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

Philippe Froguel; Alexandra I. F. Blakemore; Sophie Visvikis-Siest; Maria G. Stathopoulou; Alexandros M. Petrelis; Jessica L. Buxton

doi:10.1111/ppe.12173

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

Philippe Froguel
, Alexandra I. F. Blakemore
, Sophie Visvikis-Siest
, Maria G. Stathopoulou
, Alexandros M. Petrelis
, Jessica L. Buxton

Research output: Contribution to journal › Article › peer-review

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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 Ôëñ 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.

Original language	English
Pages (from-to)	146-150
Journal	Paediatric and Perinatal Epidemiology
Volume	29
Issue number	2
Early online date	1 Feb 2015
DOIs	https://doi.org/10.1111/ppe.12173
Publication status	Published - 1 Mar 2015

Bibliographical note

Note: 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.

Keywords

Biological sciences

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10.1111/ppe.12173

Buxton-J-40220-AAMAccepted author manuscript, 1.12 MBLicence: Unspecified

http://dx.doi.org/10.1111/ppe.12173

Cite this

@article{e97441dd3f944431823290ec8b300153,

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 {\^O}{\"e}{\~n} 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.",

keywords = "Biological sciences",

author = "Philippe Froguel and Blakemore, \{Alexandra I. F.\} and Sophie Visvikis-Siest and Stathopoulou, \{Maria G.\} and Petrelis, \{Alexandros M.\} and Buxton, \{Jessica L.\}",

note = "Note: 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.",

year = "2015",

month = mar,

day = "1",

doi = "10.1111/ppe.12173",

language = "English",

volume = "29",

pages = "146--150",

journal = "Paediatric and Perinatal Epidemiology",

issn = "0269-5022",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "2",

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TY - JOUR

T1 - Genetic determinants of leucocyte telomere length in children

T2 - a neglected and challenging field

AU - Froguel, Philippe

AU - Blakemore, Alexandra I. F.

AU - Visvikis-Siest, Sophie

AU - Stathopoulou, Maria G.

AU - Petrelis, Alexandros M.

AU - Buxton, Jessica L.

N1 - Note: 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.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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 Ôëñ 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.

AB - 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 Ôëñ 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.

KW - Biological sciences

UR - https://www.ncbi.nlm.nih.gov/pubmed/25641522

U2 - 10.1111/ppe.12173

DO - 10.1111/ppe.12173

M3 - Article

C2 - 25641522

SN - 0269-5022

VL - 29

SP - 146

EP - 150

JO - Paediatric and Perinatal Epidemiology

JF - Paediatric and Perinatal Epidemiology

IS - 2

ER -

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

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