학술논문
A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells
Document Type
article
Author
Source
Cell & Bioscience, Vol 11, Iss 1, Pp 1-8 (2021)
Subject
Language
English
ISSN
2045-3701
Abstract
Abstract Background Mosaic loss of Y chromosome (LOY) is the most common somatic change that occurs in circulating white blood cells of older men. LOY in leukocytes is associated with increased risk for all-cause mortality and a range of common disease such as hematological and non-hematological cancer, Alzheimer’s disease, and cardiovascular events. Recent genome-wide association studies identified up to 156 germline variants associated with risk of LOY. The objective of this study was to use these variants to calculate a novel polygenic risk score (PRS) for LOY, and to assess the predictive performance of this score in a large independent population of older men. Results We calculated a PRS for LOY in 5131 men aged 70 years and older. Levels of LOY were estimated using microarrays and validated by whole genome sequencing. After adjusting for covariates, the PRS was a significant predictor of LOY (odds ratio [OR] = 1.74 per standard deviation of the PRS, 95% confidence intervals [CI] 1.62–1.86, p fivefold higher risk of LOY than the lowest (OR = 5.05, 95% CI 4.05–6.32, p