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对 19713 名研究对象的端粒长度进行的荟萃分析显示,端粒长度具有高度遗传性,存在较强的母系遗传和父系年龄效应。

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

机构信息

1] Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Aging, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Eur J Hum Genet. 2013 Oct;21(10):1163-8. doi: 10.1038/ejhg.2012.303. Epub 2013 Jan 16.

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.

摘要

端粒长度 (TL) 与衰老和死亡率有关,但个体差异也受到遗传因素的影响,先前的研究报告遗传率估计值在 34%至 82%之间。在这里,我们在六个大型独立队列研究中调查了 TL 的遗传率、遗传模式和父母出生时年龄对 TL 的影响,共有 19713 名参与者。TL 遗传率的荟萃分析估计值为 0.70(95%置信区间 0.64-0.76),基于双胞胎和其他家庭成员的结果模式非常相似。我们观察到母亲与子女之间的相关性更强(r=0.42;P 值=3.60×10(-61)),而父亲与子女之间的相关性较弱(r=0.33;P 值=7.01×10(-5)),并且与父亲在子女出生时的年龄呈显著正相关(β=0.005;P 值=7.01×10(-5))。有趣的是,我们在配偶之间观察到 TL 之间存在显著且相当大的相关性(r=0.25;P 值=2.82×10(-30)),在年龄较大的配偶(平均年龄≥55 岁;r=0.31;P 值=4.27×10(-23))中比在年龄较小的配偶(平均年龄<55 岁;r=0.20;P 值=3.24×10(-10))中更强。总之,我们发现 TL 具有很高且非常一致的遗传率估计值,存在母体遗传成分的证据,并且与父亲的年龄呈正相关。

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