Y chromosome loss emerges in this paper not as a passive marker of ageing, but as a potentially central male-specific biological signal linked to cardiovascular death, cancer progression, neurodegeneration, and immune dysfunction across a massive evidence base. The full paper is worth reading because it shows where this signal is strongest, how consistent it is across 1,048 original studies, and why LOY may become both a prognostic biomarker and a future therapeutic target.
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Abstract: This paper aims to systematically review and synthesize the current academic understanding of Y chromosome loss, identifying its prevalence, associated pathologies, underlying mechanisms, and clinical and research implications. The review utilises 1048 original studies with 5855590 total participants (naïve ΣN). Loss of the Y chromosome (LOY) is a prevalent, age-related genomic alteration in men, profoundly influencing health outcomes across a spectrum of diseases. This systematic review highlights LOY as a significant risk factor for increased mortality, particularly from cardiovascular events, with substantial LOY associated with a 68% higher risk of myocardial infarction. It is implicated in the pathogenesis and prognosis of numerous cancers, neurodegenerative disorders, and other systemic conditions, often by modulating immune responses and cellular metabolism. While many studies are correlational, the consistent associations underscore the importance of LOY in male-specific disease biology. A key limitation is the frequent lack of long-term prospective data, necessitating future large-scale cohort studies to definitively establish causality and validate LOY as a robust prognostic and therapeutic biomarker.
Keywords: Loss of Y chromosome; Mosaic LOY; Cancer; Tumor progression; Alzheimer's disease; Clonal hematopoiesis; Cardiovascular disease; Myocardial infarction; Amyotrophic lateral sclerosis
Review Stats
Generated: 2026-02-28 01:19:24 CET
Plan: Pro (expanded craft tokens; source: Europe PMC)
Source: Europe PMC
Scope: Titles/Abstracts (tiab)
Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
Total Abstracts/Papers: 1795
Downloaded Abstracts/Papers: 1795
Included original Abstracts/Papers (all): 1422
Included original Abstracts/Papers (OSMA; excl. Mixed): 1048
Reference Index (links used in paper): 95
Total study participants (naïve ΣN): 5855590
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[31] Large-scale analysis of loss of chromosome Y in human pluripotent stem cells: Implications for Turner syndrome and ribosomopathies. — https://doi.org/10.1016/j.stemcr.2025.102471
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[193] Selective loss of Y chromosomes in lung adenocarcinoma modulates the tumor immune environment through cancer/testis antigens — https://doi.org/10.1101/2024.09.19.613876
[220] DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease. — https://doi.org/10.1007/s00018-025-05618-8
[278] Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium. — https://doi.org/10.3390/cancers16050961
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[376] Association of Y chromosome AZF region microdeletions with recurrent miscarriage in Iranian couples: A case-control study. — https://doi.org/10.1002/mgg3.2392
[408] Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. — https://doi.org/10.1038/ng.2966
