SynthesisNature communications2015
Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis.
Registry-linked trialOpen access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00037765 (Gene Modifiers of Cystic Fibrosis Lung Disease), which is not on this map. Cited by 167 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
167citing papers in PubMed, 1 pooled it
25.1field-weighted citation impact, top 1% of its field
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.
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.
Gene Modifiers of Cystic Fibrosis Lung Disease
Who cites it
167 citing papers in PubMed, 1 synthesis or guideline pooled it, 295 citations in OpenAlex.
- Impact of Gene Modifiers on Cystic Fibrosis Phenotypic Profiles: A Systematic Review.Human mutation · 2024Pooled it
- Impact of Genetics on Endocrine Manifestations of Cystic Fibrosis.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2026Review
- Complex structural variation, phylogeny, and disease associations of the mucin pangenome.medRxiv : the preprint server for health sciences · 2026Article
- Beyond BMI: Nutritional Recovery and Functional Implications of CFTR Modulators in Cystic Fibrosis.Biology · 2026Review
- Cholinergic signaling modulates intestinal pathophysiology in a Drosophila model of cystic fibrosis.PLoS genetics · 2026Article
- A deep ensemble encoder network method for improved polygenic risk score prediction.BioData mining · 2026Article
- GA4GH phenopacket-driven characterization of genotype-phenotype correlations in Mendelian disorders.American journal of human genetics · 2026Article
- Distinct regulatory elements of SLC6A14 expression contribute to modification of cystic fibrosis phenotypes.Human genetics · 2026Article
- L467F;F508del Complex Allele in a Heterozygous State with CFTRdele2,3: What to Expect from CFTR Modulators?International journal of molecular sciences · 2025Article
- Single-cell RNA-sequencing co-expression analysis with CFTR and CF modifier genes in lung tissue.Scientific reports · 2025Article
- Cystic fibrosis-related kidney disease-emerging morbidity and disease modifier.Pediatric nephrology (Berlin, Germany) · 2025Review
- Role of S1PR1 in Modulating Airway Epithelial Responses toPathogens (Basel, Switzerland) · 2025Article
- On the analysis of genetic association with long-read sequencing data.PLoS genetics · 2025Article
- A Robust Association Test Leveraging Unknown Genetic Interactions: Application to Cystic Fibrosis Lung Disease.Genetic epidemiology · 2025Article
- An in vitro model of the epithelial airway reveals a key function for EHF in lung homeostasis and disease.Disease models & mechanisms · 2025Article
- The Frequency and Potential Implications of HFE Genetic Variants in Children With Cystic Fibrosis.Pediatric pulmonology · 2025Article
- Reconsidering the Diagnosis: Abnormal Sweat Chloride Tests in Non-CF Bronchiectasis.Pediatric pulmonology · 2025Article
- Nasal cells as a bronchial cell surrogate for pre-clinical assessment of drug response in cystic fibrosis.Frontiers in pharmacology · 2025Article
- Genome-wide association study of susceptibility toThe European respiratory journal · 2024Article
- LMTK2 switches on canonical TGF-β1 signaling in human bronchial epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2024Article
107 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
31 authors at 9 institutions in 3 countries.
Harriet CorvolAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Trousseau, Pediatric Pulmonary Department; Institut National de la Santé et la Recherche Médicale (INSERM) U938, Paris 75012, France.
Scott M BlackmanDivision of Pediatric Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.ORCID http://orcid.org/0000-0002-4532-6421
Pierre-Yves BoëlleSorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Paris 75005, France.
Paul J GallinsDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Rhonda G PaceMarsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Jaclyn R StonebrakerMarsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Frank J AccursoDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Center, Aurora, Colorado 80045, USA.
Annick ClementAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Trousseau, Pediatric Pulmonary Department; Institut National de la Santé et la Recherche Médicale (INSERM) U938, Paris 75012, France.
Joseph M CollacoDivision of Pediatric Pulmonology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Hong DangMarsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Anthony T DangMarsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Arianna FrancaMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Jiafen GongProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
Loic GuillotAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Trousseau, Pediatric Pulmonary Department; Institut National de la Santé et la Recherche Médicale (INSERM) U938, Paris 75012, France.
Katherine KeenanProgram in Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
Weili LiProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
Fan LinProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
Michael V PatroneMarsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Karen S RaraighMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Lei SunDepartment of Statistical Sciences, University of Toronto, Toronto, Ontario, Canada M5S 3G3.
Yi-Hui ZhouBioinformatics Research Center and Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA.
