Evidence map›Paper›PMID 29066090›Full record

ArticleThe Lancet. Respiratory medicine2017

Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study.

Richard J Allen, Joanne Porte, Rebecca Braybrooke, Carlos Flores, Tasha E Fingerlin, Justin M Oldham, Beatriz Guillen-Guio, Shwu-Fan Ma, Tsukasa Okamoto, Alison E John and 33 more

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

Article in The Lancet. Respiratory medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
177citing papers in PubMed, 9 pooled it
22.3field-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

177 citing papers in PubMed, 9 syntheses or guidelines pooled it, 296 citations in OpenAlex.

  1. Pooled it
  2. Common single nucleotide polymorphisms associated with idiopathic pulmonary fibrosis: a systematic review.European respiratory review : an official journal of the European Respiratory Society · 2024
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  17. Sex Differences in Lung Immunity.Immunological reviews · 2026
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117 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors at 20 institutions in 5 countries.

Richard J AllenDepartment of Health Sciences, University of Leicester, Leicester, UK.
Joanne PorteDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK; Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK.
Rebecca BraybrookeNational Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK; Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
Carlos FloresResearch Unit, Hospital Universitario NS de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Spain; Instituto Tecnológico y de Energías Renovables (ITER, S.A.), Santa Cruz de Tenerife, Spain.
Tasha E FingerlinCenter for Genes, Environment and Health, National Jewish Health, Denver, CO, USA; Department of Biostatistics and Informatics, University of Colorado, Denver, CO, USA.
Justin M OldhamDepartment of Internal Medicine, University of California Davis, Davis, CA, USA.
Beatriz Guillen-GuioResearch Unit, Hospital Universitario NS de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.
Shwu-Fan MaSection of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA.
Tsukasa OkamotoDepartment of Medicine, University of Colorado Denver, Denver, CO, USA.
Alison E JohnDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK.
Ma'en ObeidatThe University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
Ivana V YangCenter for Genes, Environment and Health, National Jewish Health, Denver, CO, USA; Department of Medicine, University of Colorado Denver, Denver, CO, USA.
Amanda HenryDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK.
Richard B HubbardNational Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK; Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
Vidya NavaratnamNational Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK; Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
Gauri SainiDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK.
Norma ThompsonDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK.
Helen L BoothDepartment of Thoracic Medicine, University College London Hospitals, London, UK.
Simon P HartRespiratory Research Group, Centre for Cardiovascular and Metabolic Research, The Hull York Medical School, Hull, UK.
Mike R HillClinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Nik HiraniMRC Centre for Inflammation Research at the University of Edinburgh, Edinburgh, UK.
Toby M MaherNIHR Respiratory Biomedical Research Unit, Royal Brompton Hospital, London, UK; Fibrosis Research Group, Inflammation, Repair and Development Section, National Heart and Lung Institute, Imperial College, London, UK.
Robin J McAnultyUCL Respiratory Centre for Inflammation and Tissue Repair, University College London, London, UK.
Ann B MillarAcademic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK.
Philip L MolyneauxNIHR Respiratory Biomedical Research Unit, Royal Brompton Hospital, London, UK; Fibrosis Research Group, Inflammation, Repair and Development Section, National Heart and Lung Institute, Imperial College, London, UK.
Helen ParfreyRespiratory Medicine, Papworth Hospital, Cambridge, UK.
Doris M RasslDepartment of Pathology, Papworth Hospital, Cambridge, UK.
Moira K B WhyteMRC Centre for Inflammation Research at the University of Edinburgh, Edinburgh, UK.
William A FahyFibrosis Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
Richard P MarshallFibrosis Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
Eunice OballaFibrosis Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
Yohan BosséInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Department of Molecular Medicine, Laval University, Quebec City, QC, Canada.
David C NickleMerck Research Laboratories, Genetics and Pharmacogenomics, Boston, MA, USA.
Don D SinThe University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada; Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Wim TimensDepartment of Pathology and Medical Biology, University Medical Centre Groningen, Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, Netherlands.
Nick ShrineDepartment of Health Sciences, University of Leicester, Leicester, UK.
Ian SayersDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK.
Ian P HallDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK.
Imre NothSection of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA.
David A SchwartzCenter for Genes, Environment and Health, National Jewish Health, Denver, CO, USA; Department of Medicine, University of Colorado Denver, Denver, CO, USA; Department of Immunology, University of Colorado Denver, Denver, CO, USA.
Martin D TobinDepartment of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Louise V WainDepartment of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK. Electronic address: lvw1@leicester.ac.uk.
R Gisli JenkinsDivision of Respiratory Medicine, University of Nottingham, Nottingham, UK; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals, Nottingham, UK; Nottingham Molecular Pathology Node, University of Nottingham, Nottingham, UK.
University of Nottingham · GBNottingham Biomedical Research Centre · GBGlaxoSmithKline (United Kingdom) · GBUniversity of Colorado Denver · USPapworth Hospital · GBUniversity of British Columbia · CAUniversity of Chicago · USUniversity of Leicester · GBCentre for Inflammation Research · GBGlenfield Hospital · GBHospital Universitario de Canarias · ESHull York Medical School · GBImperial College London · GBMerck & Co., Inc., Rahway, NJ, USA (United States) · USNational Institute for Health Research · GBNational Jewish Health · USRoyal Brompton Hospital · GBUniversidad de La Laguna · ESUniversité Laval · CAUniversity College Hospital · GB

