Childhood DNA methylation as a marker of early life rapid weight gain and subsequent overweight
Childhood DNA methylation as a marker of early life rapid weight gain and subsequent overweight
Background: High early postnatal weight gain has been associated with childhood adiposity; however, the mechanism remains unknown. DNA methylation is a hypothesised mechanism linking early life exposures and subsequent disease. However, epigenetic changes associated with high early weight gain have not previously been investigated. Our aim was to investigate the associations between early weight gain, peripheral blood DNA methylation, and subsequent overweight/obese. Data from the UK Avon Longitudinal study of Parents and Children (ALSPAC) cohort were used to estimate associations between early postnatal weight gain and epigenome-wide DNA CpG site methylation (Illumina 450 K Methylation Beadchip) in blood in childhood (n = 125) and late adolescence (n = 96). High weight gain in the first year (a change in weight z‐scores > 0.67), both unconditional (rapid weight gain) and conditional on birthweight (rapid thrive), was related to individual CpG site methylation and across regions using the meffil pipeline, with and without adjustment for cell type proportions, and with 5% false discovery rate correction. Variation in methylation at high weight gain-associated CpG sites was then examined with regard to body composition measures in childhood and adolescence. Replication of the differentially methylated CpG sites was sought using whole-blood DNA samples from 104 children from the UK Southampton Women’s Survey. Results: Rapid infant weight gain was associated with small (+ 1% change) increases in childhood methylation (age 7) for two distinct CpG sites (cg01379158 (NT5M) and cg11531579 (CHFR)). Childhood methylation at one of these CpGs (cg11531579) was also higher in those who experienced rapid weight gain and were subsequently overweight/obese in adolescence (age 17). Rapid weight gain was not associated with differential DNA methylation in adolescence. Childhood methylation at the cg11531579 site was also suggestively associated with rapid weight gain in the replication cohort. Conclusions: This study identified associations between rapid weight gain in infancy and small increases in childhood methylation at two CpG sites, one of which was replicated and was also associated with subsequent overweight/obese. It will be important to determine whether loci are markers of early rapid weight gain across different, larger populations. The mechanistic relevance of these differentially methylated sites requires further investigation
ALSPAC, Conditional weight gain, DNA methylation, DOHAD, EWAS, Epigenetics, Rapid weight gain, SWS
Robinson, N.
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Brown, H.
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Antoun, Elie
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Godfrey, Keith
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Hanson, Mark
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Lillycrop, Karen
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Crozier, Sarah
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Murray, Robert
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Pearce, M.S.
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Relton, C.L.
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Albani, V.
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McKay, J.A.
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19 January 2021
Robinson, N.
2153253d-f40c-46ba-a96a-8dc1aa952d4c
Brown, H.
127d80f2-c65b-4622-9bb0-31861ec75b4d
Antoun, Elie
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Godfrey, Keith
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Hanson, Mark
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Lillycrop, Karen
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Crozier, Sarah
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Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Pearce, M.S.
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Relton, C.L.
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Albani, V.
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McKay, J.A.
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Robinson, N., Brown, H., Antoun, Elie, Godfrey, Keith, Hanson, Mark, Lillycrop, Karen, Crozier, Sarah, Murray, Robert, Pearce, M.S., Relton, C.L., Albani, V. and McKay, J.A.
(2021)
Childhood DNA methylation as a marker of early life rapid weight gain and subsequent overweight.
Clinical Epigenetics, 13 (1), [8].
(doi:10.1186/s13148-020-00952-z).
