title: Genetic determinants of leucocyte telomere length in children: a neglected and challenging field.
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.
authors: UMR INSERM U1122, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Université de Lorraine, Nancy, France.
authors: Maria G
authors: MG
authors: Stathopoulou
authors: Alexandros M
authors: AM
authors: Petrelis
authors: Jessica L
authors: JL
authors: Buxton
authors: Philippe
authors: P
authors: Froguel
authors: Alexandra I F
authors: AI
authors: Blakemore
authors: Sophie
authors: S
authors: Visvikis-Siest
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D000367:Age Factors; D015992:Body Mass Index; D002648:Child; D004781:Environmental Exposure; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008423:Maternal Age; D060888:Real-Time Polymerase Chain Reaction; D017678:Sex Distribution; D016615:Telomere / Q000235:genetics* / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D034501:Telomere-Binding Proteins
keywords: GWAS; childhood; leucocyte telomere length; polymorphisms