Genetic determinants of leucocyte telomere length in children: a neglected and challenging field.
Genetic determinants of leucocyte telomere length in children: a neglected and challenging field.
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儿童白细胞端粒长度的遗传决定因素：一个被忽视且具有挑战性的领域。
DOI：
10.1111/ppe.12173
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发表时间：
2015
影响因子：
2.8
通讯作者：
Stathopoulou MG
中科院分区：
文献类型：
--
作者：
Stathopoulou MG
研究背景端粒长度与人类多种疾病有关。全基因组关联研究（GWAS）已经确定了与白细胞端粒长度（LTL）相关的遗传变异。然而，这些研究仅限于成年人群。然而，儿童期是确定LTL的关键时期，对年龄特异性遗传决定因素的评估虽然被忽视，但可能非常重要。我们的目的是提供的见解和初步结果的遗传决定因素LTL在childhen.MethodsHealthy儿童（n= 322，年龄范围= 6.75-17岁）与可用的GWAS数据（Illumina人类CNV 370-Duo阵列）。使用多重定量真实的时间聚合酶链反应测量LTL。线性回归模型调整年龄，性别，父母的年龄在孩子的出生，和体重指数被用来测试的关联LTL与成人GWAS中确定的多态性，并执行一个发现-只有GWAS.ResultsThe先前GWAS-确定的变异在成人与LTL在我们的儿科样本。这种关联的缺乏不是由于与年龄或基因×基因相互作用的可能相互作用。此外，仅发现的GWAS方法证明了六种新的变异，达到了暗示性关联的水平（P≤ 5 × 10−5），并解释了儿童LTL的高百分比。需要在大规模儿童人群中进行研究以确认这些结果，可能通过儿童联盟可以更好地处理LTL遗传流行病学领域的方法学挑战。
BackgroundTelomere length is associated with a large range of human diseases. Genome‐wide association studies (GWAS) have identified genetic variants that are associated with leucocyte telomere length (LTL). However, these studies are limited to adult populations. Nevertheless, childhood is a crucial period for the determination of LTL, and the assessment of age‐specific genetic determinants, although neglected, could be of great importance. Our aim was to provide insights and preliminary results on genetic determinants of LTL in children.MethodsHealthy children (n= 322, age range = 6.75–17 years) with available GWAS data (Illumina Human CNV370‐Duo array) were included. The LTL was measured using multiplex quantitative real‐time polymerase chain reaction. Linear regression models adjusted for age, gender, parental age at child's birth, and body mass index were used to test the associations of LTL with polymorphisms identified in adult GWAS and to perform a discovery‐only GWAS.ResultsThe previously GWAS‐identified variants in adults were not associated with LTL in our paediatric sample. This lack of association was not due to possible interactions with age or gene × gene interactions. Furthermore, a discovery‐only GWAS approach demonstrated six novel variants that reached the level of suggestive association (P≤ 5 × 10−5) and explain a high percentage of children's LTL.ConclusionsThe study of genetic determinants of LTL in children may identify novel variants not previously identified in adults. Studies in large‐scale children populations are needed for the confirmation of these results, possibly through a childhood consortium that could better handle the methodological challenges of LTL genetic epidemiology field.
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DOI：
10.1016/j.mrfmmm.2011.04.003
发表时间：
2012-02-01
影响因子：
2.3
作者：
Aubert, Geraldine;Hills, Mark;Lansdorp, Peter M.
通讯作者：
Lansdorp, Peter M.
儿童端粒快速缩短。
影响因子：
20.3
作者：
Zeichner,SL;Palumbo,P;Feng,Y;Xiao,X;Gee,D;Sleasman,J;Goodenow,M;Biggar,R;Dimitrov,D
通讯作者：
Dimitrov,D
DOI：
10.1073/pnas.95.10.5607
发表时间：
1998-05-12
影响因子：
11.1
作者：
Frenck, RW;Blackburn, EH;Shannon, KM
通讯作者：
Shannon, KM
DOI：
10.1093/gerona/63.9.979
发表时间：
2008-09-01
影响因子：
5.1
作者：
Aviv, Abraham
通讯作者：
Aviv, Abraham