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Genetic Determinants of Leucocyte Telomere Length in Children: a Neglected and Challenging Field
Author(s) -
Stathopoulou Maria G.,
Petrelis Alexandros M.,
Buxton Jessica L.,
Froguel Philippe,
Blakemore Alexandra I. F.,
VisvikisSiest Sophie
Publication year - 2015
Publication title -
paediatric and perinatal epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.667
H-Index - 88
eISSN - 1365-3016
pISSN - 0269-5022
DOI - 10.1111/ppe.12173
Subject(s) - genome wide association study , medicine , telomere , genetic association , genetics , gene , single nucleotide polymorphism , biology , genotype
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 ( I llumina H uman CNV 370‐ D uo 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.