@article{adf03bb4046c4ad78a219e83fc6f4440,
title = "Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect",
abstract = "Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64-0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother-offspring (r=0.42; P-value=3.60 × 10 -61) than father-offspring correlation (r=0.33; P-value=7.01 × 10 -5), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10 -5). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10 -30) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10 -23) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10 -10). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.",
keywords = "heritability, paternal age effect, telomere length",
author = "Linda Broer and Veryan Codd and Nyholt, {Dale R.} and Joris Deelen and Massimo Mangino and Gonneke Willemsen and Eva Albrecht and Najaf Amin and Marian Beekman and {De Geus}, {Eco J.C.} and Anjali Henders and Nelson, {Christopher P.} and Steves, {Claire J.} and Wright, {Margie J.} and {De Craen}, {Anton J.M.} and Aaron Isaacs and Mary Matthews and Alireza Moayyeri and Montgomery, {Grant W.} and Oostra, {Ben A.} and Vink, {Jacqueline M.} and Spector, {Tim D.} and Slagboom, {P. Eline} and Martin, {Nicholas G.} and Samani, {Nilesh J.} and {Van Duijn}, {Cornelia M.} and Boomsma, {Dorret I.}",
note = "Funding Information: Telomere length assessment was co-funded by the European Community{\textquoteright}s Seventh Framework Programme (FP7/2007-2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413 and NHMRC-European Union Collaborative Research Grant 496739. GWM and DRN were supported by the NHMRC Fellowship (619667) and ARC Future Fellowship (FT0991022) schemes, respectively. TwinsUK: The study was funded by the Wellcome Trust; European Community{\textquoteright}s Seventh Framework Programme (FP7/2007-2013), ENGAGE project grant agreement (HEALTH-F4-2007-201413). The study also receives support from the Dept of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London. TDS is an NIHR senior Investigator and is holder of an ERC Advanced Principal Investigator award. Genotyping was performed by The Wellcome Trust Sanger Institute, support of the National Eye Institute via an NIH/CIDR genotyping project. Funding Information: ERF: The study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC and the Centre for Medical Systems Biology (CMSB). Telomere length assessment was supported through funds from the European Community{\textquoteright}s Seventh Framework Programme (FP7/ 2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4-2007-201413. We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and Peter Snijders for his help in data collection. GRAPHIC: The GRAPHIC study was funded by the BHF. VC and NJS are supported by the BHF and VC, CN and NJS are supported by the Leicester National Institute of Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease. Additionally, this research was supported through funds from The European Community{\textquoteright}s Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4-2007-201413. LLS: We thank all participants of the Leiden Longevity Study. The research leading to these results has received funding from the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007-2011) under grant agreement number 259679. This study was supported by a grant from the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology and the Netherlands Consortium for Healthy Ageing (grant 050-060-810), all in the framework of the Netherlands Genomics Initiative, Netherlands Organization for Scientific Research (NWO), and by Unilever Colworth. NTR: We thank all participants in the Netherlands Twin Register. Research was funded by the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW grants 904-61-090, 985-10-002,904-61-193,480-04-004, 400-05-717, Addiction-31160008 Middelgroot-911-09-032, Spinozapremie 56-464-14192), Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007), the VU University{\textquoteright}s Institute for Health and Care Research (EMGO + ), the European Community{\textquoteright}s Seventh Framework Program (FP7/ 2007-2013), ENGAGE (HEALTH-F4-2007-201413) and the European Science Council (ERC–230374 and ERC-284167). QIMR: We thank Marlene Grace and Ann Eldridge for twin recruitment and data collection, Lisa Bardsley for preparation of DNA samples, David Smyth for IT/database support and the twins and their families for their participation. Data collection was supported by grants to NGM and MJW from the Australian Research Council and Australian National Health and Medical Research Council (NHMRC).",
year = "2013",
month = oct,
doi = "10.1038/ejhg.2012.303",
language = "English",
volume = "21",
pages = "1163--1168",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Springer Nature",
number = "10",
}