Abstract
Background
Leukocyte telomere length (LTL), an indicator of aging, is influenced by both genetic and environmental factors; however, its heritability is unknown. We determined heritability and inheritance patterns of telomere length across three generations of families.
Methods
We analyzed 287 individuals from three generations of 41 Korean families, including newborns, parents, and grandparents. LTL (the ratio of telomere repeat copy number to single gene copy number) was measured by quantitative real-time PCR. We estimated heritability using the SOLAR software maximum-likelihood variance component methods and a pedigree dataset. With adjustment for age and length of marriage, Pearson’s partial correlation was performed for spousal pairs.
Results
Heritability of LTL was high in all participants (h2 = 0.64). There were no significant differences in correlation coefficients of telomere length between paternal and maternal lines. There was a positive LTL correlation in grandfather–grandmother pairs (r = 0.25, p = 0.03) but not in father–mother pairs. After adjusting for age and length of marriage, the relationship between telomere lengths in grandfathers and grandmothers disappeared. There were inverse correlations between spousal rank differences of telomere length and length of marriage.
Conclusions
LTL is highly heritable without a sex-specific inheritance pattern and may be influenced by a shared environment.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Eisenberg, D. T. An evolutionary review of human telomere biology: the thrifty telomere hypothesis and notes on potential adaptive paternal effects. Am. J. Hum. Biol. 23, 149–167 (2011).
Armanios, M. Telomeres and age-related disease: how telomere biology informs clinical paradigms. J. Clin. Invest. 123, 996–1002 (2013).
Huda, N., Tanaka, H., Herbert, B. S., Reed, T. & Gilley, D. Shared environmental factors associated with telomere length maintenance in elderly male twins. Aging Cell 6, 709–713 (2007).
Bischoff, C. et al. The heritability of telomere length among the elderly and oldest-old. Twin Res. Hum. Genet. 8, 433–439 (2005).
Broer, L. et al. Meta-analysis of telomere length in 19,713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect. Eur. J. Hum. Genet. 21, 1163–1168 (2013).
Hjelmborg, J. B. et al. The heritability of leucocyte telomere length dynamics. J. Med. Genet. 52, 297–302 (2015).
Honig, L. S. et al. Heritability of telomere length in a study of long-lived families. Neurobiol. Aging 36, 2785–2790 (2015).
Jeanclos, E. et al. Telomere length inversely correlates with pulse pressure and is highly familial. Hypertension 36, 195–200 (2000).
Benetos, A. et al. Tracking and fixed ranking of leukocyte telomere length across the adult life course. Aging Cell 12, 615–621 (2013).
Nawrot, T. S., Staessen, J. A., Gardner, J. P. & Aviv, A. Telomere length and possible link to X chromosome. Lancet 363, 507–510 (2004).
Nordfjall, K., Svenson, U., Norrback, K. F., Adolfsson, R. & Roos, G. Large-scale parent-child comparison confirms a strong paternal influence on telomere length. Eur. J. Hum. Genet. 18, 385–389 (2010).
Nordfjall, K., Larefalk, A., Lindgren, P., Holmberg, D. & Roos, G. Telomere length and heredity: Indications of paternal inheritance. Proc. Natl Acad. Sci. USA 102, 16374–16378 (2005).
Njajou, O. T. et al. Telomere length is paternally inherited and is associated with parental lifespan. Proc. Natl Acad. Sci. USA 104, 12135–12139 (2007).
Factor-Litvak, P. et al. Leukocyte telomere length in newborns: implications for the role of telomeres in human disease. Pediatrics 137, e20153927 (2016).
Eisenberg, D. T. Inconsistent inheritance of telomere length (TL): is offspring TL more strongly correlated with maternal or paternal TL? Eur. J. Hum. Genet. 22, 8–9 (2014).
Al-Attas, O. S. et al. Circulating leukocyte telomere length is highly heritable among families of Arab descent. BMC Med. Genet. 13, 38 (2012).
