Assessment of Leukocyte Telomere Length as an Indicator of Biological Age for Risk Stratification of Cardiovascular Events: A Meta-Analysis

ABSTRACTLeukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., “direct” inheritance). Prior studies of LTL h2have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5,069 Bangladeshi adults with substantial relatedness. For each of the 7,254 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tsharedand the squared pairwise difference in LTL ((ΔLTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (ϕ). The association between Tsharedand (ΔLTL)2was inverse among all relative pair types. In a meta-analysis including all relative pairs (ϕ >0.05), the association between Tsharedand (ΔLTL)2(P=0.002) was stronger than the association between ϕ and (ΔLTL)2(P=0.45). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2despite telomere “reprogramming” during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2attributable to direction transmission.

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THE ASSOCIATION BETWEEN DEPRESSION AND LEUKOCYTE TELOMERE LENGTH: A META-ANALYSIS

Depression and Anxiety ◽

10.1002/da.22351 ◽

2015 ◽

Vol 32 (4) ◽

pp. 229-238 ◽

Cited By ~ 70

Author(s):

Nicola S. Schutte ◽

John M. Malouff

Keyword(s):

Telomere Length ◽

Meta Analysis ◽

Leukocyte Telomere Length

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Can leukocyte telomere length (LTL) be considered as an index in application of neural network in the atherosclerosis risk stratification?

International Journal of Cardiology ◽

10.1016/j.ijcard.2008.12.120 ◽

2010 ◽

Vol 144 (1) ◽

pp. 136-137 ◽

Cited By ~ 1

Author(s):

Mohaddeseh Behjati ◽

Mohammad Hashemi ◽

Mansoor Salehi ◽

Roya Kelishadi

Keyword(s):

Neural Network ◽

Risk Stratification ◽

Telomere Length ◽

Leukocyte Telomere Length ◽

Atherosclerosis Risk

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Leukocyte telomere length and hippocampus volume: a meta-analysis

F1000Research ◽

10.12688/f1000research.7198.1 ◽

2015 ◽

Vol 4 ◽

pp. 1073 ◽

Cited By ~ 14

Author(s):

Gustav Nilsonne ◽

Sandra Tamm ◽

Kristoffer N. T. Månsson ◽

Torbjörn Åkerstedt ◽

Mats Lekander

Keyword(s):

Telomere Length ◽

Meta Analysis ◽

Gray Matter Volume ◽

Apoe Genotype ◽

Telomerase Activity ◽

Brain Parenchyma ◽

Leukocyte Telomere Length ◽

The One ◽

The Relationship ◽

Hippocampus Volume

Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE) genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.

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Leukocyte telomere length, genetically determined, is causally associated with the progression of carotid Intima-Media Thickness and incidence of cardiovascular events

Atherosclerosis ◽

10.1016/j.atherosclerosis.2016.07.064 ◽

2016 ◽

Vol 252 ◽

pp. e252 ◽

Cited By ~ 1

Author(s):

A. Baragetti ◽

J. Palmen ◽

K. Garlaschelli ◽

L. Grigore ◽

S. Humphries ◽

...

Keyword(s):

Telomere Length ◽

Cardiovascular Events ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Leukocyte Telomere Length ◽

Media Thickness ◽

Genetically Determined

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A major population resource of 474,074 participants in UK Biobank to investigate determinants and biomedical consequences of leukocyte telomere length.

10.1101/2021.03.18.21253457 ◽

2021 ◽

Author(s):

Veryan Codd ◽

Matthew Denniff ◽

Chloe Swinfield ◽

Sophie C Warner ◽

Manolo Papakonstantinou ◽

...

Keyword(s):

Cell Count ◽

Telomere Length ◽

White Cell Count ◽

White Cell ◽

Biological Age ◽

Paternal Age ◽

Leukocyte Telomere Length ◽

Uk Biobank ◽

Paired Samples

The determinants and biomedical consequences of variation in leukocyte telomere length (LTL), a proposed marker of biological age, are only partially understood. Here we report the creation and initial characterization of LTL measurements in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in "biological age" than men. Compared to white Europeans, LTL is longer in African, Chinese and other major ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes have weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1351 participants taken ~5 years apart, we show the regression-dilution ratio for LTL is ~0.65. This novel resource provides major opportunities to investigate LTL and multiple biomedical phenotypes.

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Differences in Leukocyte Telomere Length between Coronary Heart Disease and Normal Population: A Multipopulation Meta-Analysis

BioMed Research International ◽

10.1155/2019/5046867 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Xiaofeng Xu ◽

Haochang Hu ◽

Ying Lin ◽

Fangzhong Huang ◽

Huihui Ji ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Telomere Length ◽

Design Method ◽

Normal Population ◽

Meta Analysis ◽

Cardiovascular Death ◽

Leukocyte Telomere Length ◽

Asian Patients ◽

Common Causes

Coronary heart disease (CHD) is one of the most common causes of death in the world. Numerous studies have shown that as the degree of atherosclerotic disease increases, leukocyte telomere length gradually decreases. Short telomeres increase the risk of all-cause death and cardiovascular death. However, the reported results are not consistent, since the experimental design method, the measurement method, and the disease outcome are different. Therefore, we searched five major literature databases (Pubmed, Web of science, Embase, CNKI, and Wangfang) and finally included 18 eligible articles (including 5,150 patients with CHD and 9341 controls). We found that telomere length in patients with CHD was significantly shorter than that in controls, and the telomere length was inversely correlated with the severity of CHD. Subgroup analysis showed that telomere shortening was the most significant in Asian patients with CHD, in CHD patients with an average age <65 years, and in men with CHD. The mechanism of shortening the telomere length leading to the occurrence and development of CHD is worthy of further study.

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