SynthesisPLoS genetics2012
Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 15 of them syntheses that pooled it.
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102citing papers in PubMed, 15 pooled it
10.6field-weighted citation impact, top 1% of its field
What it found
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The trial behind it
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Who cites it
102 citing papers in PubMed, 15 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- Exploiting meta-analysis of genome-wide interaction with serum 25-hydroxyvitamin D to identify novel genetic loci associated with pulmonary function.The American journal of clinical nutrition · 2024Pooled it
- Interaction between Genetic Risk Scores for reduced pulmonary function and smoking, asthma and endotoxin.Thorax · 2021Pooled it
- Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.Gastroenterology · 2020Pooled it
- Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.Nature communications · 2018Pooled it
- Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects.American journal of respiratory cell and molecular biology · 2017Pooled it
- Pooled it
- A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease.The pharmacogenomics journal · 2016Pooled it
- Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.Nature communications · 2016Pooled it
- Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.Nature communications · 2015Pooled it
- A genome-wide pleiotropy scan for prostate cancer risk.European urology · 2015Pooled it
- Modulation of genetic associations with serum urate levels by body-mass-index in humans.PloS one · 2015Pooled it
- Post-GWAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79,000 women.Human molecular genetics · 2014Pooled it
- Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respiratory research · 2014Pooled it
- APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.The European respiratory journal · 2014Pooled it
- Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis.The Lancet. Respiratory medicine · 2014Pooled it
- Defective alveolar regeneration in emphysema: identifying dysfunctional cellular crosstalk and novel therapeutic opportunities for tissue repair.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- KCNJ2 is Required for NLRP3 Inflammasome Activation That Drives Allergic Airway Inflammation and Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interactive Effects of Genetic Susceptibility and Early-Life Tobacco Smoke Exposure on the Asthma-Eczema Complex Phenotype in Children: 6-Year Follow-Up Case-Control Study.International journal of molecular sciences · 2025Article
- Bidirectional genetic links between chronic obstructive pulmonary disease and frailty: Genome-wide association study insights.PloS one · 2025Article
- The association between patterns of exposure to adverse life events and the risk of chronic kidney disease: a prospective cohort study of 140,997 individuals.Translational psychiatry · 2024Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
90 authors at 20 institutions in 11 countries.
Dana B HancockBehavioral Health Epidemiology Program, Research Triangle Institute International, Research Triangle Park, North Carolina, USA.
María Soler Artigas
Sina A Gharib
Amanda Henry
Ani Manichaikul
Adaikalavan Ramasamy
Daan W Loth
Medea Imboden
Beate Koch
Wendy L McArdle
Albert V Smith
Joanna Smolonska
Akshay Sood
Wenbo Tang
Jemma B Wilk
Guangju Zhai
Jing Hua Zhao
Hugues Aschard
Kristin M Burkart
Ivan Curjuric
Mark Eijgelsheim
Paul Elliott
Xiangjun Gu
Tamara B Harris
Christer Janson
Georg Homuth
Pirro G Hysi
Jason Z Liu
Laura R Loehr
Kurt Lohman
Ruth J F Loos
Alisa K Manning
Kristin D Marciante
Ma'en Obeidat
Dirkje S Postma
Melinda C Aldrich
Guy G Brusselle
Ting-hsu Chen
Gudny Eiriksdottir
Nora Franceschini
Joachim Heinrich
Jerome I Rotter
Cisca Wijmenga
O Dale Williams
Amy R Bentley
Albert Hofman
Cathy C Laurie
Thomas Lumley
Alanna C Morrison
Bonnie R Joubert
Fernando Rivadeneira
David J Couper
Stephen B Kritchevsky
Yongmei Liu
Matthias Wjst
Louise V Wain
Judith M Vonk
André G Uitterlinden
Thierry Rochat
Stephen S Rich
Bruce M Psaty
George T O'Connor
Kari E North
Daniel B Mirel
Bernd Meibohm
Lenore J Launer
Kay-Tee Khaw
Anna-Liisa Hartikainen
Christopher J Hammond
Sven Gläser
Jonathan Marchini
Peter Kraft
Nicholas J Wareham
Henry Völzke
Bruno H C Stricker
Timothy D Spector
Nicole M Probst-Hensch
Deborah Jarvis
Marjo-Riitta Jarvelin
Susan R Heckbert
Vilmundur Gudnason
H Marike Boezen
R Graham Barr
Patricia A Cassano
David P Strachan
Myriam Fornage
Ian P Hall
Josée Dupuis
Martin D Tobin
Stephanie J London
Erasmus MC · NLKing's College London · GBUniversity Medical Center Groningen · NLUniversity of North Carolina at Chapel Hill · USUniversity of Washington · USHarvard University · USMRC Epidemiology Unit · GBUniversitätsmedizin Greifswald · DEUniversity of Leicester · GBUniversity of Nottingham · GBWake Forest University · USBrown Foundation · USColumbia University · USCornell University · USFramingham Heart Study · USHelmholtz Zentrum München · DEIcelandic Heart Association · ISImperial College London · GBNational Institute on Aging · USUniversity of Basel · CH
