Journal article
Mosaic Loss of Y chromosome associates with lung function, emphysema and epigenetic aging
American journal of respiratory and critical care medicine
03/19/2026
DOI: 10.1093/ajrccm/aamag120
Abstract
Rationale
As 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.
Objectives
To examine the association between mLOY and pulmonary outcomes in men.
Methods
Leveraging mLOY assessment (cell fraction ≥ 5%) in over 12,000 men, including 5,097 from the COPDGene Study and 7,235 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.
Results
The 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, -0.006] in COPDGene and 0.020 [95% CI -0.027, -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 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.
Conclusions
mLOY 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.
Details
- Title: Subtitle
- Mosaic Loss of Y chromosome associates with lung function, emphysema and epigenetic aging
- Creators
- Woei-Yuh Saw - Brigham and Women's HospitalKangjin Kim - Brigham and Women's HospitalYichen Huang - Brigham and Women's HospitalJeong H Yun - Brigham and Women's HospitalXiaolong Ma - Medical College of WisconsinJason Bacon - University of Wisconsin–MilwaukeeYash Pershad - Vanderbilt University Medical CenterDaniel Levy - National Heart Lung and Blood InstituteGeorge T O’ConnorEric Boerwinkle - The University of Texas Health Science Center at HoustonR Graham Barr - Columbia University Irving Medical CenterStephen S Rich - University of VirginiaJerome I Rotter - Ronald Reagan UCLA Medical CenterApril P Carson - University of Mississippi Medical CenterLaura M Raffield - University of North Carolina at Chapel HillSina A Gharib - University of WashingtonTraci M Bartz - University of WashingtonBruce M Psaty - University of WashingtonTamar Sofer - Beth Israel Deaconess Medical CenterKari E North - University of North Carolina at Chapel HillRobert Kaplan - Albert Einstein College of MedicineElizabeth C Oelsner - Columbia University Irving Medical CenterAni Manichaikul - University of VirginiaAlexander G Bick - Vanderbilt University Medical CenterPaul Scheet - The University of Texas MD Anderson Cancer CenterAlexander P Reiner - University of WashingtonGonçalo AbecasisFrancois AguetChristine AlbertLaura AlmasyAlvaro AlonsoSeth AmentPeter AndersonPramod AnuguKristin ArdlieDan ArkingDonna K ArnettAllison Ashley-KochStella AslibekyanTim AssimesPaul Auer - Medical College of WisconsinDimitrios AvramopoulosNajib AyasJohn BarnardKathleen BarnesR Graham Barr - Columbia University Irving Medical CenterEmily Barron-CasellaTerri BeatyGerald BeckDiane BeckerLewis BeckerAmber BeitelsheesMarcos BezerraLarry BielakJoshua BisJohn BlangeroNathan BlueDonald W BowdenRussell BowlerJennifer BrodyUlrich BroeckelDeborah BrownEsteban BurchardCarlos BustamanteBrian CadeJonathan CardwellVincent CareyCara CartyRichard CasaburiJames CasellaPeter CastaldiMark ChaffinChristy ChangYi-Cheng ChangDaniel ChasmanWei-Min ChenYii-Der Ida ChenSeung Hoan ChoiLee-Ming ChuangMina ChungRen-Hua ChungClary ClishSuzy ComhairMatthew ConomosElaine CornellCarolyn CrandallJames CrapoL Adrienne CupplesJoanne CurranJeffrey CurtisBrian CusterColeen DamcottDawood DarbarColleen DavisMichelle DayaMariza de AndradeLisa de las FuentesPaul de VriesMichael DeBaunRanjan DekaDawn DeMeo - Brigham and Women's HospitalScott DevineHarsha DoddapaneniQing DuanShannon Dugan-PerezRavi DuggiralaJon Peter DurdaSusan K DutcherCharles EatonLynette EkunweAdel El BoueizPatrick EllinorSerpil ErzurumCharles FarberTasha FingerlinMyriam FornageNora FranceschiniChris FrazarMao FuStephanie M FullertonLucinda FultonStacey