scholarly journals The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans

2018 ◽  
Author(s):  
Dayana A. Delgado ◽  
Chenan Zhang ◽  
Kathryn Demanelis ◽  
Lin S. Chen ◽  
Jianjun Gao ◽  
...  
Keyword(s):  
Telomere Length ◽  
Genetic Relatedness ◽  
Meta Analysis ◽  
Telomere Maintenance ◽  
Leukocyte Telomere Length ◽  
Relative Pair ◽  
Identity By Descent ◽  
Novel Approach ◽  
Genome Wide ◽  
Heritable Trait

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.

Leukocyte telomere length in patients with bipolar disorder: An updated meta-analysis and subgroup analysis by mood status

2018 ◽  
Vol 270 ◽  
pp. 41-49 ◽  
Author(s):  
Yu-Chi Huang ◽  
Liang-Jen Wang ◽  
Ping-Tao Tseng ◽  
Chi-Fa Hung ◽  
Pao-Yen Lin
Keyword(s):  
Bipolar Disorder ◽  
Telomere Length ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Leukocyte Telomere Length

scholarly journals Transcriptional activity of TRF2 is telomere length dependent

2016 ◽  
Author(s):  
Ananda Kishore Mukherjee ◽  
Shalu Sharma ◽  
Parashar Dhapola ◽  
Dhurjhoti Saha ◽  
Tabish Hussain ◽  
...  
Keyword(s):  
Telomere Length ◽  
Genome Stability ◽  
Telomere Maintenance ◽  
Regulatory Control ◽  
Gene Promoters ◽  
Multiple Gene ◽  
Telomere Repeat ◽  
Genome Wide ◽  
Binding Factor

AbstractTRF2 is a telomere repeat binding factor crucial for telomere maintenance and genome stability. An emerging non-conventional role of TRF2 is as a transcriptional regulator through extra-telomeric bindings. Herein we report that increase in telomere length leads to sequestration of TRF2 at the telomeres leading to reduced extra-telomeric TRF2 occupancy genome wide. Decrease in TRF2 occupancy was found on multiple gene promoters in cells with elongated telomeres, including the cell cycle regulator kinase-p21. We found that TRF2 is a transcriptional repressor of p21, and, interestingly, TRF2-mediated regulatory control of p21 is telomere length dependent.

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

2015 ◽  
Vol 32 (4) ◽  
pp. 229-238 ◽  
Author(s):  
Nicola S. Schutte ◽  
John M. Malouff
Keyword(s):  
Telomere Length ◽  
Meta Analysis ◽  
Leukocyte Telomere Length

scholarly journals Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis

2021 ◽  
Author(s):  
Richard J Allen ◽  
Amy Stockwell ◽  
Justin M Oldham ◽  
Beatriz Guillen-Guio ◽  
Carlos Flores ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Telomere Maintenance ◽  
Survival Times ◽  
Genome Wide ◽  
A Genome ◽  
Lung Condition ◽  
Independent Replication

AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic lung condition with poor survival times. We previously published a genome-wide meta-analysis of IPF risk across three studies with independent replication of associated variants in two additional studies. To maximise power and to generate more accurate effect size estimates, we performed a genome-wide meta-analysis across all five studies included in the previous IPF risk GWAS. We utilised the distribution of effect sizes across the five studies to assess the replicability of the results and identified five robust novel genetic association signals implicating mTOR signalling, telomere maintenance and spindle assembly genes in IPF risk.

scholarly journals Leukocyte telomere length and hippocampus volume: a meta-analysis

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1073 ◽  
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.

scholarly journals Revisiting Telomere Shortening in Cancer

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 107 ◽  
Author(s):  
Keiji Okamoto ◽  
Hiroyuki Seimiya
Keyword(s):  
Cancer Cells ◽  
Telomere Length ◽  
Prognostic Biomarker ◽  
Telomere Maintenance ◽  
Epigenetic Alterations ◽  
Telomere Shortening ◽  
Normal Tissues ◽  
Genome Wide ◽  
Unlimited Growth ◽  
Protective Structures

Telomeres, the protective structures of chromosome ends are gradually shortened by each cell division, eventually leading to senescence or apoptosis. Cancer cells maintain the telomere length for unlimited growth by telomerase reactivation or a recombination-based mechanism. Recent genome-wide analyses have unveiled genetic and epigenetic alterations of the telomere maintenance machinery in cancer. While telomerase inhibition reveals that longer telomeres are more advantageous for cell survival, cancer cells often have paradoxically shorter telomeres compared with those found in the normal tissues. In this review, we summarize the latest knowledge about telomere length alterations in cancer and revisit its rationality. Finally, we discuss the potential utility of telomere length as a prognostic biomarker.

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