BACKGROUND: Mosaic loss of the Y chromosome (mLoY) is the most common age-related somatic mutation in male humans and has been associated with increased mortality and fibrotic cardiovascular phenotypes. OBJECTIVES: This study aimed to evaluate the associations among mLoY, atrial fibrillation (AF), and mortality in a large hospital-based biobank cohort. METHODS: We analyzed 17,916 male participants aged ≥20 years from the Mass General Brigham Biobank with available genomic and clinical data. mLoY was quantified using mean log R ratio of the Y chromosome values derived from genotyping array data. Two classification approaches were used: histogram-based cutoffs and a mean log R ratio of the Y chromosome-based threshold method. Associations among mLoY, AF, and mortality were evaluated using multivariable logistic regression, adjusting for cardiovascular comorbidities. RESULTS: Among 2,940 AF patients and 14,976 control participants, mLoY prevalence was higher in AF patients across both classification methods. After adjusting for age and comorbidities, individuals with Y chromosome value <-0.1 had a 25% increased odds of AF (adjusted OR: 1.25; 95% CI: 1.01-1.55). Among patients with AF, mLoY was independently associated with a 37% higher risk of all-cause mortality (adjusted OR: 1.37; 95% CI: 1.06-1.79). CONCLUSIONS: mLoY is independently associated with a higher prevalence of AF and higher mortality among AF patients. These findings support mLoY as a potential biomarker for cardiovascular risk stratification in aging men and highlight fibrosis as a key mechanistic pathway warranting further investigation.
Sanadgol et al. (Mon,) studied this question.