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

Saw, W.-Y., Kim, K., Huang, Y., Yun, J. H., Ma, X., Bacon, J., Pershad, Y., Levy, D., O'Connor, G. T., Boerwinkle, E., Barr, R. G., Rich, S. S., Rotter, J. I., Carson, A. P., Raffield, L. M., Gharib, S. A., Bartz, T. M., Psaty, B. M., Sofer, T., North, K. E., Kaplan, R., Oelsner, E. C., Manichaikul, A., Bick, A., Scheet, P., Reiner, A. P., NHLBI Trans-Omics for Precision Medicine Consortium, , Jakubek, Y., Auer, P. L., Cho, M. H., DeMeo, D. L.

Brigham and Women\'s Hospital · medrxiv

Paper

Abstract

Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mutation, but its relationship with pulmonary health remains undercharacterized. Leveraging mLOY assessment in over 12,000 men, including 5,097 from the COPDGene Study and 7,235 from six additional cohorts in Trans-Omics for Precision Medicine program, we investigated its association with respiratory outcomes and epigenetic aging. Cross-sectionally, mLOY was associated with airflow obstruction with prevalence increasing with age, particularly in men with a former smoking history. Longitudinally, mLOY associated with lung function decline. Notably, mLOY was also associated with greater CT-quantified lung emphysema and faster pace epigenetic aging. Prospectively, in participants with normal lung function at baseline, mLOY was associated with lower future lung function and faster pace of epigenetic aging. These associations remained robust after adjusting for clonal hematopoiesis and telomere length. Collectively, these findings position mLOY as a potential biomarker of respiratory aging and obstructive lung disease.

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Research summary

Mosaic loss of Y chromosome (mLOY) is associated with lung function decline and epigenetic aging in men. The study investigates a potential biomarker related to aging processes, linking genetic mutations to respiratory health and aging, which is relevant to understanding the root causes of aging.

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