathan Marchini - University of Oxford
Wellcome Trust Case Control Consor
Publication Details: Nature genetics, Vol.42(5), pp.436-U75
Publisher: NATURE PORTFOLIO
Number of pages: 7
Grant note: GSK; GlaxoSmithKline G0800675 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission Oxford University CZB/4/710 / Chief Scientist Office ZIAAG000183 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) G0701863 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) R01DA025201 / 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
Identifiers: 9926004108331
Academic Unit: Prince Sattam Bin Abdulaziz University
Language: English
Resource Type: Journal article