A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells.
ASPREE
LOY
Mosaic loss of chromosome Y
PRS
Polygenic risk score
mLOY
Journal
Cell & bioscience
ISSN: 2045-3701
Titre abrégé: Cell Biosci
Pays: England
ID NLM: 101561195
Informations de publication
Date de publication:
12 Dec 2021
12 Dec 2021
Historique:
received:
16
09
2021
accepted:
19
11
2021
entrez:
13
12
2021
pubmed:
14
12
2021
medline:
14
12
2021
Statut:
epublish
Résumé
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. 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 < 0.001). Men in the highest quintile of the PRS distribution had > fivefold higher risk of LOY than the lowest (OR = 5.05, 95% CI 4.05-6.32, p < 0.001). Adding the PRS to a LOY prediction model comprised of age, smoking and alcohol consumption significantly improved prediction (AUC = 0.628 [CI 0.61-0.64] to 0.695 [CI 0.67-0.71], p < 0.001). Our results suggest that a PRS for LOY could become a useful tool for risk prediction and targeted intervention for common disease in men.
Sections du résumé
BACKGROUND
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
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 < 0.001). Men in the highest quintile of the PRS distribution had > fivefold higher risk of LOY than the lowest (OR = 5.05, 95% CI 4.05-6.32, p < 0.001). Adding the PRS to a LOY prediction model comprised of age, smoking and alcohol consumption significantly improved prediction (AUC = 0.628 [CI 0.61-0.64] to 0.695 [CI 0.67-0.71], p < 0.001).
CONCLUSIONS
CONCLUSIONS
Our results suggest that a PRS for LOY could become a useful tool for risk prediction and targeted intervention for common disease in men.
Identifiants
pubmed: 34895331
doi: 10.1186/s13578-021-00716-z
pii: 10.1186/s13578-021-00716-z
pmc: PMC8667399
doi:
Types de publication
Journal Article
Langues
eng
Pagination
205Informations de copyright
© 2021. The Author(s).
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