Evidence map›Paper›PMID 26423011›Full record

ArticleThe Lancet. Respiratory medicine2015

Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank.

Louise V Wain, Nick Shrine, Suzanne Miller, Victoria E Jackson, Ioanna Ntalla, María Soler Artigas, Charlotte K Billington, Abdul Kader Kheirallah, Richard Allen, James P Cook and 31 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Respiratory medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 252 papers, 23 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
252citing papers in PubMed, 23 pooled it
40.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

252 citing papers in PubMed, 23 syntheses or guidelines pooled it, 433 citations in OpenAlex.

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192 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

41 authors at 18 institutions in 9 countries.

Louise V WainDepartment of Health Sciences, University of Leicester, Leicester, UK.
Nick ShrineDepartment of Health Sciences, University of Leicester, Leicester, UK.
Suzanne MillerDivision of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Victoria E JacksonDepartment of Health Sciences, University of Leicester, Leicester, UK.
Ioanna NtallaDepartment of Health Sciences, University of Leicester, Leicester, UK.
María Soler ArtigasDepartment of Health Sciences, University of Leicester, Leicester, UK.
Charlotte K BillingtonDivision of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Abdul Kader KheirallahDivision of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Richard AllenDepartment of Health Sciences, University of Leicester, Leicester, UK.
James P CookDepartment of Health Sciences, University of Leicester, Leicester, UK.
Kelly ProbertDivision of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Ma'en ObeidatUniversity of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
Yohan BosséInstitut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec, QC, Canada.
Ke HaoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Dirkje S PostmaDepartment of Pulmonary Medicine and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Peter D ParéUniversity of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
Adaikalavan RamasamyDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Department of Medical and Molecular Genetics, King's College London, London, UK; Jenner Institute, University of Oxford, Oxford, UK.
UK Brain Expression Consortium (UKBEC)
Reedik MägiEstonian Genome Center, University of Tartu, Tartu, Estonia.
Evelin MihailovEstonian Genome Center, University of Tartu, Tartu, Estonia.
Eva ReinmaaEstonian Genome Center, University of Tartu, Tartu, Estonia.
Erik MelénInstitute of Environmental Medicine, Karolinska Institutet and Sachs' Children's Hospital, Stockholm, Sweden.
Jared O'ConnellDepartment of Statistics, University of Oxford, Oxford, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Eleni FrangouDepartment of Statistics, University of Oxford, Oxford, UK; Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Olivier DelaneauDepartment of Statistics, University of Oxford, Oxford, UK; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
OxGSK Consortium
Colin FreemanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Desislava PetkovaWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Mark McCarthyWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Ian SayersDivision of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Panos DeloukasWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
Richard HubbardFaculty of Medicine and Health Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
Ian PavordRespiratory Medicine, University of Oxford, Oxford, UK.
Anna L HansellUK Small Area Health Statistics Unit, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK; Imperial College Healthcare NHS Trust, St Mary's Hospital, Paddington, London, UK.
Neil C ThomsonInstitute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Eleftheria ZegginiWellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
Andrew P MorrisDepartment of Biostatistics, University of Liverpool, Liverpool, UK.
Jonathan MarchiniDepartment of Statistics, University of Oxford, Oxford, UK; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
David P StrachanPopulation Health Research Institute, St George's, University of London, London, UK.
Martin D TobinDepartment of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, UK. Electronic address: mt47@leicester.ac.uk.
Ian P HallDivision of Respiratory Medicine, Queen's Medical Centre, University of Nottingham, Nottingham, UK. Electronic address: ian.hall@nottingham.ac.uk.
University of Leicester · GBUniversity of Oxford · GBUniversity of Nottingham · GBQueen's Medical Centre · GBUniversity of Tartu · EECentre for Human Genetics · GBSt. Paul's Hospital · CAOxford Centre for Diabetes, Endocrinology and Metabolism · GBQueen Mary University of London · GBSachs' Children and Youth Hospital · SESt George's, University of London · GBSt Mary's Hospital · GBTongji University · CNUniversité Laval · CAUniversity of Glasgow · GBUniversity of Groningen · NLUniversity of Liverpool · GBWellcome Sanger Institute · GB

Funding

Aging-related Traits and Disease Risk Factors in a Sardinian Population CohortZIAAG000675 · NIA · NATIONAL INSTITUTE ON AGING · PI GOROSPE, MYRIAM · 2009 to 2021
$5.7M
Chief Scientist Office CZB/4/540Chief Scientist Office ETM/137Chief Scientist Office ETM/75European Research Council 617306Medical Research Council G0501942Medical Research Council G0600329Medical Research Council G0800675Medical Research Council G0800759Medical Research Council G0801056Medical Research Council G0902313Medical Research Council G1000861Medical Research Council MC_PC_12010Medical Research Council MC_QA137853Medical Research Council MR/L01341X/1Wellcome Trust 093707Wellcome Trust 098017Wellcome Trust WT091310
6 · The paper itself

Abstract

backgroundUnderstanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.

methodsWe sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers. We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population. We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1. We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease. We set genome-wide significance at p<5 × 10(-8).

findingsUK Biobank participants were recruited from March 15, 2006, to July 7, 2010. Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012. We selected 50,008 unique samples: 10,002 individuals with low FEV1, 10,000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups. We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2.29 × 10(-16)) and between individuals with and without doctor-diagnosed asthma (p=6.06 × 10(-11)). We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2). These variants also showed association with COPD, including in individuals with no history of smoking. The number of copies of a 150 kb region containing the 5' end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1. We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.

interpretationBy sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour. These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.

fundingMedical Research Council.

Indexed as

AdolescentAdultAgedAged, 80 and overBiological Specimen BanksCase-Control StudiesFemaleForced Expiratory VolumeGenetic Association StudiesHumansLungMaleMiddle AgedPolymorphism, Single NucleotidePulmonary Disease, Chronic ObstructiveRisk Factors

Identifiers

PMID26423011
PMCPMC4593935
OpenAlexW2149200222

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.