Evidence map›Paper›PMID 34237330›Full record

ArticleChest2022

An Integrative Genomic Strategy Identifies sRAGE as a Causal and Protective Biomarker of Lung Function.

Joshua Keefe, Chen Yao, Shih-Jen Hwang, Paul Courchesne, Gha Young Lee, Josée Dupuis, Joseph P Mizgerd, George O'Connor, George R Washko, Michael H Cho and 2 more

Open access · greenAbstract read
In one paragraph

Article in Chest, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

10 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Observational
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  4. Article
  5. Article
  6. Article
  7. Proteomic Biomarkers of Quantitative Interstitial Abnormalities in COPDGene and CARDIA Lung Study.American journal of respiratory and critical care medicine · 2024
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Joshua KeefeFramingham Heart Study, Framingham, MA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Chen YaoFramingham Heart Study, Framingham, MA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Shih-Jen HwangFramingham Heart Study, Framingham, MA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Paul CourchesneFramingham Heart Study, Framingham, MA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Gha Young LeeFramingham Heart Study, Framingham, MA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA.
Joseph P MizgerdPulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA.
George O'ConnorPulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA.
George R WashkoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Michael H ChoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Edwin K SilvermanDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Daniel LevyFramingham Heart Study, Framingham, MA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Electronic address: levyd@nih.gov.
National Institutes of Health · USBoston University · USBrigham and Women's Hospital · USNational Heart Lung and Blood Institute · US

Funding

Framingham Project/LevyZIAHL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2009 to 2025
$51.1M
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195
6 · The paper itself

Abstract

backgroundThere are few clinically useful circulating biomarkers of lung function and lung disease. We hypothesized that genome-wide association studies (GWAS) of circulating proteins in conjunction with GWAS of pulmonary traits represents a clinically relevant approach to identifying causal proteins and therapeutically useful insights into mechanisms related to lung function and disease. STUDY QUESTION: Can an integrative genomic strategy using GWAS of plasma soluble receptor for advanced glycation end-products (sRAGE) levels in conjunction with GWAS of lung function traits identify putatively causal relations of sRAGE to lung function? STUDY DESIGN AND

methodsPlasma sRAGE levels were measured in 6,861 Framingham Heart Study participants and GWAS of sRAGE was conducted to identify protein quantitative trait loci (pQTL), including cis-pQTL variants at the sRAGE protein-coding gene locus (AGER). We integrated sRAGE pQTL variants with variants from GWAS of lung traits. Colocalization of sRAGE pQTL variants with lung trait GWAS variants was conducted, and Mendelian randomization was performed using sRAGE cis-pQTL variants to infer causality of sRAGE for pulmonary traits. Cross-sectional and longitudinal protein-trait association analyses were conducted for sRAGE in relation to lung traits.

resultsColocalization identified shared genetic signals for sRAGE with lung traits. Mendelian randomization analyses suggested protective causal relations of sRAGE to several pulmonary traits. Protein-trait association analyses demonstrated higher sRAGE levels to be cross-sectionally and longitudinally associated with preserved lung function.

interpretationsRAGE is produced by type I alveolar cells, and it acts as a decoy receptor to block the inflammatory cascade. Our integrative genomics approach provides evidence for sRAGE as a causal and protective biomarker of lung function, and the pattern of associations is suggestive of a protective role of sRAGE against restrictive lung physiology. We speculate that targeting the AGER/sRAGE axis may be therapeutically beneficial for the treatment and prevention of inflammation-related lung disease.

Indexed as

AdultAgedFemaleForced Expiratory VolumeGenome-Wide Association StudyGenomicsHumansLungLung DiseasesMaleMendelian Randomization AnalysisMiddle AgedProtective FactorsQuantitative Trait LociReceptor for Advanced Glycation End ProductsRespiratory Function TestsAGER protein, humanReceptor for Advanced Glycation End ProductsCOPDMendelian randomizationspirometrysRAGE

Identifiers

PMID34237330
PMCPMC8783029
OpenAlexW3182557977

What OpenQuestion holds

Textmetadata
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.