1. WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene
- Author
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Nersisyan, Lilit, Nikoghosyan, Maria, Arakelyan, Arsen, Francioli, Laurent, Menelaou, A. (Androniki), Pulit, S.L. (Sara L.), Elbers, C.C. (Clara C.), Kloosterman, Wigard, van Setten, J. (Jessica), Nijman, Isaac, Renkens, Ivo, de Bakker, P.I.W. (Paul I. W.), Dijk, Freerk, Neerincx, Pieter, Deelen, Patrick, Kanterakis, Alexandros, Dijkstra, Martijn, Byelas, H. (Heorhiy), van der Velde, K.J. (K. Joeri), Platteel, Mathieu, Swertz, M.A. (Morris A.), Wijmenga, Cisca, Palamara, P.F. (Pier Francesco), Pe’er, I. (Itsik), Ye, K. (Kai), Lameijer, Eric-Wubbo, Moed, M.H. (Matthijs H.), Beekman, M. (Marian), Craen, Anton, Suchiman, H.E.D. (H. Eka D.), Slagboom, Eline, Guryev, Victor, Abdellaoui, Abdel, Jan Hottenga, J. (Jouke), Kattenberg, M. (Mathijs), Willemsen, Gonneke, Boomsma, Dorret, van Leeuwen, E.M. (Elisabeth M.), Karssen, Lennart, Amin, N. (Najaf), Rivadeneira, F. (Fernando), Isaacs, A. (Aaron), Hofman, A. (Albert), Uitterlinden, André, Duijn, Cornelia, van Oven, M. (Mannis), Kayser, M. (Manfred), Vermaat, Martijn, Laros, Jeroen, Dunnen, Johan, Enckevort, David, Mei, Hailiang, Li, M. (Mingkun), Stoneking, M. (Mark), Schaik, Barbera, Bot, Jan, Marschall, Tobias, Schönhuth, Alexander, Hehir-Kwa, Jayne, Handsaker, Robert, Polak, P. (Paz), Sohail, M. (Mashaal), Vuzman, D. (Dana), Estrada, Karol, McCarroll, S.A. (Steven A.), Sunyaev, S.R. (Shamil R.), Hormozdiari, Fereydoun, Koval, Vyacheslav, Medina-Gomez, C. (Carolina), Oostra, B. (Ben), Veldink, Jan, van den Berg, L.H. (Leonard H.), Pitts, S.J. (Steven J.), Potluri, S. (Shobha), Sundar, P. (Purnima), Cox, D.R. (David R.), Knijff, Peter, Li, Q. (Qibin), Li, Y. (Yingrui), Du, Yuanping, Chen, Ruoyan, Cao, H. (Hongzhi), Wang, J. (Jun), Li, N. (Ning), Cao, S. (Sujie), Bovenberg, Jasper, Ommen, Gert-Jan, The Genome of the Netherlands Consortium, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Department of Health and Life Sciences, Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Experimental Immunology, CCA - Cancer biology and immunology, Epidemiology and Data Science, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology, Internal Medicine, Genetic Identification, Clinical Genetics, and Genome of the Netherlands Consortium
- Subjects
Male ,Telomere Homeostasis/genetics ,Netherlands Twin Register (NTR) ,Non-Mendelian inheritance ,lcsh:Medicine ,Datasets as Topic ,Ribonucleoside Diphosphate Reductase/genetics ,Genome of the Netherlands consortium ,Genome informatics ,Genome ,0302 clinical medicine ,Models ,80 and over ,Inheritance Patterns ,lcsh:Science ,Child ,Netherlands ,Genetics ,Aged, 80 and over ,0303 health sciences ,Multidisciplinary ,Age Factors ,Functional genomics ,Single Nucleotide ,ASSOCIATION ,Telomere ,Middle Aged ,030220 oncology & carcinogenesis ,Trait ,Female ,Maternal Inheritance ,Biotechnology ,Maternal Age ,Adult ,Ribonucleoside Diphosphate Reductase ,Adolescent ,Offspring ,PROTEINS ,Quantitative trait locus ,Biology ,Polymorphism, Single Nucleotide ,Article ,Paternal Age ,03 medical and health sciences ,Young Adult ,Sex Factors ,LUNG-CANCER ,Genetic ,Humans ,Polymorphism ,Telomere/metabolism ,General ,Gene ,METAANALYSIS ,030304 developmental biology ,Aged ,Whole genome sequencing ,Models, Genetic ,Whole Genome Sequencing ,Human Genome ,lcsh:R ,Telomere Homeostasis ,SIZE ,SUBUNIT ,CELLS ,Linear Models ,lcsh:Q ,Genome-Wide Association Study - 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.
- Published
- 2019
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