European Journal of Epidemiology

, Volume 28, Issue 11, pp 859–866 | Cite as

Do leukocyte telomere length dynamics depend on baseline telomere length? An analysis that corrects for ‘regression to the mean’

  • Simon Verhulst
  • Abraham Aviv
  • Athanase Benetos
  • Gerald S. Berenson
  • Jeremy D. Kark


Leukocyte telomere length (LTL) shortens with age. Longitudinal studies have reported accelerated LTL attrition when baseline LTL is longer. However, the dependency of LTL attrition on baseline LTL might stem from a statistical artifact known as regression to the mean (RTM). To our knowledge no published study of LTL dynamics (LTL and its attrition rate) has corrected for this phenomenon. We illustrate the RTM effect using replicate LTL measurements, and show, using simulated data, how the RTM effect increases with a rise in stochastic measurement variation (representing LTL measurement error), resulting in spurious increasingly elevated dependencies of attrition on baseline values. In addition, we re-analyzed longitudinal LTL data collected from four study populations to test the hypothesis that LTL attrition depends on baseline LTL. We observed that the rate of LTL attrition was proportional to baseline LTL, but correction for the RTM effect reduced the slope of the relationship by 57 % when measurement error was low (coefficient of variation ~2 %). A modest but statistically significant effect remained however, indicating that high baseline LTL is associated with higher LTL attrition even when correcting for the RTM effect. Baseline LTL explained 1.3 % of the variation in LTL attrition, but this effect, which differed significantly between the study samples, appeared to be primarily attributable to the association in men (3.7 %).


Leukocyte telomere length Sex Age ‘Regression to the mean’ Longitudinal studies 



We thank an anonymous reviewer whose comments improved the manuscript. The Jerusalem LRC study was supported by grants from the Israel Science Foundation (ISF) and the US–Israel Binational Science Foundation (BSF). This work was supported in part by National Institutes of Health grants AG16592, AG030678, R01-HD071180.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Simon Verhulst
    • 1
  • Abraham Aviv
    • 2
  • Athanase Benetos
    • 3
  • Gerald S. Berenson
    • 4
  • Jeremy D. Kark
    • 5
  1. 1.Centre for Behaviour and NeurosciencesUniversity of GroningenGroningenThe Netherlands
  2. 2.The Center of Human Development and Aging, RoomUniversity of Medicine and Dentistry of New Jersey, New Jersey Medical SchoolNewarkUSA
  3. 3.Department of GeriatricsCHU Nancy, Hôpital BraboisVandoeuvre-lès-NancyFrance
  4. 4.Tulane Center for Cardiovascular HealthTulane University Health Sciences CenterNew OrleansUSA
  5. 5.Hadassah School of Public Health and Community MedicineThe Hebrew UniversityJerusalemIsrael

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