Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

A Mesut Erzurumluoglu; Mengzhen Liu; Victoria E Jackson; Daniel R Barnes; Gargi Datta; Carl A Melbourne; Robin Young; Chiara Batini; Praveen Surendran; Tao Jiang; Sheikh Daud Adnan; Saima Afaq; Arpana Agrawal; Elisabeth Altmaier; Antonis C Antoniou; Folkert W Asselbergs; Clemens Baumbach; Laura Bierut; Sarah Bertelsen; Michael Boehnke; Michiel L Bots; David M Brazel; John C Chambers; Jenny Chang-Claude; Chu Chen; Janie Corley; Yi-Ling Chou; Sean P David; Rudolf A de Boer; Christiaan A de Leeuw; Joe G Dennis; Anna F Dominiczak; Alison M Dunning; Douglas F Easton; Charles Eaton; Paul Elliott; Evangelos Evangelou; Jessica D Faul; Tatiana Foroud; Alison Goate; Jian Gong; Hans J Grabe; Jeff Haessler; Christopher Haiman; Göran Hallmans; Anke R Hammerschlag; Sarah E Harris; Andrew Hattersley; Andrew Heath; Chris Hsu; William G Iacono; Stavroula Kanoni; Manav Kapoor; Jaakko Kaprio; Sharon L Kardia; Fredrik Karpe; Jukka Kontto; Jaspal S Kooner; Charles Kooperberg; Kari Kuulasmaa; Markku Laakso; Dongbing Lai; Claudia Langenberg; Nhung Le; Guillaume Lettre; Anu Loukola; Jian'an Luan; Pamela A F Madden; Massimo Mangino; Riccardo E Marioni; Eirini Marouli; Jonathan Marten; Nicholas G Martin; Matt McGue; Kyriaki Michailidou; Evelin Mihailov; Alireza Moayyeri; Marie Moitry; Martina Müller-Nurasyid; Aliya Naheed; Matthias Nauck; Matthew J Neville; Sune Fallgaard Nielsen; Kari North; Markus Perola; Paul D P Pharoah; Giorgio Pistis; Tinca J Polderman; Danielle Posthuma; Neil Poulter; Beenish Qaiser; Asif Rasheed; Alex Reiner; Frida Renström; John Rice; Rebecca Rohde; Olov Rolandsson; Nilesh J Samani; Maria Samuel; David Schlessinger; Steven H Scholte; Robert A Scott; Peter Sever; Yaming Shao; Nick Shrine; Jennifer A Smith; John M Starr; Kathleen Stirrups; Danielle Stram; Heather M Stringham; Ioanna Tachmazidou; Jean-Claude Tardif; Deborah J Thompson; Hilary A Tindle; Vinicius Tragante; Stella Trompet; Valerie Turcot; Jessica Tyrrell; Ilonca Vaartjes; Andries R van der Leij; Peter van der Meer; Tibor V Varga; Niek Verweij; Henry Völzke; Nicholas J Wareham; Helen R Warren; David R Weir; Stefan Weiss; Leah Wetherill; Hanieh Yaghootkar; Ersin Yavas; Yu Jiang; Fang Chen; Xiaowei Zhan; Weihua Zhang; Wei Zhao; Kaixin Zhou; Philippe Amouyel; Stefan Blankenberg; Mark J Caulfield; Rajiv Chowdhury; Francesco Cucca; Ian J Deary; Panos Deloukas; Emanuele Di Angelantonio; Marco Ferrario; Jean Ferrières; Paul W Franks; Tim M Frayling; Philippe Frossard; Ian P Hall; Caroline Hayward; Jan-Håkan Jansson; J Wouter Jukema; Frank Kee; Satu Männistö; Andres Metspalu; Patricia B Munroe; Børge Grønne Nordestgaard; Colin N A Palmer; Veikko Salomaa; Naveed Sattar; Timothy Spector; David Peter Strachan; Pim van der Harst; Eleftheria Zeggini; Danish Saleheen; Adam S Butterworth; Louise V Wain; Goncalo R Abecasis; John Danesh; Martin D Tobin; Scott Vrieze; Dajiang J Liu; Joanna M M Howson; Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ consortium

doi:10.1038/s41380-018-0313-0

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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Journal article

