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
This is a preview of subscription content, log in to check access.
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.
Aviv A, Chen W, Gardner JP, et al. Leukocyte telomere dynamics: longitudinal findings among young adults in the Bogalusa heart study. Am J Epidemiol. 2009;169:323–9.PubMedCrossRefGoogle Scholar
Ehrlenbach S, Willeit P, Kiechl S, et al. Influences on the reduction of relative telomere length over 10 years in the population-based Bruneck Study: introduction of a well-controlled high-throughput assay. Int J Epidemiol. 2009;38(6):1725–34. doi:10.1093/ije/dyp273.PubMedCrossRefGoogle Scholar
Farzaneh-Far R, Lin J, Epel E, Lapham K, Blackburn E, Whooley MA. Telomere length trajectory and its determinants in persons with coronary artery disease: longitudinal findings from the heart and soul study. PLoS One. 2010;5(1):e8612. doi:10.1371/journal.pone.0008612.PubMedCrossRefGoogle Scholar
R_Core_Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2012.Google Scholar
Aviv A, Hunt SC, Lin J, Cao XJ, Kimura M, Blackburn E. Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR. Nucl Acids Res. 2011;39(20):e134. doi:10.1093/nar/gkr634.PubMedCrossRefGoogle Scholar
Benetos A, Okuda K, Lajemi M, et al. Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity. Hypertension. 2001;37(2):381–5.PubMedCrossRefGoogle Scholar
Chen W, Kimura M, Kim S, et al. Longitudinal versus cross-sectional evaluations of leukocyte telomere length dynamics: age-dependent telomere shortening is the rule. J Gerontol A Biol Sci Med Sci. 2011;66(3):312–9. doi:10.1093/gerona/glq223.PubMedCrossRefGoogle Scholar