Abstract
Background: High early postnatal weight gain has been associated with childhood adiposity; however, the mechanism remains unknown. DNA methylation is a hypothesised mechanism linking early life exposures and subsequent disease. However, epigenetic changes associated with high early weight gain have not previously been investigated. Our aim was to investigate the associations between early weight gain, peripheral blood DNA methylation, and subsequent overweight/obese. Data from the UK Avon Longitudinal study of Parents and Children (ALSPAC) cohort were used to estimate associations between early postnatal weight gain and epigenome-wide DNA CpG site methylation (Illumina 450 K Methylation Beadchip) in blood in childhood (n = 125) and late adolescence (n = 96). High weight gain in the first year (a change in weight z‐scores > 0.67), both unconditional (rapid weight gain) and conditional on birthweight (rapid thrive), was related to individual CpG site methylation and across regions using the meffil pipeline, with and without adjustment for cell type proportions, and with 5% false discovery rate correction. Variation in methylation at high weight gain-associated CpG sites was then examined with regard to body composition measures in childhood and adolescence. Replication of the differentially methylated CpG sites was sought using whole-blood DNA samples from 104 children from the UK Southampton Women’s Survey. Results: Rapid infant weight gain was associated with small (+ 1% change) increases in childhood methylation (age 7) for two distinct CpG sites (cg01379158 (NT5M) and cg11531579 (CHFR)). Childhood methylation at one of these CpGs (cg11531579) was also higher in those who experienced rapid weight gain and were subsequently overweight/obese in adolescence (age 17). Rapid weight gain was not associated with differential DNA methylation in adolescence. Childhood methylation at the cg11531579 site was also suggestively associated with rapid weight gain in the replication cohort. Conclusions: This study identified associations between rapid weight gain in infancy and small increases in childhood methylation at two CpG sites, one of which was replicated and was also associated with subsequent overweight/obese. It will be important to determine whether loci are markers of early rapid weight gain across different, larger populations. The mechanistic relevance of these differentially methylated sites requires further investigation
Text
ALSPAC paper -accepted pre-formatted 21-10-20
- Accepted Manuscript
More information
Accepted/In Press date: 16 October 2020
e-pub ahead of print date: 19 January 2021
Published date: 19 January 2021
Additional Information:
Funding Information:
The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. Methylation data in the ALSPAC cohort were generated as part of the UK BBSRC funded (BB/I025751/1 and BB/I025263/1) Accessible Resource for Integrated Epigenomic Studies (ARIES, https://www.ariesepigenomics.org.uk ). CLR is supported by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (Grant ref: MC_UU_00011/5). Full details of ALSPAC grant funding can be found on the ALSPAC website ( https://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). The SWS is supported by grants from the Medical Research Council, National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University. Hospital Southampton National Health Service Foundation Trust, and the European Union’s Seventh. Framework Programme (FP7/2007–2013), project EarlyNutrition (grant 289346). Study participants were drawn from a cohort study funded by the Medical Research Council and the Dunhill Medical Trust. This publication is the work of the authors, who will serve as guarantors for the contents of this paper. This research was supported by a BBSRC DTP studentship (Grant ref: BB/M011186/1) at Newcastle University. CLR is supported by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (Grant ref: MC_UU_00011/5). KAL, EA and RM are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone. EA is supported by Diabetes UK (16/0005454). KAL is supported by NIHR Southampton Biomedical Research Centre (IS-BRC-1215–20004)), British Heart Foundation (RG/15/17/3174), and Diabetes UK (16/0005454). KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515–10042) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215–20004)), the European Union (Erasmus + Programme ImpENSA 598488-EPP-1–2018-1-DE-EPPKA2-CBHE-JP), British Heart Foundation (RG/15/17/3174), the US National Institute On Aging of the National Institutes of Health (Award No. U24AG047867) and the UK ESRC and BBSRC (Award No. ES/M00919X/1). KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone. MAH is supported by the British Heart Foundation.
Publisher Copyright:
© 2021, The Author(s).
Keywords:
ALSPAC, Conditional weight gain, DNA methylation, DOHAD, EWAS, Epigenetics, Rapid weight gain, SWS
Identifiers
Local EPrints ID: 444867
URI: http://eprints.soton.ac.uk/id/eprint/444867
ISSN: 1868-7075
PURE UUID: 8a8ba4e0-4ebe-4bcf-b1dd-c57d3bd61ef4
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Date deposited: 06 Nov 2020 17:34
Last modified: 17 Mar 2024 06:01
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Contributors
Author:
N. Robinson
Author:
H. Brown
Author:
Elie Antoun
Author:
Robert Murray
Author:
M.S. Pearce
Author:
C.L. Relton
Author:
V. Albani
Author:
J.A. McKay
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