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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

A Mesut Erzurumluoglu, Mengzhen Liu, Victoria E Jackson, Daniel R Barnes, Gargi Datta, Carl A Melbourne, Robin Young, Chiara Batini, Praveen Surendran, Tao Jiang, …

Molecular psychiatry, Vol.25(10), pp.2392-2409

01/10/2020

DOI: https://doi.org/10.1038/s41380-018-0313-0

PMID: 30617275

Abstract

Biological Specimen Banks

Databases, Factual

Europe - ethnology

Exome

Female

Genetic Loci

Humans

Male

Polymorphism, Single Nucleotide - genetics

Smoking - genetics

United Kingdom

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10 ) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10 ) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

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Title: Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
Creators - without role: A Mesut Erzurumluoglu - University of Leicester
Mengzhen Liu - University of Minnesota
Victoria E Jackson - University of Leicester
Daniel R Barnes - University of Cambridge
Gargi Datta - University of Minnesota
Carl A Melbourne - University of Leicester
Robin Young - University of Cambridge
Chiara Batini - University of Leicester
Praveen Surendran - University of Cambridge
Tao Jiang - University of Cambridge
Sheikh Daud Adnan - National Institute of Cardiovascular Diseases
Saima Afaq - Imperial College London
Arpana Agrawal - Washington University in St. Louis
Elisabeth Altmaier - Helmholtz Zentrum München
Antonis C Antoniou - University of Cambridge
Folkert W Asselbergs - UCL Australia
Clemens Baumbach - Helmholtz Zentrum München
Laura Bierut - Washington University in St. Louis
Sarah Bertelsen - Icahn School of Medicine at Mount Sinai
Michael Boehnke - University of Michigan–Ann Arbor
Michiel L Bots - University Medical Center Utrecht
David M Brazel - University of Colorado Boulder
John C Chambers - Nanyang Technological University
Jenny Chang-Claude - German Cancer Research Center
Chu Chen - Fred Hutch Cancer Center
Janie Corley - University of Edinburgh
Yi-Ling Chou - Washington University in St. Louis
Sean P David - Stanford University
Rudolf A de Boer - University Medical Center Groningen
Christiaan A de Leeuw - Amsterdam Neuroscience
Joe G Dennis - University of Cambridge
Anna F Dominiczak - University of Glasgow
Alison M Dunning - University of Cambridge
Douglas F Easton - University of Cambridge
Charles Eaton - University of Washington
Paul Elliott - Imperial College London
Evangelos Evangelou - University of Ioannina
Jessica D Faul - University of Michigan–Ann Arbor
Tatiana Foroud - Indiana University
Alison Goate - Icahn School of Medicine at Mount Sinai
Jian Gong - Fred Hutch Cancer Center
Hans J Grabe - Greifswald University Hospital
Jeff Haessler - Fred Hutch Cancer Center
Christopher Haiman - University of Southern California
Göran Hallmans - Umeå University
Anke R Hammerschlag - Amsterdam Neuroscience
Sarah E Harris - University of Edinburgh
Andrew Hattersley - University of Exeter
Andrew Heath - Washington University in St. Louis
Chris Hsu - University of Southern California
William G Iacono - University of Minnesota
Stavroula Kanoni - Queen Mary University of London
Manav Kapoor - Icahn School of Medicine at Mount Sinai
Jaakko Kaprio - University of Helsinki
Sharon L Kardia - University of Michigan–Ann Arbor
Fredrik Karpe - University of Oxford
Jukka Kontto - Finnish Institute for Health and Welfare
Jaspal S Kooner - Imperial College London
Charles Kooperberg - Fred Hutch Cancer Center
Kari Kuulasmaa - Finnish Institute for Health and Welfare
Markku Laakso - Finland University
Dongbing Lai - Indiana University
Claudia Langenberg - University of Cambridge
Nhung Le - Southern Illinois University School of Medicine
Guillaume Lettre - Université de Montréal
Anu Loukola - University of Helsinki
