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Hum Genet. 2019 Jan;138(1):49-60. doi: 10.1007/s00439-018-1964-2. Epub 2018 Dec 10.

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

Author information

1
Department of Public Health Sciences, University of Chicago, Chicago, IL, 60615, USA.
2
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, 94158, USA.
3
Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
4
Division of Foodborne, Waterborne, and Environmental Diseases, Center for Disease Control, Atlanta, GA, 30333, USA.
5
Division of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, IL, 60637, USA.
6
UChicago Research Bangladesh, Dhaka, Bangladesh.
7
Research and Evaluation Division, BRAC, Dhaka, Bangladesh.
8
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
9
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
10
Department of Human Genetics, University of Chicago, Chicago, IL, 60615, USA.
11
Comprehensive Cancer Center, University of Chicago, Chicago, IL, 60615, USA.
12
Department of Medicine, University of Chicago, Chicago, IL, 60615, USA.
13
Department of Public Health Sciences, University of Chicago, Chicago, IL, 60615, USA. brandonpierce@uchicago.edu.
14
Department of Human Genetics, University of Chicago, Chicago, IL, 60615, USA. brandonpierce@uchicago.edu.
15
Comprehensive Cancer Center, University of Chicago, Chicago, IL, 60615, USA. brandonpierce@uchicago.edu.

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.

PMID:
30536049
PMCID:
PMC6616344
[Available on 2020-01-01]
DOI:
10.1007/s00439-018-1964-2
[Indexed for MEDLINE]

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