Evidence map›Paper›PMID 42261270›Full record

ArticleAmerican journal of respiratory and critical care medicine2026

Performance of age-adjusted whole genome sequencing telomere length in idiopathic pulmonary fibrosis.

John S Kim, Brody Receveur, David Zhang, Shwu-Fan Ma, Yong Huang, Claire McGroder, Rachel K Putman, Anna J Podolanczuk, Jerome I Rotter, Stephen S Rich and 22 more

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Article in American journal of respiratory and critical care medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

32 authors.

John S KimDepartment of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Brody ReceveurDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States.
David ZhangDepartment of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States.
Shwu-Fan MaDepartment of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Yong HuangDepartment of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Claire McGroderDepartment of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States.
Rachel K PutmanDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Anna J PodolanczukDivision of Pulmonary and Critical Care Medicine, Weill Cornell Medical Center, New York, NY, United States.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor, UCLA Medical Center, Torrance, CA, United States.ORCID 0000-0001-7191-1723
Stephen S RichDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States.
Kevin R FlahertyDepartment of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, United States.
Joyce S LeeDepartment of Medicine, University of Colorado, Aurora, CO, United States.
Joseph A LaskyDepartment of Medicine, Tulane University, New Orleans, LA, United States.
Ganesh RaghuDivision of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, United States.
Susan MurrayDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, United States.
Catherine SpinoDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, United States.
Fernando J MartinezDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, United States.
Andrea OhDepartment of Radiology, University of California, Los Angeles Medical Center, Los Angeles, CA, United States.
David A LynchDepartment of Radiology, National Jewish Health, Denver, CO, United States.
Stephen M HumphriesDepartment of Radiology, National Jewish Health, Denver, CO, United States.ORCID 0000-0002-5113-4530
Ayodeji AdegunsoyeSection of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, United States.
Justin M OldhamDepartment of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, United States.
Gary M HunninghakeDivision of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Christine Kim GarciaDepartment of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States.
Margaret TaubDepartment of Biostatistics, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, United States.
Rasika A MathiasGenomics and Precision Health Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
R Graham BarrDepartment of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States.
Imre NothDepartment of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Josyf C MychaleckyjDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States.ORCID 0000-0003-2595-0005
Ani ManichaikulDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States.
Chad A NewtonDivision of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.ORCID 0000-0001-5256-9029

