Genetic determinants of leucocyte telomere length in children : a neglected and challenging field

Stathopoulou, Maria G., Petrelis, Alexandros M., Buxton, Jessica L., Froguel, Philippe, Blakemore, Alexandra I. F. and Visvikis-Siest, Sophie (2015) Genetic determinants of leucocyte telomere length in children : a neglected and challenging field. Paediatric and Perinatal Epidemiology, 29(2), pp. 146-150. ISSN (print) 0269-5022

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Abstract

BACKGROUND: Telomere 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. METHODS: Healthy 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. RESULTS: The 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. CONCLUSIONS: The 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.

Item Type: Article
Additional Information: The study was funded by the "BioIntelligence" project. The Section of Investigative Medicine at Imperial College London is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. The work of JB and AIFB was also funded by The Wellcome Trust, MRC and Diabetes UK.
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017) > School of Life Sciences
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Depositing User: Jessica Buxton
Date Deposited: 11 Dec 2017 09:02
Last Modified: 11 Dec 2017 14:17
DOI: https://doi.org/10.1111/ppe.12173
URI: http://eprints.kingston.ac.uk/id/eprint/40220

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