GabrielWeiniu GanShanshan GaoMargery GassHeather GeigerBruce GelbMark GeraciSoren GermerRobert GersztenAuyon GhoshRichard GibbsMark GladwinDavid GlahnStephanie GogartenHarald GoringSharon GrawKathryn J GrayC Charles GuXiuqing GuoNamrata GuptaJeff HaesslerMichael HallPatrick HanlyDaniel HarrisNicola L HawleyJiang HeBen HeavnerRyan HernandezDavid HerringtonCraig HershBertha HidalgoJames HixsonBrian HobbsJohn HokansonKarin HothChao (Agnes) HsiungChii Min HwuMarguerite Ryan IrvinCashell JaquishJill JohnsenAndrew JohnsonCraig JohnsonRich JohnstonKimberly JonesSharon KardiaShannon KellyEimear KennyMichael KesslerAlyna KhanWonji KimGreg KinneyBarbara KonkleCharles KooperbergHolly KramerChristoph LangeEthan LangeCathy LaurieMeryl LeBoffWen-Jane LeeJonathon LeFaiveDan Levy - National Heart Lung and Blood InstituteJoshua LewisXiaohui LiYun LiHenry LinHonghuang LinXihong LinSimin LiuYongmei LiuYu LiuRuth J F LoosSteven LubitzKathryn LunettaJames LuoUlysses MagalangMichael MahaneyBarry MakeAlisa ManningJoAnn MansonLisa MartinMelissa MartonSusan MathaiRasika MathiasPatrick McArdleMerry-Lynn McDonaldBecky McNeilHao MeiJames MeigsLuisa MestroniGinger MetcalfDeborah A MeyersEmmanuel MignotJulie MikullaYuan-I MinRyan L MinsterBraxton D MitchellMatt MollMay MontasserCourtney MontgomeryDonna MuznyJosyf C MychaleckyjGirish NadkarniRakhi NaikPradeep NatarajanSergei NekhaiKari North - University of North Carolina at Chapel HillJeff O'ConnellTim O'ConnorHeather Ochs-BalcomAllan PackNicholette PalmerJames PankowGina PelosoJuan Manuel PeraltaMarco PerezJames PerryUlrike PetersPatricia PeyserLawrence S PhillipsToni PollinWendy PostJulia Powers BeckerMeher Preethi BoorgulaMichael PreussBruce Psaty - University of WashingtonPankaj QasbaDandi QiaoZhaohui QinNicholas RafaelsLaura Raffield - University of North Carolina at Chapel HillD C RaoLaura Rasmussen-TorvikAakrosh RatanSusan RedlineRobert ReedCatherine ReevesElizabeth ReganAlex Reiner - University of WashingtonRebecca RobillardNicolas RobineDan RodenCarolina RoselliJerome Rotter - Ronald Reagan UCLA Medical CenterIngo RuczinskiAlexi RunnelsSarah RuuskaKathleen RyanEster Cerdeira SabinoDanish SaleheenShabnam SalimiSteven SalzbergKevin SandowVijay G SankaranRicha SaxenaKaren SchwanderDavid SchwartzFrank SciurbaChristine SeidmanJonathan SeidmanVivien SheehanStephanie L ShermanAmol ShettyWayne Hui-Heng SheuM Benjamin ShoemakerBrian SilverAlbert Vernon SmithJennifer SmithJosh SmithNicholas SmithSylvia SmollerMichael SnyderNona SotoodehniaAdrienne M StilpGarrett StormElizabeth StreetenJessica Lasky SuYun Ju SungAdam SzpiroHua TangMargaret TaubKent D TaylorMatthew TaylorSimeon TaylorMarilyn TelenTimothy A ThorntonMachiko ThrelkeldLesley TinkerDavid TirschwellSarah TishkoffHemant TiwariCatherine TongRussell TracyMichael TsaiDhananjay VaidyaDavid Van Den BergScott VriezeTarik WalkerRobert WallaceHeming WangJiongming WangKarol WatsonDaniel E WeeksJoshua WeinstockLu-Chen WengJennifer WesselL Keoki WilliamsScott WilliamsCarla WilsonLara WinterkornBaojun WuJoseph WuHuichun XuLisa YanekIvana YangRonit YardenSeyedeh Maryam ZekavatYingze ZhangWei ZhaoXiaofeng ZhuElad ZivMichael ZodyYasminka A Jakubek - University of KentuckyPaul L Auer - Medical College of WisconsinMichael H Cho - Harvard UniversityNHLBI Trans-Omics for Precision Medicine Consortium
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine
- DOI
- 10.1093/ajrccm/aamag120
- ISSN
- 1535-4970
- eISSN
- 1535-4970
- Publisher
- Oxford University Press
- Language
- English
- Electronic publication date
- 03/19/2026
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9985149414302771
Metrics
1 Record Views