Eisenberg, D. T., Hayes, M. G. & Kuzawa, C. W. Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants. Proc. Natl Acad. Sci. USA 109, 10251–10256 (2012).
Han, C. W., Lee, E. J., Iwaya, T., Kataoka, H. & Kohzuki, M. Development of the Korean version of short-form 36-item health survey: Health related QOL of healthy elderly people and elderly patients in Korea. Tohoku J. Exp. Med. 203, 189–194 (2004).
Roberts, H. C. et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing 40, 423–429 (2011).
Cawthon, R. M. Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res. 37, e21 (2009).
Almasy, L. & Blangero, J. Multipoint quantitative-trait linkage analysis in general pedigrees. Am. J. Hum. Genet. 62, 1198–1211 (1998).
Koran, M. E. et al. Impact of family structure and common environment on heritability estimation for neuroimaging genetics studies using Sequential Oligogenic Linkage Analysis Routines. J. Med. Imaging (Bellingham) 1, 014005 (2014).
Diedenhofen, B. & Musch, J. cocor: a comprehensive solution for the statistical comparison of correlations. PLoS ONE 10, e012194 (2015).
De Meyer, T. et al. A non-genetic, epigenetic-like mechanism of telomere length inheritance? Eur. J. Hum. Genet. 22, 10–11 (2014).
De Meyer, T. & Eisenberg, D. T. A. Possible technical and biological explanations for the ‘parental telomere length inheritance discrepancy' enigma. Eur. J. Hum. Genet. 23, 3–4 (2015).
Brown, L., Needham, B. & Ailshire, J. Telomere length among older U.S. adults: differences by race/ethnicity, gender, and age. J. Aging Health 29, 1350–1366 (2017).
Akkad, A. et al. Telomere length in small-for-gestational-age babies. BJOG 113, 318–323 (2006).
Herlin, M. et al. Exploring telomere length in mother-newborn pairs in relation to exposure to multiple toxic metals and potential modifying effects by nutritional factors. BMC Med. 17, 77 (2019).
Neuner, B. et al. Telomere length is not related to established cardiovascular risk factors but does correlate with red and white blood cell counts in a German blood donor population. PLoS ONE 10, e0139308 (2015).
Bijnens, E. et al. Lower placental telomere length may be attributed to maternal residential traffic exposure; a twin study. Environ. Int. 79, 1–7 (2015).
Wojcicki, J. M. et al. Cord blood telomere length in Latino infants: relation with maternal education and infant sex. J. Perinatol. 36, 235–241 (2016).
Acknowledgements
This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, Information and Communications Technology (ICT) & Future Planning (No. 2012R1A1A2041924 to J.-H.K.).
Author information
Authors and Affiliations
Contributions
This manuscript is based on the first author’s doctoral dissertation from the Graduate School of Yonsei University. J.-H. Kim was a major contributor toward acquiring the data and writing the manuscript. C.M.N. contributed to statistical analyses and revised the manuscript critically for important intellectual content. D.-C.L., J.-H. Ko, H.B., and I.L. contributed to laboratory analyses and revised the manuscript critically for important intellectual content. G.J.K. was involved with data collection and revised the manuscript critically for important intellectual content. B.W.K. revised the manuscript critically for important intellectual content. D.-C.L. was responsible for the study conception and design, as well as for intellectual content of the paper. All authors read and approved the final version of manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Kim, JH., Nam, C.M., Lee, D. et al. Heritability of telomere length across three generations of Korean families. Pediatr Res 87, 1060–1065 (2020). https://doi.org/10.1038/s41390-019-0699-7
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41390-019-0699-7
This article is cited by
-
A comparison of feature selection methodologies and learning algorithms in the development of a DNA methylation-based telomere length estimator
BMC Bioinformatics (2023)
-
Genetically determined telomere length and multiple myeloma risk and outcome
Blood Cancer Journal (2021)
-
Shortening of the leucocytes’ telomeres length in T2DM independent of age and telomerase activity
Acta Diabetologica (2020)
