Genetic predisposition to mosaic Y chromosome loss in blood

Deborah J Thompson, Giulio Genovese, Siddhartha Kar, John RB Perry*, et al.

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1,2,3,4,5, 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.
Original languageEnglish
Pages (from-to)652–657
Number of pages6
Early online date20 Nov 2019
Publication statusPublished - 28 Nov 2019


  • Cancer genomics
  • Cell division
  • Genome-wide association studies
  • Genomic instability
  • Haematopoietic system


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