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Common DNA sequence variation influences epigenetic aging in African populations.

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|November 5, 2025
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Summary

Epigenetic age prediction models show higher errors in understudied populations due to DNA sequence variation. A new model accounting for methylation quantitative trait loci (meQTL) improves accuracy across diverse genetic backgrounds, revealing heritable factors influence longevity.

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Area of Science:

  • Genetics
  • Epigenetics
  • Population Health

Background:

  • Aging causes genome-wide DNA methylation changes, enabling epigenetic age prediction.
  • Current epigenetic age models are biased towards European-ancestry individuals and do not account for methylation quantitative trait loci (meQTL).

Purpose of the Study:

  • To assess epigenetic age prediction accuracy in understudied African populations.
  • To develop a more accurate epigenetic age predictor by accounting for meQTL effects across diverse genetic backgrounds.
  • To investigate the relationship between genetic variants, epigenetic age, and longevity.

Main Methods:

  • Analysis of DNA methylation and genotype data in Baka, ‡Khomani San, and Himba populations.
  • Comparison of existing epigenetic age predictors' performance in these cohorts versus European-ancestry individuals.
  • Development of a novel age predictor model incorporating meQTL information.

Main Results:

  • Published epigenetic age predictors exhibited higher mean errors in the studied African populations compared to European-ancestry individuals.
  • Unaccounted DNA sequence variation significantly impacts predictor accuracy.
  • The novel meQTL-aware model demonstrated consistent accuracy across diverse genetic backgrounds.
  • Older individuals and those with lower epigenetic age acceleration possessed more genetic variants associated with reduced epigenetic age.

Conclusions:

  • Epigenetic age prediction requires models robust to diverse genetic backgrounds.
  • Heritable genetic factors collectively influence human healthspan and longevity.
  • Accounting for meQTL is crucial for accurate and equitable epigenetic age prediction across populations.