The heritability of leucocyte telomere length dynamics.
The heritability of leucocyte telomere length dynamics.
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DOI：
10.1136/jmedgenet-2014-102736
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发表时间：
2015-05
影响因子：
4
通讯作者：
Aviv A
中科院分区：
文献类型：
--
作者：
Hjelmborg JB;Dalgård C;Möller S;Steenstrup T;Kimura M;Christensen K;Kyvik KO;Aviv A
白细胞端粒长度(LTL)是一种与衰老和长寿有关的复杂性状。LTL动力学是由LTL及其年龄相关的磨损来定义的。有力但间接的证据表明，LTL在出生时及其在儿童时期的磨损在很大程度上解释了成人之间的LTL个体差异。许多研究已经估计了LTL的遗传度，但还没有一项研究评估与年龄相关的LTL损耗的遗传度。我们基于纵向评估(平均随访12 年)对355对同卵和297对同卵同卵双胞胎(基线年龄为19- 岁)进行了LTL动态遗传度检验。基线时低密度脂蛋白的遗传度估计为%(95%可信区间39%至83%)和22%(95%可信区间6%至49%)的共同环境影响。与年龄相关的LTL磨损率的遗传度估计为28%(95%可信区间为16%~44%)。单独独特的环境因素，估计为72%(95%可信区间56%至84%)影响LTL磨损率，没有共同环境影响的迹象。这是第一个估计LTL遗传力及其年龄相关损耗的研究。由于LTL在成人中的消耗要比儿童慢得多，而且LTL的长短在很大程度上是在成年前决定的，我们的发现表明，遗传性和早期生活环境是人类整个生命过程中LTL的主要决定因素。因此，深入了解在出生时影响LTL的因素及其在儿童时期的动态变化，对于理解端粒遗传学在人类衰老和长寿中的作用至关重要。
Leucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL variation among adults. A number of studies have estimated the heritability of LTL, but none has assessed the heritability of age-dependent LTL attrition. We examined the heritability of LTL dynamics based on a longitudinal evaluation (an average follow-up of 12 years) in 355 monozygotic and 297 dizygotic same-sex twins (aged 19–64 years at baseline). Heritability of LTL at baseline was estimated at 64% (95% CI 39% to 83%) with 22% (95% CI 6% to 49%) of shared environmental effects. Heritability of age-dependent LTL attrition rate was estimated at 28% (95% CI 16% to 44%). Individually unique environmental factors, estimated at 72% (95% CI 56% to 84%) affected LTL attrition rate with no indication of shared environmental effects. This is the first study that estimated heritability of LTL and also its age-dependent attrition. As LTL attrition is much slower in adults than in children and given that having a long or a short LTL is largely determined before adulthood, our findings suggest that heritability and early life environment are the main determinants of LTL throughout the human life course. Thus, insights into factors that influence LTL at birth and its dynamics during childhood are crucial for understanding the role of telomere genetics in human ageing and longevity.
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影响因子：
7.8
作者：
Benetos A;Kark JD;Susser E;Kimura M;Sinnreich R;Chen W;Steenstrup T;Christensen K;Herbig U;von Bornemann Hjelmborg J;Srinivasan SR;Berenson GS;Labat C;Aviv A
通讯作者：
Aviv A
影响因子：
4.5
作者：
Aubert G;Baerlocher GM;Vulto I;Poon SS;Lansdorp PM
通讯作者：
Lansdorp PM
影响因子：
7.8
作者：
Bakaysa, Stephanie L.;Mucci, Lorelei A.;Pedersen, Nancy L.
通讯作者：
Pedersen, Nancy L.
影响因子：
8.3
作者：
Jeanclos, E;Schork, NJ;Aviv, A
通讯作者：
Aviv, A
后代的白细胞端粒长度，父亲时代和精子中的端粒伸长率。
影响因子：
4.5
作者：
Kimura, Masayuki;Cherkas, Lynn F.;Kato, Bernet S.;Demissie, Serkalem;Hjelmborg, Jacob B.;Brimacombe, Michael;Cupples, Adrienne;Hunkin, Janice L.;Gardner, Jefferey P.;Lu, Xiaobin;Cao, Xiaojian;Sastrasinh, Malinee;Province, Michael A.;Hunt, Steven C.;Christensen, Kaare;Levy, Daniel;Spector, Tim D.;Aviv, Abraham
通讯作者：
Aviv, Abraham