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A polygenic risk sc...
A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells
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- Riaz, Moeen (författare)
- Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
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- Mattisson, Jonas (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab,Forsberg
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- Polekhina, Galina (författare)
- Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
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- Bakshi, Andrew (författare)
- Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
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- Halvardson, Jonatan, 1982- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Forsberg
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- Danielsson, Marcus (författare)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab,Forsberg
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- Ameur, Adam (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- McNeil, John (författare)
- Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
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- Forsberg, Lars A., 1974- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Forsberg
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- Lacaze, Paul (författare)
- Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia.
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Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Medicinsk genetik och genomik (creator_code:org_t)
- 2021-12-12
- 2021
- Engelska.
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Ingår i: Cell & Bioscience. - : Springer Nature. - 2045-3701. ; 11
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://cellandbiosc...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 < 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: Our results suggest that a PRS for LOY could become a useful tool for risk prediction and targeted intervention for common disease in men.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- General Biochemistry
- Genetics and Molecular Biology
- Mosaic loss of chromosome Y
- LOY
- mLOY
- Polygenic risk score
- PRS
- ASPREE
- Medical Genetics
- Medicinsk genetik
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Riaz, Moeen
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Mattisson, Jonas
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Polekhina, Galin ...
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Bakshi, Andrew
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Halvardson, Jona ...
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Danielsson, Marc ...
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Ameur, Adam
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McNeil, John
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Forsberg, Lars A ...
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Lacaze, Paul
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