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Genetic Epidemiology of COPDU01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2007 to 2021
$56.9M
GENETIC EPIDEMIOLOGY OF COPD (COPD GENE) TASK A: STUDY VISIT 4, COLLECTION OF COPDGENE STUDY DATA ANDBIOSPECIMENS AND OVERSIGHT OF THE COPDGENE STUDY75N92023D00011 · NHLBI · NATIONAL JEWISH HEALTH · PI NEWMAN, LEE S · 2023 to 2025
$29.6M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
Pulmonary Vascular Changes in Early Chronic Obstructive Pulmonary Disease (COPD)R01HL093081 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI R Graham BARR · 2008 to 2026
$17.2M
Task Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1M
TO EXERCISE OPTION PERIOD ONE (1) FOR TASK AREA A - MESA CORE OPERATIONS, FIELD CENTER.75N92020D00004 · NHLBI · NORTHWESTERN UNIVERSITY · PI SIEGEL, JONATHAN H · 2020 to 2025
$4.5M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00006 · NHLBI · UNIVERSITY OF MINNESOTA · PI PANKOW, JAMES S · 2020 to 2025
$4.4M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00003 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI POST, WENDY S · 2020 to 2025
$3.8M
Task Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00007 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BERTONI, ALAIN GERALD · 2020 to 2025
$3.5M
Broad Institute of MIT and Harvard 3U54HG003067-13S1Broad Institute of MIT and Harvard HHSN268201500014CIntramural Research Program of the National Institutes of Health NCT00608764Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study R01-HL077612Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study R01-HL093081Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study RC1-HL100543NHLBINHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS 75N92023D00011NHLBI NIH HHS 75N92025D00022NHLBI NIH HHS 75N92025D00024NHLBI NIH HHS 75N92025D00025NHLBI NIH HHS 75N92025D00026NHLBI NIH HHS 75N92025D00027NHLBI NIH HHS 75N92025D00028NHLBI NIH HHS DK063491NHLBI NIH HHS HHSN268201500003INHLBI NIH HHS K23-HL148498NHLBI NIH HHS K23-HL150301NHLBI 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 R01-135142NHLBI NIH HHS R01 HL093081NHLBI NIH HHS R01-HL103676NHLBI NIH HHS R01-HL105756NHLBI NIH HHS R01HL105756NHLBI NIH HHS R01-HL111024NHLBI NIH HHS R01-HL130974NHLBI NIH HHS R01-HL171918NHLBI NIH HHS R01-HL176659NHLBI NIH HHS R01-HL176839NHLBI NIH HHS U01HL089856NHLBI NIH HHS U01HL089897NHLBI NIH HHS UL1-TR-000040NHLBI NIH HHS UL1-TR-001079NHLBI NIH HHS UL1-TR-001420NHLBI NIH HHS UL1TR001881The Pulmonary Fibrosis Foundation Patient Registry UH3-HL145266the University of Washington Northwest Genomics Center 3R01 HL089856-08S1TOPMed Informatics Research Center 3R01HL-117626-02S1TOPMed Informatics Research Center HHSN268201800001ITOPMed Informatics Research Center HHSN268201800002ITOPMed Informatics Research Center R01HL-120393TOPMed Informatics Research Center U01HL-120393
6 · The paper itself

Abstract

rationaleWhole genome sequencing-estimated telomere length (WGS-TL) correlates with directly measured peripheral blood telomere length. However, raw WGS-TL does not account for normal age-related telomere attrition to identify patients with idiopathic pulmonary fibrosis (IPF) with pathologically short telomeres.

objectivesTo determine utility of age-adjusted WGS-TL to identify adults with telomere-related qualifying variants (TRQVs) and whether it associates with survival.

methodsWGS-TL from two samples of community-dwelling adults (MESA) and people who smoke cigarettes (COPDGene) were used to construct an age-adjusted WGS-TL nomogram (n = 9940) using linear regression models that regressed on raw WGS-TL and adjusted for chronologic age. Using this nomogram, age-adjusted WGS-TL was generated in IPF cases from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n = 825) to determine diagnostic performance characteristics for identifying TRQV and survival discrimination. MEASUREMENTS AND MAIN

resultsThere was a higher proportion of IPF patients from the PFF-PR with abnormally short age-adjusted WGS-TL <10th percentile (28%) compared with MESA (5%) or COPDGene (10%). Among IPF patients, age-adjusted WGS-TL <10th percentile outperformed raw WGS-TL <10th percentile at discriminating TRQV (area under the receiver operating curve = 0.66 [95% CI, 0.60-0.73] vs 0.62 [95% CI, 0.56-0.69]). At both the shorter age-adjusted and raw WGS-TL thresholds, specificity (0.74-0.99) was higher than sensitivity (0.10-0.58). Age-adjusted WGS-TL below the 10th percentile was associated with shorter 3-year transplant-free survival (HR, 1.35 [95% CI, 1.05-1.74]) but did not improve survival discrimination over clinical variables alone.

conclusionsAge-adjusted WGS-TL enables identification of IPF patients with pathologically short telomeres, modestly improves detection of TRQV, and associates with survival.

Indexed as

Idiopathic Pulmonary FibrosisTelomereWhole Genome SequencingAgedAged, 80 and overAge FactorsFemaleHumansMaleMiddle Agedpulmonary fibrosistelomere lengthwhole genome sequencing

Identifiers

PMID42261270
PMCPMC13624805

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