Funding

Mechanisms of Familial Pulmonary FibrosisP01HL092870 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLACKWELL, TIMOTHY S. · 2010 to 2020
$21.6M
Role of Genetics in Idiopathic Pulmonary Fibrosis (IPF)R01HL097163 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI FINGERLIN, TASHA E., SCHWARTZ, DAVID ALBERT · 2009 to 2018
$16.4M
Functional Genetics in Idiopathic Pulmonary FibrosisR33HL120770 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHWARTZ, DAVID ALBERT · 2016 to 2018
$1.6M
Elucidating the Genomic Determinants of Outcomes in Idiopathic Pulmonary FibrosisK23HL138190 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OLDHAM, JUSTIN M · 2017 to 2021
$914k
Medical Research Council G0901226Medical Research Council G0902313Medical Research Council G1000861Medical Research Council MC_PC_12010Medical Research Council MC_QA137853Medical Research Council MC_U137686855Medical Research Council MR/N005953/1Medical Research Council MR/N011317/1NHLBI NIH HHS K23 HL138190NHLBI NIH HHS P01 HL092870NHLBI NIH HHS R01 HL097163NHLBI NIH HHS R33 HL120770Wellcome Trust 202849/Z/16/Z
6 · The paper itself

Abstract

backgroundIdiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified a significant genetic risk associated with the development of IPF; however, mechanisms by which genetic risk factors promote IPF remain unclear. We aimed to identify genetic variants associated with IPF susceptibility and provide mechanistic insight using gene and protein expression analyses.

methodsWe used a two-stage approach: a genome-wide association study in patients with IPF of European ancestry recruited from nine different centres in the UK and controls selected from UK Biobank (stage 1) matched for age, sex, and smoking status; and a follow-up of associated genetic variants in independent datasets of patients with IPF and controls from two independent US samples from the Chicago consortium and the Colorado consortium (stage 2). We investigated the effect of novel signals on gene expression in large transcriptomic and genomic data resources, and examined expression using lung tissue samples from patients with IPF and controls.

findings602 patients with IPF and 3366 controls were selected for stage 1. For stage 2, 2158 patients with IPF and 5195 controls were selected. We identified a novel genome-wide significant signal of association with IPF susceptibility near A-kinase anchoring protein 13 (AKAP13; rs62025270, odds ratio [OR] 1·27 [95% CI 1·18-1·37], p=1·32 × 10

interpretationAKAP13 is a Rho guanine nucleotide exchange factor regulating activation of RhoA, which is known to be involved in profibrotic signalling pathways. The identification of AKAP13 as a susceptibility gene for IPF increases the prospect of successfully targeting RhoA pathway inhibitors in patients with IPF.

fundingUK Medical Research Council, National Heart, Lung, and Blood Institute of the US National Institutes of Health, Agencia Canaria de Investigación, Innovación y Sociedad de la Información, Spain, UK National Institute for Health Research, and the British Lung Foundation.

Indexed as

Genetic VariationAgedA Kinase Anchor ProteinsAlveolar Epithelial CellsCase-Control StudiesEuropeFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIdiopathic Pulmonary FibrosisMaleMiddle AgedMinor Histocompatibility AntigensProto-Oncogene ProteinsrhoA GTP-Binding ProteinAKAP13 protein, humanA Kinase Anchor ProteinsMinor Histocompatibility AntigensProto-Oncogene ProteinsrhoA GTP-Binding ProteinRHOA protein, humanRho Guanine Nucleotide Exchange FactorsRNA, Messenger

Identifiers

PMID29066090
PMCPMC5666208
OpenAlexW2767079004

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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.