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

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 larg... Mehr ...

Verfasser: Nersisyan, Lilit
Nikoghosyan, Maria
Francioli, Laurent C.
Menelaou, Androniki
Pulit, Sara L.
Elbers, Clara C.
Kloosterman, Wigard P.
van Setten, Jessica
Nijman, Isaäc J.
Renkens, Ivo
de Bakker, Paul I. W.
van Dijk, Freerk
Neerincx, Pieter B. T.
Deelen, Patrick
Kanterakis, Alexandros
Dijkstra, Martijn
Byelas, Heorhiy
van der Velde, K. Joeri
Platteel, Mathieu
Swertz, Morris A.
Wijmenga, Cisca
Palamara, Pier Francesco
Pe’er, Itsik
Ye, Kai
Lameijer, Eric-Wubbo
Moed, Matthijs H.
Beekman, Marian
de Craen, Anton J. M.
Suchiman, H. Eka D.
Slagboom, P. Eline
Guryev, Victor
Abdellaoui, Abdel
Jan Hottenga, Jouke
Kattenberg, Mathijs
Willemsen, Gonneke
Boomsma, Dorret I.
van Leeuwen, Elisabeth M.
Karssen, Lennart C.
Amin, Najaf
Rivadeneira, Fernando
Isaacs, Aaron
Hofman, Albert
Uitterlinden, André G.
van Duijn, Cornelia M.
van Oven, Mannis
Kayser, Manfred
Vermaat, Martijn
Laros, Jeroen F. J.
den Dunnen, Johan T.
Dokumenttyp: Artikel
Erscheinungsdatum: 2019
Reihe/Periodikum: Scientific Reports ; volume 9, issue 1 ; ISSN 2045-2322
Verlag/Hrsg.: Springer Science and Business Media LLC
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29044313
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://dx.doi.org/10.1038/s41598-019-55109-7

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.