Funding
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MType 1 Diabetes Genetics ConsortiumU01DK062418 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RICH, STEPHEN S. · 2002 to 2007
$59.8MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MCTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MA Center for GEI Association StudiesU01HG004424 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2010
$21.4MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MPulmonary microvascular perfusion in the Multi-Ethnic Study of AtherosclerosisR01HL077612 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2004 to 2026
$18.8MUCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5MEpidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MCancer Research UK 14136Department of Health SRF/01/010Intramural NIH HHS Z01 ES043012Medical Research Council G0000934Medical Research Council G0401527Medical Research Council G0902313Medical Research Council G1000143Medical Research Council G1000861Medical Research Council MC_U106179471Medical Research Council MC_U106188470NCATS NIH HHS UL1 TR000124NCRR NIH HHS RR-024156NCRR NIH HHS UL1 RR024156NCRR NIH HHS UL1 RR025005NCRR NIH HHS UL1RR025005NCRR NIH HHS UL 1RR033176NEI NIH HHS 1R01EY018246NEI NIH HHS R01 EY018246NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01HG004402NHGRI NIH HHS U01 HG004424NHGRI NIH HHS U01-HG-004424NHGRI NIH HHS U01 HG004446NHGRI NIH HHS U01-HG-004446NHGRI NIH HHS U01 HG004729NHGRI NIH HHS U01-HG-004729NHLBI NIH HHS 5R01HL087679-02NHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HL075366NHLBI NIH HHS HL080295NHLBI NIH HHS HL087652NHLBI NIH HHS HL105756NHLBI NIH HHS N01 HC005187NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC045134NHLBI NIH HHS N01 HC045204NHLBI NIH HHS N01 HC045205NHLBI NIH HHS N01 HC048047NHLBI NIH HHS N01 HC048048NHLBI NIH HHS N01 HC048049NHLBI NIH HHS N01 HC048050NHLBI NIH HHS N01-HC-05187NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC075150NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095095NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N01 HC-15103NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS N01-HC-35129NHLBI NIH HHS N01-HC-45133NHLBI NIH HHS N01-HC-45134NHLBI NIH HHS N01-HC-45204NHLBI NIH HHS N01-HC-45205NHLBI NIH HHS N01-HC-48047NHLBI NIH HHS N01-HC-48048NHLBI NIH HHS N01-HC-48049NHLBI NIH HHS N01-HC-48050NHLBI NIH HHS N01 HC-55222NHLBI NIH HHS N01-HC-75150NHLBI NIH HHS N01-HC-85079NHLBI NIH HHS N01-HC-85080NHLBI NIH HHS N01-HC-85081NHLBI NIH HHS N01-HC-85082NHLBI NIH HHS N01-HC-85083NHLBI NIH HHS N01-HC-85084NHLBI NIH HHS N01-HC-85085NHLBI NIH HHS N01-HC-85086NHLBI NIH HHS N01-HC-85239NHLBI NIH HHS N01-HC-95095NHLBI NIH HHS N01-HC-95159NHLBI NIH HHS N01-HC-95160NHLBI NIH HHS N01-HC-95161NHLBI NIH HHS N01-HC-95162NHLBI NIH HHS N01-HC-95163NHLBI NIH HHS N01-HC-95164NHLBI NIH HHS N01-HC-95165NHLBI NIH HHS N01-HC-95166NHLBI NIH HHS N01-HC-95167NHLBI NIH HHS N01-HC-95168NHLBI NIH HHS N01-HC-95169NHLBI NIH HHS N02-HL-6-4278NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL075366NHLBI NIH HHS R01 HL075476NHLBI NIH HHS R01 HL077612NHLBI NIH HHS R01-HL077612NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL084099NHLBI NIH HHS R01-HL-084099NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL087679NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01HL59367NHLBI NIH HHS RC1 HL100543NHLBI NIH HHS RC1-HL100543NHLBI NIH HHS U01 HL080295NIA NIH HHS 1R01AG032098-01A1NIA NIH HHS AG-023629NIA NIH HHS AG-027058NIA NIH HHS AG-15928NIA NIH HHS AG-20098NIA NIH HHS N01 AG012100NIA NIH HHS N01 AG062101NIA NIH HHS N01 AG062106NIA NIH HHS N01-AG-12100NIA NIH HHS N01AG2103NIA NIH HHS N01AG62101NIA NIH HHS N01AG62106NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG027058NIA NIH HHS R01 AG032098NIA NIH HHS R56 AG020098NIA NIH HHS R56 AG023629NIA NIH HHS RC1 AG035835NIA NIH HHS RC1AG035835NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R21 DK084529NIDDK NIH HHS R21DK084529NIDDK NIH HHS U01 DK062418NIDDK NIH HHS U01DK062418NIEHS NIH HHS Z01ES043012NIMH NIH HHS 1RL1MH083268-01NIMH NIH HHS 5R01MH63706:02NIMH NIH HHS R01 MH063706NIMH NIH HHS RL1 MH083268Wellcome Trust 068545/Z/02Wellcome Trust 076113/B/04/ZWellcome Trust 079895Wellcome Trust 090532
Abstract
Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
Indexed as
Genome-Wide Association StudyPulmonary Disease, Chronic ObstructiveSmokingForced Expiratory VolumeGene ExpressionGenome, HumanHLA-DQ AntigensHLA-DQ beta-ChainsHumansLungNerve Tissue ProteinsPolymorphism, Single NucleotidePotassium Channels, Inwardly RectifyingReceptors, Cell SurfaceSOX9 Transcription FactorVital CapacityDNER protein, humanHLA-DQA2 antigenHLA-DQ AntigensHLA-DQB1 antigenHLA-DQ beta-ChainsKCNJ2 protein, humanNerve Tissue ProteinsPotassium Channels, Inwardly RectifyingReceptors, Cell SurfaceSOX9 protein, humanSOX9 Transcription Factor
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