TY - JOUR
T1 - WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene
AU - Genome Netherlands Consortium
AU - Nersisyan, Lilit
AU - Nikoghosyan, Maria
AU - Francioli, Laurent C.
AU - Menelaou, Androniki
AU - Pulit, Sara L.
AU - Elbers, Clara C.
AU - Kloosterman, Wigard P.
AU - van Setten, Jessica
AU - Nijman, Isaac J.
AU - Renkens, Ivo
AU - de Bakker, Paul I. W.
AU - van Dijk, Freerk
AU - Neerincx, Pieter B. T.
AU - Deelen, Patrick
AU - Kanterakis, Alexandros
AU - Dijkstra, Martijn
AU - Byelas, Heorhiy
AU - van der Velde, K. Joeri
AU - Platteel, Mathieu
AU - Swertz, Morris A.
AU - Wijmenga, Cisca
AU - Palamara, Pier Francesco
AU - Pe'er, Itsik
AU - Ye, Kai
AU - Lameijer, Eric-Wubbo
AU - Moed, Matthijs H.
AU - Beekman, Marian
AU - de Craen, Anton J. M.
AU - Suchiman, H. Eka D.
AU - Slagboom, P. Eline
AU - Guryev, Victor
AU - Abdellaoui, Abdel
AU - Hottenga, Jouke Jan
AU - Kattenberg, Mathijs
AU - Willemsen, Gonneke
AU - Boomsma, Dorret I.
AU - van Leeuwen, Elisabeth M.
AU - Karssen, Lennart C.
AU - Amin, Najaf
AU - Rivadeneira, Fernando
AU - Isaacs, Aaron
AU - Hofman, Albert
AU - Uitterlinden, Andre G.
AU - van Duijn, Cornelia M.
AU - van Oven, Mannis
AU - Kayser, Manfred
AU - Vermaat, Martijn
AU - Laros, Jeroen F. J.
AU - van Enckevort, David
AU - Veldink, Jan H.
PY - 2019/12/10
Y1 - 2019/12/10
N2 - 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.
AB - 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.
KW - PATERNAL AGE
KW - LUNG-CANCER
KW - ASSOCIATION
KW - METAANALYSIS
KW - PROTEINS
KW - SUBUNIT
KW - HUMANS
KW - CELLS
KW - SIZE
U2 - 10.1038/s41598-019-55109-7
DO - 10.1038/s41598-019-55109-7
M3 - Article
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 18758
ER -