Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men

Abstract Mosaic loss of Y chromosome (mLOY) is the most frequently detected somatic copy number alteration in leukocytes of men. In this study, we investigate blood cell counts as a potential mechanism linking mLOY to disease risk in 206,353 UK males. Associations between mLOY, detected by genotypin...

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Autores principales:	Shu-Hong Lin, Erikka Loftfield, Josh N. Sampson, Weiyin Zhou, Meredith Yeager, Neal D. Freedman, Stephen J. Chanock, Mitchell J. Machiela
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3657fd93f594486e8c3cc7036ed61d27
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spelling	oai:doaj.org-article:3657fd93f594486e8c3cc7036ed61d272021-12-02T15:53:47ZMosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men10.1038/s41598-020-59963-82045-2322https://doaj.org/article/3657fd93f594486e8c3cc7036ed61d272020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-59963-8https://doaj.org/toc/2045-2322Abstract Mosaic loss of Y chromosome (mLOY) is the most frequently detected somatic copy number alteration in leukocytes of men. In this study, we investigate blood cell counts as a potential mechanism linking mLOY to disease risk in 206,353 UK males. Associations between mLOY, detected by genotyping arrays, and blood cell counts were assessed by multivariable linear models adjusted for relevant risk factors. Among the participants, mLOY was detected in 39,809 men. We observed associations between mLOY and reduced erythrocyte count (−0.009 [−0.014, −0.005] × 1012 cells/L, p = 2.75 × 10−5) and elevated thrombocyte count (5.523 [4.862, 6.183] × 109 cells/L, p = 2.32 × 10−60) and leukocyte count (0.218 [0.198, 0.239] × 109 cells/L, p = 9.22 × 10−95), particularly for neutrophil count (0.174 × [0.158, 0.190]109 cells/L, p = 1.24 × 10−99) and monocyte count (0.021 [0.018 to 0.024] × 109 cells/L, p = 6.93 × 10−57), but lymphocyte count was less consistent (0.016 [0.007, 0.025] × 109 cells/L, p = 8.52 × 10−4). Stratified analyses indicate these associations are independent of the effects of aging and smoking. Our findings provide population-based evidence for associations between mLOY and blood cell counts that should stimulate investigation of the underlying biological mechanisms linking mLOY to cancer and chronic disease risk.Shu-Hong LinErikka LoftfieldJosh N. SampsonWeiyin ZhouMeredith YeagerNeal D. FreedmanStephen J. ChanockMitchell J. MachielaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shu-Hong Lin Erikka Loftfield Josh N. Sampson Weiyin Zhou Meredith Yeager Neal D. Freedman Stephen J. Chanock Mitchell J. Machiela Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men
description	Abstract Mosaic loss of Y chromosome (mLOY) is the most frequently detected somatic copy number alteration in leukocytes of men. In this study, we investigate blood cell counts as a potential mechanism linking mLOY to disease risk in 206,353 UK males. Associations between mLOY, detected by genotyping arrays, and blood cell counts were assessed by multivariable linear models adjusted for relevant risk factors. Among the participants, mLOY was detected in 39,809 men. We observed associations between mLOY and reduced erythrocyte count (−0.009 [−0.014, −0.005] × 1012 cells/L, p = 2.75 × 10−5) and elevated thrombocyte count (5.523 [4.862, 6.183] × 109 cells/L, p = 2.32 × 10−60) and leukocyte count (0.218 [0.198, 0.239] × 109 cells/L, p = 9.22 × 10−95), particularly for neutrophil count (0.174 × [0.158, 0.190]109 cells/L, p = 1.24 × 10−99) and monocyte count (0.021 [0.018 to 0.024] × 109 cells/L, p = 6.93 × 10−57), but lymphocyte count was less consistent (0.016 [0.007, 0.025] × 109 cells/L, p = 8.52 × 10−4). Stratified analyses indicate these associations are independent of the effects of aging and smoking. Our findings provide population-based evidence for associations between mLOY and blood cell counts that should stimulate investigation of the underlying biological mechanisms linking mLOY to cancer and chronic disease risk.
format	article
author	Shu-Hong Lin Erikka Loftfield Josh N. Sampson Weiyin Zhou Meredith Yeager Neal D. Freedman Stephen J. Chanock Mitchell J. Machiela
author_facet	Shu-Hong Lin Erikka Loftfield Josh N. Sampson Weiyin Zhou Meredith Yeager Neal D. Freedman Stephen J. Chanock Mitchell J. Machiela
author_sort	Shu-Hong Lin
title	Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men
title_short	Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men
title_full	Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men
title_fullStr	Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men
title_full_unstemmed	Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men
title_sort	mosaic chromosome y loss is associated with alterations in blood cell counts in uk biobank men
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/3657fd93f594486e8c3cc7036ed61d27
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Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men

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