Jian'an Luan - University of Cambridge
Pamela A F Madden - Washington University in St. Louis
Massimo Mangino - Guy's and St Thomas' NHS Foundation Trust
Riccardo E Marioni - University of Edinburgh
Eirini Marouli - Queen Mary University of London
Jonathan Marten - University of Edinburgh
Nicholas G Martin - QIMR Berghofer Medical Research Institute
Matt McGue - University of Minnesota
Kyriaki Michailidou - University of Cambridge
Evelin Mihailov - University of Tartu
Alireza Moayyeri - University College London
Marie Moitry - University of Strasbourg
Martina Müller-Nurasyid - Helmholtz Zentrum München
Aliya Naheed - International Centre for Diarrhoeal Disease Research
Matthias Nauck - Greifswald University Hospital
Matthew J Neville - University of Oxford
Sune Fallgaard Nielsen - Copenhagen University Hospital
Kari North - University of North Carolina at Chapel Hill
Markus Perola - University of Helsinki
Paul D P Pharoah - University of Cambridge
Giorgio Pistis - Institute of Genetic and Biomedical Research
Tinca J Polderman - Amsterdam Neuroscience
Danielle Posthuma - Amsterdam Neuroscience
Neil Poulter - Imperial College London
Beenish Qaiser - Institute for Molecular Medicine Finland
Asif Rasheed - Center for Non-Communicable Diseases
Alex Reiner - University of Washington
Frida Renström - Skåne University Hospital
John Rice - Washington University in St. Louis
Rebecca Rohde - University of North Carolina at Chapel Hill
Olov Rolandsson - Umeå University
Nilesh J Samani - University of Leicester
Maria Samuel - Center for Non-Communicable Diseases
David Schlessinger - National Institute on Aging
Steven H Scholte - University of Amsterdam
Robert A Scott - University of Cambridge
Peter Sever - Imperial College London
Yaming Shao - University of North Carolina, Chapel Hill, NC, USA
Nick Shrine - University of Leicester
Jennifer A Smith - University of Michigan–Ann Arbor
John M Starr - University of Edinburgh
Kathleen Stirrups - University of Cambridge
Danielle Stram - Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Heather M Stringham - University of Michigan–Ann Arbor
Ioanna Tachmazidou - Wellcome Sanger Institute
Jean-Claude Tardif - Université de Montréal
Deborah J Thompson - University of Cambridge
Hilary A Tindle - Vanderbilt University
Vinicius Tragante - University Medical Center Utrecht
Stella Trompet - Leiden University Medical Center
Valerie Turcot - Montreal Heart Institute
Jessica Tyrrell - University of Exeter
Ilonca Vaartjes - University Medical Center Utrecht
Andries R van der Leij - University of Amsterdam
Peter van der Meer - University Medical Center Groningen
Tibor V Varga - Skåne University Hospital
Niek Verweij - Broad Institute
Henry Völzke - Institute for Community Medicine, University Medicine Greifswald, 17475, Greifswald, Germany
Nicholas J Wareham - University of Cambridge
Helen R Warren - Queen Mary University of London
David R Weir - University of Michigan–Ann Arbor
Stefan Weiss - University of Greifswald
Leah Wetherill - Indiana University
Hanieh Yaghootkar - University of Exeter
Ersin Yavas - Pennsylvania State University
Yu Jiang - Pennsylvania State University
Fang Chen - Pennsylvania State University
Xiaowei Zhan - Department of Clinical Science, Center for Genetics of Host Defense, University of Texas Southwestern, Dallas, TX, USA
Weihua Zhang - London North West Healthcare NHS Trust
Wei Zhao - University of Pennsylvania
Wei Zhao - University of Michigan–Ann Arbor
Kaixin Zhou - University of Dundee
Philippe Amouyel - Institut Pasteur
Stefan Blankenberg - University Medical Center Hamburg-Eppendorf
Mark J Caulfield - Queen Mary University of London
Rajiv Chowdhury - University of Cambridge
Francesco Cucca - GeneTiCA
Ian J Deary - University of Edinburgh
Panos Deloukas - King Abdulaziz University
Emanuele Di Angelantonio - University of Cambridge
Marco Ferrario - University of Insubria
Jean Ferrières - Inserm
