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A polygenic risk score predicts mosaic loss of chromosome Y in circulating blood cells

By Moeen Riaz, Jonas Mattison, Galina Polekhina, Andrew Bakshi, Jonatan Halvardson, Marcus Danielsson, Adam Ameur, John McNeil, Lars Forsberg, Paul Lacaze

Posted 22 Jun 2021
medRxiv DOI: 10.1101/2021.06.15.21258995

Mosaic loss of Y chromosome (LOY) in leukocytes is associated with risk for death and disease in men. We investigated a polygenic risk score (PRS) for LOY comprising 156 previously associated germline variants, in 5131 men aged [≥]70 years. 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 1.74). Men in the highest quintile of the PRS distribution had >5-fold higher risk of LOY than the lowest. A PRS for LOY could become a useful tool for risk prediction and targeted intervention.

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