Evidence mapPaperPMID 29566699Full record

SynthesisRespiratory research2018

Integrative genomics identifies new genes associated with severe COPD and emphysema.

Phuwanat Sakornsakolpat, Jarrett D Morrow, Peter J Castaldi, Craig P Hersh, Yohan Bossé, Edwin K Silverman, Ani Manichaikul, Michael H Cho

2 registry-linked trialsOpen access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Respiratory research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.4field-weighted citation impact, top 11% 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.

NCT00292552 completednot on this map

A Multicentre 3 Year Longitudinal Prospective Study to Identify Novel Endpoints and Compare These With Forced Expiratory Volume in 1 Second (FEV1) for Their Ability to Measure and Predict COPD Severity and Its Progression Over Time

TypeobservationalSponsorGlaxoSmithKlineRan2005 to 2010Enrolled2,747ConditionsPulmonary Disease, Chronic ObstructiveArmsNovel endpoint determination
NCT00608764 active not recruitingnot on this map

Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene)

TypeobservationalSponsorBrigham and Women's HospitalRan2007 to 2028Enrolled10,718ConditionsPulmonary Disease, Chronic Obstructive, Emphysema, Bronchitis, Chronic
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.American journal of respiratory and critical care medicine · 2024
    Article
  5. Article
  6. Transcriptome-Wide Association Study of Idiopathic Pulmonary Fibrosis Survival IdentifiesAmerican journal of respiratory and critical care medicine · 2024
    Article
  7. Breathing new life into the study of COPD with genes identified from genome-wide association studies.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  8. Blood-based Transcriptomic and Proteomic Biomarkers of Emphysema.American journal of respiratory and critical care medicine · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Artificial Intelligence Techniques to Predict the Airway Disorders Illness: A Systematic Review.Archives of computational methods in engineering : state of the art reviews · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Identifying Chronic Obstructive Pulmonary Disease Genes: Shining the Light on Dark DNA.American journal of respiratory cell and molecular biology · 2019
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Phuwanat SakornsakolpatChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Room 451, Boston, MA, 02115, USA.
Jarrett D MorrowChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Room 451, Boston, MA, 02115, USA.
Peter J CastaldiChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Room 451, Boston, MA, 02115, USA.
Craig P HershChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Room 451, Boston, MA, 02115, USA.
Yohan BosséDepartment of Molecular Medicine, Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, Quebec, Canada.
Edwin K SilvermanChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Room 451, Boston, MA, 02115, USA.
Ani ManichaikulDepartment of Public Health Sciences, Center for Public Health Genomics and Biostatistics Section, University of Virginia, Charlottesville, VA, USA.
Michael H ChoChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Room 451, Boston, MA, 02115, USA. remhc@channing.harvard.edu.
Brigham and Women's Hospital · USSiriraj Hospital · THUniversité Laval · CAUniversity of Virginia · US