Paul W Franks - Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA
Tim M Frayling - University of Exeter
Philippe Frossard - Centre for Non-Communicable Diseases, Karachi, Pakistan
Ian P Hall - University of Nottingham
Caroline Hayward - University of Edinburgh
Jan-Håkan Jansson - Umeå University
J Wouter Jukema - The Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
Frank Kee - Queens University
Satu Männistö - Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271, Helsinki, Finland
Andres Metspalu - University of Tartu
Patricia B Munroe - Queen Mary University of London
Børge Grønne Nordestgaard - Copenhagen University Hospital
Colin N A Palmer - University of Dundee
Veikko Salomaa - Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271, Helsinki, Finland
Naveed Sattar - University of Glasgow
Timothy Spector - Department of Twin Research and Genetic Epidemiology, Kings College London, London, SE1 7EH, UK
David Peter Strachan - University of London
Pim van der Harst - University Medical Center Groningen
Eleftheria Zeggini - Wellcome Sanger Institute
Danish Saleheen - Center for Non-Communicable Diseases
Adam S Butterworth - University of Cambridge
Louise V Wain - Glenfield Hospital
Goncalo R Abecasis - University of Michigan–Ann Arbor
John Danesh - University of Cambridge
Martin D Tobin - Glenfield Hospital
Scott Vrieze - University of Minnesota
Dajiang J Liu - Pennsylvania State University
Joanna M M Howson - University of Cambridge
Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ consortium
Publication Details: Molecular psychiatry, Vol.25(10), pp.2392-2409
Grant note: MR/M013111/1 / Medical Research Council SP/04/002 / British Heart Foundation R01 DK062370 / NIDDK NIH HHS MR/L01632X/1 / Medical Research Council 16/136/68 / Department of Health 10119 / Cancer Research UK MC_PC_12010 / Medical Research Council G0800270 / Medical Research Council MC_QA137853 / Medical Research Council R01 HL119443 / NHLBI NIH HHS 090532 / Wellcome Trust MR/N01104X/2 / Medical Research Council R01 HG008983 / NHGRI NIH HHS MR/L01341X/1 / Medical Research Council WT098051 / Wellcome Trust MR/S003746/1 / Medical Research Council G0601966 / Medical Research Council U01 AG009740 / NIA NIH HHS MC_UU_12015/1 / Medical Research Council SP/08/005/25115 / British Heart Foundation MR/N01104X/1 / Medical Research Council HPRU-2012-10141 / Department of Health ETM/55 / Chief Scientist Office C490/A16561 / Cancer Research UK R01 GM126479 / NIGMS NIH HHS MR/K023241/1 / Medical Research Council PG/02/128 / British Heart Foundation MR/S003762/1 / Medical Research Council 104036/Z/14/Z / Wellcome Trust MC_PC_17228 / Medical Research Council RE/13/5/30177 / British Heart Foundation 085475 / Wellcome Trust G0700931 / Medical Research Council 268834 / European Research Council RC2 AG036495 / NIA NIH HHS G9521010D / Medical Research Council MR/R023484/1 / Medical Research Council RG/07/005/23633 / British Heart Foundation 10124 / Cancer Research UK MC_U106179471 / Medical Research Council 084723/Z/08/Z / Wellcome Trust RG/08/014/24067 / British Heart Foundation SP/09/002 / British Heart Foundation RP-PG-0407-10371 / Department of Health MC_UU_00007/10 / Medical Research Council RC4 AG039029 / NIA NIH HHS 083948 / Wellcome Trust RG/13/13/30194 / British Heart Foundation MR/N011317/1 / Medical Research Council MR/L003120/1 / Medical Research Council U01 DK062370 / NIDDK NIH HHS BTRU-2014-10024 / Department of Health G1001799 / Medical Research Council 098381 / Wellcome Trust R21 DA040177 / NIDA NIH HHS CZD/16/6 / Chief Scientist Office MR/K026992/1 / Medical Research Council G1000861 / Medical Research Council R01 HD057194 / NICHD NIH HHS BB/F019394/1 / Biotechnology and Biological Sciences Research Council RG/14/5/30893 / British Heart Foundation
Identifiers: 9938022208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article