Evidence map›Paper›PMID 42085243›Full record

ArticleAmerican journal of respiratory and critical care medicine2026

Mosaic loss of Y chromosome associates with lung function, emphysema, and epigenetic aging.

Woei-Yuh Saw, Kangjin Kim, Yichen Huang, Jeong H Yun, Xiaolong Ma, Jason Bacon, Yash Pershad, Daniel Levy, George T O'Connor, Eric Boerwinkle and 21 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

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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

31 authors.

Woei-Yuh SawChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Kangjin KimChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Yichen HuangChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Jeong H YunChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Xiaolong MaDivision of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI, United States.
Jason BaconDepartment of Computer Science, Department of Biological Sciences, University of Wisconsin Milwaukee, Milwaukee, WI, United States.
Yash PershadDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.ORCID 0000-0002-2282-1403
Daniel LevyFramingham Heart Study, Framingham, MA, United States.
George T O'ConnorDepartment of Medicine, The Pulmonary Center , Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States.
Eric BoerwinkleHuman Genetics Center, Department of Epidemiology, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States.
R Graham BarrDepartment of Medicine, Columbia University Medical Center, New York, NY, United States.
Stephen S RichDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States.
Jerome I RotterDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States.ORCID 0000-0001-7191-1723
April P CarsonDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, United States.
Laura M RaffieldPopulation Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Sina A GharibCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States.
Traci M BartzDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, United States.
Bruce M PsatyDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA, United States.
Tamar SoferDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States.ORCID 0000-0001-8520-8860
Kari E NorthDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Robert C KaplanDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.ORCID 0000-0003-3271-801X
Elizabeth C OelsnerDivision of General Medicine, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States.
Ani ManichaikulDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States.
Alexander G BickDivision of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Paul ScheetDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA, United States.
NHLBI Trans-Omics for Precision Medicine Consortium
Yasminka A JakubekDepartment of Internal Medicine, University of Kentucky, Lexington, KY, United States.
Paul L AuerDivision of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI, United States.ORCID 0000-0003-1735-8044
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Dawn L DeMeoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.

Funding

UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Hazel B Nichols · 2001 to 2026
$36.3M
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
Imaging and multi-omics analyses to identify molecular subtypes of distinct emphysema patternsR01HL167072 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Adel El Boueiz · 2023 to 2026
$3.4M
Integrative genomic, transcriptomic and proteomic studies of pulmonary function and COPDR01HL153248 · NHLBI · UNIVERSITY OF VIRGINIA · PI CHO, MICHAEL H., MANICHAIKUL, ANI WANG · 2021 to 2024
$2.8M
Infrastructure for mentored access to CHS data and specimensR01HL172803 · NHLBI · UNIVERSITY OF WASHINGTON · PI James S Floyd, Michelle Christina Odden · 2025 to 2026
$2.7M
Networks Tools to Understand Sex- and Gender-Specific Drivers of DiseaseR01HG011393 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI DEMEO, DAWN L, QUACKENBUSH, JOHN · 2021 to 2024
$2.1M
Hypercoagulability and Chronic Lung Disease in Older AdultsK23HL130627 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI OELSNER, ELIZABETH · 2016 to 2019
$686k
Changes in the public health burden of tobacco use during the COVID-19 pandemic: the C4R StudyR21HL165405 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BALTE, PALLAVI P, OELSNER, ELIZABETH · 2022 to 2023
$452k
Respiratory health and cigar and pipe use in the NHLBI Pooled Cohorts StudyR21HL153700 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI OELSNER, ELIZABETH, SANCHEZ, TIFFANY RENEE · 2020 to 2021
$446k
Albuminuria and incident chronic lung disease exacerbations in five population-based cohortsR21HL129924 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI OELSNER, ELIZABETH · 2015 to 2016
$440k
Mentoring in Patient Oriented Research in Lung Disease through the Lens of Sex as a Biological VariableK24HL171900 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DAWN L DEMEO · 2024 to 2026
$386k
NHGRI NIH HHS R01 HG011393NHLBI NIH HHS 75N92023D00011NHLBI NIH HHS K23 HL130627NHLBI NIH HHS K24 HL171900NHLBI NIH HHS R01 HL153248NHLBI NIH HHS R01 HL167072NHLBI NIH HHS R01 HL172803NHLBI NIH HHS R21 HL129924NHLBI NIH HHS R21 HL153700NHLBI NIH HHS R21 HL165405NIEHS NIH HHS P30 ES010126Trans-Omics in Precision Medicine K23HL130627Trans-Omics in Precision Medicine R01HL153248Trans-Omics in Precision Medicine R21HL129924Trans-Omics in Precision Medicine R21HL153700Trans-Omics in Precision Medicine R21HL165405
6 · The paper itself

Abstract

rationaleAs the global population ages, identifying risk factors for age-related diseases, such as COPD, is crucial for public health. Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mosaicism event, but its relationship with pulmonary health remains undercharacterized.

objectivesTo examine the association between mLOY and pulmonary outcomes in men.

methodsLeveraging mLOY assessment (cell fraction ≥ 5%) in over 12 000 men, including 5097 from the COPDGene Study and 7235 from six additional cohorts in the Trans-Omics for Precision Medicine program, we investigated mLOY associations with respiratory outcomes and epigenetic aging using multivariable cross-sectional, longitudinal, and prospective models. Primary outcomes included spirometry, CT-based emphysema, and epigenetic pace of aging.

resultsThe prevalence of mLOY increased with age. Cross-sectionally, mLOY was associated with airflow obstruction, with reduced FEV1/FVC of 0.018 [95% CI, -0.030 to -0.006] in COPDGene and 0.020 [95% CI, -0.027 to -0.013] in TOPMed. mLOY was also associated with greater CT-quantified lung emphysema and faster pace epigenetic aging. Longitudinally, mLOY was associated with faster FEV1 decline (∼55mL/year vs ∼38mL/year). Prospectively, mLOY was associated with higher odds of developing COPD [OR = 1.84, 95% CI, 1.10-3.07] and preserved ratio impaired spirometry (PRISm) [OR = 2.87, 95% CI, 1.09-7.56] among participants with normal lung function at baseline. Associations remained robust after adjusting for clonal hematopoiesis and telomere length.

conclusionsmLOY is associated with lower lung function, accelerated lung function decline, higher emphysema, and faster pace of aging, positioning mLOY as a potential biomarker of respiratory aging in men.

Indexed as

AgingChromosomes, Human, YEpigenesis, GeneticMosaicismPulmonary Disease, Chronic ObstructivePulmonary EmphysemaAgedCross-Sectional StudiesHumansMaleMiddle AgedProspective StudiesRespiratory Function TestsSpirometryagingCOPDemphysemaspirometryY chromosome

Identifiers

PMID42085243
PMCPMC13322295

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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.