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Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa

Telomere shortening has emerged as an important biomarker of aging. Longitudinal studies consistently find that, although telomere length shortens over time on average, there is a subset of individuals for whom telomere length is observed to increase. This apparent lengthening could either be a genu...

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Autores principales: Nettle, Daniel, Bateson, Melissa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410151/
https://www.ncbi.nlm.nih.gov/pubmed/28462056
http://dx.doi.org/10.7717/peerj.3265
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author Nettle, Daniel
Bateson, Melissa
author_facet Nettle, Daniel
Bateson, Melissa
author_sort Nettle, Daniel
collection PubMed
description Telomere shortening has emerged as an important biomarker of aging. Longitudinal studies consistently find that, although telomere length shortens over time on average, there is a subset of individuals for whom telomere length is observed to increase. This apparent lengthening could either be a genuine biological phenomenon, or simply due to measurement and sampling error. Simons, Stulp & Nakagawa (2014) recently proposed a statistical test for detecting when the amount of apparent lengthening in a dataset exceeds that which should be expected due to error, and thus indicating that genuine elongation may be operative in some individuals. However, the test is based on a restrictive assumption, namely that each individual’s true rate of telomere change is constant over time. It is not currently known whether this assumption is true. Here we show, using simulated datasets, that with perfect measurement and large sample size, the test has high power to detect true lengthening as long as the true rate of change is either constant, or moderately stable, over time. If the true rate of change varies randomly from year to year, the test systematically returns type-II errors (false negatives; that is, failures to detect lengthening even when a substantial fraction of the population truly lengthens each year). We also consider the impact of measurement error. Using estimates of the magnitude of annual attrition and of measurement error derived from the human telomere literature, we show that power of the test is likely to be low in several empirically-realistic scenarios, even in large samples. Thus, whilst a significant result of the proposed test is likely to indicate that true lengthening is present in a data set, type-II errors are a likely outcome, either if measurement error is substantial, and/or the true rate of telomere change varies substantially over time within individuals.
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spelling pubmed-54101512017-05-01 Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa Nettle, Daniel Bateson, Melissa PeerJ Genetics Telomere shortening has emerged as an important biomarker of aging. Longitudinal studies consistently find that, although telomere length shortens over time on average, there is a subset of individuals for whom telomere length is observed to increase. This apparent lengthening could either be a genuine biological phenomenon, or simply due to measurement and sampling error. Simons, Stulp & Nakagawa (2014) recently proposed a statistical test for detecting when the amount of apparent lengthening in a dataset exceeds that which should be expected due to error, and thus indicating that genuine elongation may be operative in some individuals. However, the test is based on a restrictive assumption, namely that each individual’s true rate of telomere change is constant over time. It is not currently known whether this assumption is true. Here we show, using simulated datasets, that with perfect measurement and large sample size, the test has high power to detect true lengthening as long as the true rate of change is either constant, or moderately stable, over time. If the true rate of change varies randomly from year to year, the test systematically returns type-II errors (false negatives; that is, failures to detect lengthening even when a substantial fraction of the population truly lengthens each year). We also consider the impact of measurement error. Using estimates of the magnitude of annual attrition and of measurement error derived from the human telomere literature, we show that power of the test is likely to be low in several empirically-realistic scenarios, even in large samples. Thus, whilst a significant result of the proposed test is likely to indicate that true lengthening is present in a data set, type-II errors are a likely outcome, either if measurement error is substantial, and/or the true rate of telomere change varies substantially over time within individuals. PeerJ Inc. 2017-04-27 /pmc/articles/PMC5410151/ /pubmed/28462056 http://dx.doi.org/10.7717/peerj.3265 Text en ©2017 Nettle and Bateson http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Genetics
Nettle, Daniel
Bateson, Melissa
Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa
title Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa
title_full Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa
title_fullStr Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa
title_full_unstemmed Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa
title_short Detecting telomere elongation in longitudinal datasets: analysis of a proposal by Simons, Stulp and Nakagawa
title_sort detecting telomere elongation in longitudinal datasets: analysis of a proposal by simons, stulp and nakagawa
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410151/
https://www.ncbi.nlm.nih.gov/pubmed/28462056
http://dx.doi.org/10.7717/peerj.3265
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