Wanda K O'NealMarsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Marci K SontagDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Anschutz Medical Center, Aurora, Colorado 80045, USA.
Hara LevyDivision of Pulmonary Medicine, Department of Pediatrics, Stanley Manne Research Institute, Northwestern University Feinberg School of Medicine, Ann and Robert Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
Peter R DurieProgram in Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
Johanna M RommensProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
Mitchell L DrummDepartment of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Fred A WrightBioinformatics Research Center and Department of Statistics, North Carolina State University, Raleigh, North Carolina 27695, USA.
Lisa J StrugProgram in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
Garry R CuttingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Michael R KnowlesMarsico Lung Institute/UNC CF Research Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
University of North Carolina at Chapel Hill · USJohns Hopkins University · USHospital for Sick Children · CAInserm · FRUniversity of Toronto · CAColorado School of Public Health · USNorth Carolina State University · USCase Western Reserve University · USNorthwestern University · US
Funding
JHU-UMD Diabetes Research CenterP30DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI WONDISFORD, FREDRIC E. · 2013 to 2017
$9.7MGene Modifiers in CF Lung DiseaseR01HL068890 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KNOWLES, MICHAEL R · 2001 to 2014
$9.5MGenetic Modifiers of Cystic Fibrosis: Sibling StudyR01HL068927 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CUTTING, GARRY R · 2001 to 2011
$8.9MMolecular Phenotypes for Cystic Fibrosis Lung DiseaseR01HL095396 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KNOWLES, MICHAEL R, WRIGHT, FRED A. · 2008 to 2011
$2.9MDeterminants of pancreatic injury in cystic fibrosisR01DK061886 · NIDDK · CHILDREN'S HOSPITAL OF DENVER · PI ACCURSO, FRANK J. · 2001 to 2004
$2.3MIntegration of Genomics with Genetics - Molecular Phenotypes for CF Lung DiseaseDP2OD007031 · OD · MEDICAL COLLEGE OF WISCONSIN · PI LEVY, HARA · 2010 to 2010
$2.2MGenetic modifiers of diabetes in cystic fibrosisK23DK083551 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BLACKMAN, SCOTT M · 2009 to 2013
$877kPermutation Approximations for Next Generation AssociationR21HG007840 · NHGRI · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI ZHOU, YIHUI · 2015 to 2016
$417kCanadian Institutes of Health Research MOP 258916NHGRI NIH HHS R21 HG007840NHGRI NIH HHS R21HG007840NHLBI NIH HHS R01 HL068890NHLBI NIH HHS R01HL068890NHLBI NIH HHS R01 HL068927NHLBI NIH HHS R01 HL095396NHLBI NIH HHS R01HL095396NHLBI NIH HHS R01HL68927NIDDK NIH HHS 1R01DK61886-01NIDDK NIH HHS K23 DK083551NIDDK NIH HHS K23DK083551NIDDK NIH HHS P30 DK079637NIDDK NIH HHS P30DK079637NIDDK NIH HHS R01 DK061886NIH HHS 1DP2OD007031NIH HHS DP2 OD007031
Abstract
The identification of small molecules that target specific CFTR variants has ushered in a new era of treatment for cystic fibrosis (CF), yet optimal, individualized treatment of CF will require identification and targeting of disease modifiers. Here we use genome-wide association analysis to identify genetic modifiers of CF lung disease, the primary cause of mortality. Meta-analysis of 6,365 CF patients identifies five loci that display significant association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3 × 10(-11)), chr5p15.3 (SLC9A3; P=6.8 × 10(-12)), chr6p21.3 (HLA Class II; P=1.2 × 10(-8)) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 × 10(-9)) contain genes of high biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13 (EHF/APIP; P=1.9 × 10(-10)), was previously shown to be associated with lung disease. These results provide new insights into potential targets for modulating lung disease severity in CF.
Indexed as
Genome-Wide Association StudyAdolescentAdultAmino Acid Transport SystemsAmino Acid Transport Systems, NeutralChildCystic FibrosisFemaleHumansLungMaleMiddle AgedMucin-4MucinsSeverity of Illness IndexTranscription FactorsAmino Acid Transport SystemsAmino Acid Transport Systems, NeutralEHF protein, humanMUC20 protein, humanMUC4 protein, humanMucin-4MucinsSLC6A14 protein, humanTranscription Factors
Identifiers
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LicenceCC BY
Read underepoch 390
Registered trials
NCT00037765ClinicalTrials.gov
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.