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Telomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors. Our results confirm that TL is a largely heritable trait, primarily with mother's, and, to a lesser extent, with father's TL having the strongest influence on the offspring. In this cohort, mother's, but not father's age at conception was positively linked to offspring TL. Age-related TL attrition of 40 bp/year had relatively small influence on TL variability. Finally, we have identified TL-associated variations in ribonuclease reductase catalytic subunit M1 (RRM1 gene), which is known to regulate telomere maintenance in yeast. We also highlight the importance of multivariate approach and the limitations of existing tools for the analysis of TL as a polygenic heritable quantitative trait.

Original publication

DOI

10.1038/s41598-019-55109-7

Type

Journal article

Journal

Scientific reports

Publication Date

12/2019

Volume

9

Addresses

Bioinformatics Group, Institute of Molecular Biology NAS RA, 7 Hasratyan str., 0014, Yerevan, Armenia. l_nersisyan@mb.sci.am.

Keywords

Genome of the Netherlands consortium, Telomere, Humans, Ribonucleoside Diphosphate Reductase, Linear Models, Age Factors, Maternal Age, Sex Factors, Paternal Age, Polymorphism, Single Nucleotide, Models, Genetic, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Netherlands, Female, Male, Genome-Wide Association Study, Young Adult, Telomere Homeostasis, Datasets as Topic, Maternal Inheritance, Whole Genome Sequencing