A 2019 study of 95,380 Japanese men found 46 genetic loci shaping how likely white blood cells are to lose their Y chromosome with age — a common, age-related mosaic change, not something present at birth.
Mosaic loss of chromosome Y (mLOY) is a phenomenon in which some of a man's white blood cells (leukocytes) progressively lose their Y chromosome as he ages — a mosaic, acquired change happening in a fraction of blood cells over a lifetime, not a fixed trait present from birth. It is one of the most common forms of clonal mosaicism detectable in blood, and it becomes more frequent with age. The germline genetic variants on this page do not cause mLOY directly; they shift how likely it is to happen and how far it progresses as a man ages.
Terao et al. 2019 studied 95,380 Japanese men and identified 50 independent genetic markers across 46 loci genome-wide-significantly associated with mLOY, 35 of them never previously reported. The lead markers overlapped enhancer regions active specifically in hematopoietic stem cells (HSCs) — the cells in bone marrow that give rise to all blood cell types — and the overall genetic signal was strongly enriched near genes expressed in HSCs and their multipotent progenitor cells.
A specific mechanistic clue emerged from this enrichment: binding sites for FLI1, a transcription factor that steers blood stem cells toward becoming platelets rather than red blood cells, showed unusually strong heritability enrichment. Consistent with that finding, higher platelet counts and lower red blood cell counts were both associated with more mLOY — tying a chromosomal mosaic event back to a specific decision point in how blood stem cells differentiate. Two of this page's variants, rs139012944 and rs728739, sit in TCL1A, a gene independently well known in hematopoietic stem cell biology and in the study of clonal blood cell expansion more broadly.
mLOY is detected by testing blood cells directly, not inferred from germline genotype, and this page's variants do not diagnose it or predict whether or when it will occur in an individual. The variants here describe a population-level genetic predisposition to a chromosomal change that happens, if it happens, later in life and in blood cells specifically — they are not present-at-birth risk markers for a fixed condition.
mLOY itself is studied in relation to blood cell counts and hematopoietic biology, as described above; it is not diagnosed or monitored using the germline variants on this page, and no clinical guideline uses this page's variants for screening or management.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Mosaic Loss of Chromosome Y comes down to these specific, well-studied positions — not a diagnosis.
LINC01565 · rs2811487
See detailed info →ANGPTL2 · rs138423884
See detailed info →LOC102724152 · rs4709819
See detailed info →LINC01478 · rs80277818
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 22 of 22 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
mLOY is a phenomenon in which some of a man's white blood cells progressively lose their Y chromosome as he ages — an acquired, mosaic change in a fraction of blood cells over a lifetime, not something present from birth.
Studying 95,380 Japanese men, it found 46 genetic loci associated with mLOY, most of them near genes active in blood stem cells. It also linked mLOY to a specific process — how stem cells decide to become platelets versus red blood cells — via enrichment near FLI1 binding sites.
No. These are population-level genetic associations with a germline predisposition, not predictions for an individual. mLOY itself is detected directly by testing blood cells, not inferred from these variants, and typically only becomes relevant later in life.
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