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Human Genetics

, Volume 138, Issue 1, pp 49–60 | Cite as

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

  • Dayana A. Delgado
  • Chenan Zhang
  • Kevin Gleason
  • Kathryn Demanelis
  • Lin S. Chen
  • Jianjun Gao
  • Shantanu Roy
  • Justin Shinkle
  • Mekala Sabarinathan
  • Maria Argos
  • Lin Tong
  • Alauddin Ahmed
  • Tariqul Islam
  • Muhammad Rakibuz-Zaman
  • Golam Sarwar
  • Hasan Shahriar
  • Mahfuzar Rahman
  • Muhammad Yunus
  • Jennifer A. Doherty
  • Farzana Jasmine
  • Muhammad G. Kibriya
  • Habibul Ahsan
  • Brandon L. PierceEmail author
Original Investigation

Abstract

Leukocyte 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 h2 have 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 5069 Bangladeshi adults with substantial relatedness. For each of the 6318 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 Tshared and 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 Tshared and (ΔLTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs (ϕ > 0.05), the association between Tshared and (ΔLTL)2 (P = 0.01) was stronger than the association between ϕ and (ΔLTL)2 (P = 0.43). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere “reprogramming” during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direct transmission of telomeres.

Notes

Acknowledgements

This work was supported by the National Institutes of Health (R01 ES020506, U01 HG007601, P42 ES10349, R01 CA107431, R01 CA102484, P30 CA014599). The authors thank all the men and women who participated in HEALS and BEST and all research staff who contributed to data collection. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

439_2018_1964_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1140 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Dayana A. Delgado
    • 1
  • Chenan Zhang
    • 1
    • 2
  • Kevin Gleason
    • 1
  • Kathryn Demanelis
    • 1
  • Lin S. Chen
    • 1
  • Jianjun Gao
    • 3
  • Shantanu Roy
    • 1
    • 4
  • Justin Shinkle
    • 1
  • Mekala Sabarinathan
    • 1
  • Maria Argos
    • 5
  • Lin Tong
    • 1
  • Alauddin Ahmed
    • 6
  • Tariqul Islam
    • 6
  • Muhammad Rakibuz-Zaman
    • 6
  • Golam Sarwar
    • 6
  • Hasan Shahriar
    • 6
  • Mahfuzar Rahman
    • 7
  • Muhammad Yunus
    • 8
  • Jennifer A. Doherty
    • 9
  • Farzana Jasmine
    • 1
  • Muhammad G. Kibriya
    • 1
  • Habibul Ahsan
    • 1
    • 10
    • 11
    • 12
  • Brandon L. Pierce
    • 1
    • 10
    • 11
    Email author
  1. 1.Department of Public Health SciencesUniversity of ChicagoChicagoUSA
  2. 2.Department of Epidemiology and BiostatisticsUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Department of PsychiatryUniversity of California San DiegoLa JollaUSA
  4. 4.Division of Foodborne, Waterborne, and Environmental DiseasesCenter for Disease ControlAtlantaUSA
  5. 5.Division of Epidemiology and BiostatisticsUniversity of Illinois at ChicagoChicagoUSA
  6. 6.UChicago Research BangladeshDhakaBangladesh
  7. 7.Research and Evaluation DivisionBRACDhakaBangladesh
  8. 8.International Centre for Diarrhoeal Disease ResearchDhakaBangladesh
  9. 9.Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  10. 10.Department of Human GeneticsUniversity of ChicagoChicagoUSA
  11. 11.Comprehensive Cancer CenterUniversity of ChicagoChicagoUSA
  12. 12.Department of MedicineUniversity of ChicagoChicagoUSA

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