Published October 31, 2019 | Version Final published version
Journal article Open

Controlling for baseline telomere length biases estimates of the rate of telomere attrition.

  • 1. Newcastle University
  • 2. University of Washington


Published article, Supplementary Material, associated R script and dataset.



Longitudinal studies have sought to establish whether environmental exposures such as smoking accelerate the attrition of individuals’ telomeres over time. These studies typically control for baseline telomere length (TL) by including it as a covariate in statistical models. However, baseline TL also differs between smokers and non-smokers, and telomere attrition is spuriously linked to baseline TL via measurement error and regression to the mean. Using simulated datasets, we show that controlling for baseline TL overestimates the true effect of smoking on telomere attrition. This bias increases with increasing telomere measurement error and increasing difference in baseline TL between smokers and non-smokers. Using a meta-analysis of longitudinal datasets, we show that as predicted, the estimated difference in telomere attrition between smokers and non-smokers is greater when statistical models control for baseline TL than when they do not, and the size of the discrepancy is positively correlated with measurement error. The bias we describe is not specific to smoking and also applies to other exposures. We conclude that to avoid invalid inference, models of telomere attrition should not control for baseline TL by including it as a covariate. Many claims of accelerated telomere attrition in individuals exposed to adversity need to be re-assessed.


Bateson Eisenberg & Nettle Supplementary Material.pdf

Files (3.4 MB)

Name Size Download all
59.0 kB Download
2.0 MB Preview Download
1.3 MB Preview Download
20.6 kB Preview Download

Additional details


COMSTAR – The effects of early-life adversity on cognition: A comparative approach. 666669
European Commission