American journal of respiratory and critical care medicine · 2026
Mosaic loss of Y chromosome associates with lung function, emphysema, and epigenetic aging.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Saw Woei-Yuh, Kim Kangjin, Huang Yichen, Yun Jeong H, Ma Xiaolong, Bacon Jason, Pershad Yash, Levy Daniel, O'Connor George T, Boerwinkle Eric, Barr R Graham, Rich Stephen S, Rotter Jerome I, Carson April P, Raffield Laura M, Gharib Sina A, Bartz Traci M, Psaty Bruce M, Sofer Tamar, North Kari E, Kaplan Robert C, Oelsner Elizabeth C, Manichaikul Ani, Bick Alexander G, Scheet Paul, Reiner Alexander P, NHLBI Trans-Omics for Precision Medicine Consortium, Jakubek Yasminka A, Auer Paul L, Cho Michael H, DeMeo Dawn L
Аннотация
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 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.
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 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.
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.
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 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.
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 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.
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.