Cardiogenetics

Y Chromosome Loss and MI Risk

We already know that loss or mutation in genes can lead to increased cardiovascular risk or even cause some diseases, but what about losing a whole chromosome? New research in JACC suggests that men who lose pieces of their Y chromosome as they age could be at greater risk of heart attacks.

  • Every male cell (except red blood cells) includes one Y and one X chromosome as well as 44 other chromosomes.
  • In the context of this study, researchers focused on the loss of Y chromosome (LOY) specifically in leukocytes (the white blood cells in our immune system).
  • LOY in leukocytes occurs in approximately 20% of men over age 50, and nearly 40% in men over 70, with environmental factors like smoking and air pollution playing a big role.

Researchers measured the percentage loss of Y chromosome in 5.1k men over 65 who were previously enrolled in the ASPREE trial with no prior CVD, and examined how often MACE occurred during the trial’s 8.4 year follow-up, finding that…

  • Nearly 10% of men experienced MACE, with 5% being MI and 4% ischemic stroke. 
  • Each standard deviation increase in LOY was associated with 14% higher MI risk.
  • Men with the top 10% of LOY had 68% higher MI risk versus men without LOY.
  • However, LOY wasn’t associated with ischemic stroke.

Keeping an eye on LOY has already emerged as a blood-based genomic biomarker for disease risk and mortality during aging, and while the study supports this, there are a few key details it doesn’t tell us.

  • The study lacked any functional data, like cell sorting, blood cell counts, or single-cell data, which would help uncover the cell-specific patterns of LOY and underlying mechanisms.
  • Participants with LOY measurements also tended to be healthier than the overall ASPREE male population. 
  • Additionally, the study’s participants were mostly of European ancestry, limiting the generalizability of the findings to other ethnicities.

The Takeaway

This study tells us one thing very clearly – the more a man loses from his Y chromosome, the higher his risk of MI. Why this is still isn’t clear and needs further research, but it does add nuance to the risks men face as they age.

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