Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Genetic predisposition to mosaic Y chromosome loss in blood.

Authors: Thompson, Deborah J; Genovese, Giulio; Halvardson, Jonatan; Ulirsch, Jacob C; Wright, Daniel J; Terao, Chikashi; Davidsson, Olafur B; Day, Felix R; Sulem, Patrick; Jiang, Yunxuan; Danielsson, Marcus; Davies, Hanna; Dennis, Joe; Dunlop, Malcolm G; Easton, Douglas F; Fisher, Victoria A; Zink, Florian; Houlston, Richard S; Ingelsson, Martin; Kar, Siddhartha; Kerrison, Nicola D; Kinnersley, Ben; Kristjansson, Ragnar P; Law, Philip J; Li, Rong; Loveday, Chey; Mattisson, Jonas; McCarroll, Steven A; Murakami, Yoshinori; Murray, Anna; Olszewski, Pawel; Rychlicka-Buniowska, Edyta; Scott, Robert A; Thorsteinsdottir, Unnur; Tomlinson, Ian; Moghadam, Behrooz Torabi; Turnbull, Clare; Wareham, Nicholas J; Gudbjartsson, Daniel F; International Lung Cancer Consortium (INTEGRAL-ILCCO); Breast Cancer Association Consortium; Consortium of Investigators of Modifiers of BRCA1/2; Endometrial Cancer Association Consortium; Ovarian Cancer Association Consortium; Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) Consortium; Kidney Cancer GWAS Meta-Analysis Project; eQTLGen Consortium; Biobank-based Integrative Omics Study (BIOS) Consortium; 23andMe Research Team; Kamatani, Yoichiro; Hoffmann, Eva R; Jackson, Steve P; Stefansson, Kari; Auton, Adam; Ong, Ken K; Machiela, Mitchell J; Loh, Po-Ru; Dumanski, Jan P; Chanock, Stephen J; Forsberg, Lars A; Perry, John R B

Published In Nature, (2019 11)

Abstract: Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.

PubMed ID: 31748747 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Chromosome Deletion*; Chromosomes, Human, Y/genetics*; Computational Biology; Databases, Genetic; Female; Genetic Markers/genetics; Genetic Predisposition to Disease/genetics*; Genomic Instability/genetics*; Humans; Leukocytes/pathology*; Male; Middle Aged; Mosaicism*; Neoplasms/genetics; United Kingdom

to Top