Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

被引:351
作者
Broer, Linda [1 ,2 ]
Codd, Veryan [3 ]
Nyholt, Dale R. [4 ]
Deelen, Joris [2 ,5 ]
Mangino, Massimo [6 ]
Willemsen, Gonneke [7 ]
Albrecht, Eva [8 ]
Amin, Najaf [1 ]
Beekman, Marian [2 ,5 ]
de Geus, Eco J. C. [7 ]
Henders, Anjali [4 ]
Nelson, Christopher P. [3 ]
Steves, Claire J. [6 ]
Wright, Margie J. [4 ]
de Craen, Anton J. M. [9 ]
Isaacs, Aaron [1 ,10 ]
Matthews, Mary [3 ]
Moayyeri, Alireza [6 ]
Montgomery, Grant W. [4 ]
Oostra, Ben A. [1 ]
Vink, Jacqueline M. [7 ]
Spector, Tim D. [6 ]
Slagboom, P. Eline [2 ,5 ]
Martin, Nicholas G. [4 ]
Samani, Nilesh J. [3 ]
van Duijn, Cornelia M. [1 ,2 ]
Boomsma, Dorret I. [7 ]
机构
[1] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands
[2] Leiden Univ, Med Ctr, Netherlands Consortium Hlth Aging, Leiden, Netherlands
[3] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England
[4] Queensland Inst Med Res, Herston, Qld 4006, Australia
[5] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Leiden, Netherlands
[6] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
[7] Vrije Univ Amsterdam, Dept Biol Psychol, Netherlands Twin Register, Amsterdam, Netherlands
[8] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany
[9] Leiden Univ, Med Ctr, Deparment Gerontol & Geriatr, Leiden, Netherlands
[10] Ctr Med Syst Biol, Leiden, Netherlands
基金
澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 英国惠康基金;
关键词
telomere length; heritability; paternal age effect; NETHERLANDS TWIN REGISTER; GENETIC-VARIATION; COMMON VARIANTS; ASSOCIATION; MORTALITY; SURVIVAL; LOCUS; BLOOD; TERC; SEQUENCE;
D O I
10.1038/ejhg.2012.303
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x 10(-61)) than father-offspring correlation (r = 0.33; P-value = 7.01 x 10(-5)), and a significant positive association with paternal age at offspring birth (beta = 0.005; P-value = 7.01 x 10(-5)). Interestingly, a significant and quite substantial correlation in TL between spouses (r = 0.25; P-value = 2.82 x 10(-30)) was seen, which appeared stronger in older spouse pairs (mean age >= 55 years; r = 0.31; P-value = 4.27 x 10(-23)) than in younger pairs (mean age <55 years; r = 0.20; P-value = 3.24 x 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.
引用
收藏
页码:1163 / 1168
页数:6
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