WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene

Lilit Nersisyan*, Maria Nikoghosyan, Arsen Arakelyan, Genome of the Netherlands Consortium, Aaron Isaacs

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

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 languageEnglish
Article number18758
Pages (from-to)18758
Number of pages9
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 10 Dec 2019
Externally publishedYes

Keywords

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Child
  • Datasets as Topic
  • Female
  • Genome-Wide Association Study
  • Humans
  • Linear Models
  • Male
  • Maternal Age
  • Maternal Inheritance
  • Middle Aged
  • Models, Genetic
  • Netherlands
  • Paternal Age
  • Polymorphism, Single Nucleotide
  • Ribonucleoside Diphosphate Reductase/genetics
  • Sex Factors
  • Telomere Homeostasis/genetics
  • Telomere/metabolism
  • Whole Genome Sequencing
  • Young Adult
  • METAANALYSIS
  • HUMANS
  • PATERNAL AGE
  • SUBUNIT
  • CELLS
  • SIZE
  • LUNG-CANCER
  • PROTEINS
  • ASSOCIATION

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