Funding

Respiratory Computational Discovery CoreP01HL114501 · WEILL MEDICAL COLL OF CORNELL UNIV · 2025 to 2025
$2.5M
Impact of CPAP on Functional Outcomes in Milder OSAR01HL076101 · UNIVERSITY OF PENNSYLVANIA · 2003 to 2005
$1.9M
Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung AbnormalitiesR01HL135142 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$1.5M
Modeling of Lung HIV Cytokine/Chemokine NetworksR01HL076114 · BOSTON MEDICAL CENTER · 2003 to 2005
$1.4M
CLINICAL COORDINATING CENTER FOR LVRS-N01HR76119-268076119N01HR076119 · JOHNS HOPKINS UNIVERSITY · 1997 to 2005
$871k
Community Assist of Southern ArizonaR25ES011080 · CHILD AND FAMILY RESOURCES, INC. · 2001 to 2004
$771k
Neurotrophins and Development of Baroreceptor PathwaysR01HL076113 · OREGON HEALTH AND SCIENCE UNIVERSITY · 2005 to 2005
$312k
Training Program in Academic Pulmonary MedicineT32HL076118 · EMORY UNIVERSITY · 2004 to 2005
$261k
Cardiovascular Development and Disease in the YoungT32HL076116 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2004 to 2005
$236k
LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTERN01HR076118 · UNIVERSITY OF WASHINGTON · 1997 to 2000
$225k
LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTERN01HR076113 · UNIVERSITY OF PENNSYLVANIA · 1997 to 2000
$208k
CLNICAL CENTER FOR LVRSN01HR076104 · CEDARS-SINAI MEDICAL CENTER · 1997 to 2000
$153k
NHLBI NIH HHS K25 HL136846NHLBI NIH HHS N01 HR076101NHLBI NIH HHS N01 HR076102NHLBI NIH HHS N01 HR076103NHLBI NIH HHS N01 HR076104NHLBI NIH HHS N01 HR076105NHLBI NIH HHS N01 HR076106NHLBI NIH HHS N01 HR076107NHLBI NIH HHS N01 HR076108NHLBI NIH HHS N01 HR076109NHLBI NIH HHS N01 HR076110NHLBI NIH HHS N01 HR076111NHLBI NIH HHS N01 HR076112NHLBI NIH HHS N01 HR076113NHLBI NIH HHS N01 HR076114NHLBI NIH HHS N01 HR076115NHLBI NIH HHS N01 HR076116NHLBI NIH HHS N01 HR076118NHLBI NIH HHS N01 HR076119NHLBI NIH HHS P01 HL114501NHLBI NIH HHS R01 HL086936NHLBI NIH HHS R01 HL089856NHLBI NIH HHS R01 HL089897NHLBI NIH HHS R01 HL089897 and R01 HL089856NHLBI NIH HHS R01 HL113264NHLBI NIH HHS R01 HL113264, R01 HL086936, P01 HL114501, R01 HL137927, and R01 HL135142NHLBI NIH HHS R01 HL124233NHLBI NIH HHS R01 HL125583NHLBI NIH HHS R01 HL131565NHLBI NIH HHS R01 HL135142NHLBI NIH HHS R01 HL137927NHLBI NIH HHS U01 HL089856NHLBI NIH HHS U01 HL089897NIEHS NIH HHS R25 ES011080
6 · The paper itself

Abstract

backgroundGenome-wide association studies have identified several genetic risk loci for severe chronic obstructive pulmonary disease (COPD) and emphysema. However, these studies do not fully explain disease heritability and in most cases, fail to implicate specific genes. Integrative methods that combine gene expression data with GWAS can provide more power in discovering disease-associated genes and give mechanistic insight into regulated genes.

methodsWe applied a recently described method that imputes gene expression using reference transcriptome data to genome-wide association studies for two phenotypes (severe COPD and quantitative emphysema) and blood and lung tissue gene expression datasets. We further tested the potential causality of individual genes using multi-variant colocalization.

resultsWe identified seven genes significantly associated with severe COPD, and five genes significantly associated with quantitative emphysema in whole blood or lung. We validated results in independent transcriptome databases and confirmed colocalization signals for PSMA4, EGLN2, WNT3, DCBLD1, and LILRA3. Three of these genes were not located within previously reported GWAS loci for either phenotype. We also identified genetically driven pathways, including those related to immune regulation.

conclusionsAn integrative analysis of GWAS and gene expression identified novel associations with severe COPD and quantitative emphysema, and also suggested disease-associated genes in known COPD susceptibility loci.

trial registrationNCT00608764 , Registry: ClinicalTrials.gov, Date of Enrollment of First Participant: November 2007, Date Registered: January 28, 2008 (retrospectively registered); NCT00292552 , Registry: ClinicalTrials.gov, Date of Enrollment of First Participant: December 2005, Date Registered: February 14, 2006 (retrospectively registered).

Indexed as

Severity of Illness IndexClinical Trials as TopicCohort StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyGenomicsHumansPulmonary Disease, Chronic ObstructivePulmonary EmphysemaChronic obstructive pulmonary diseaseEmphysemaGene expressionGenome-wide association studies

Identifiers

PMID29566699
PMCPMC5863845
OpenAlexW2802728013

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

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 Socratic graph.