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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
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
1868-7075
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.
fbe77a7c-2e53-421f-8fc8-37250ce9e867
Albani, V.
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McKay, J.A.
977c9491-b4e2-4507-9cd9-9c0adc2cae2b
Robinson, N.
2153253d-f40c-46ba-a96a-8dc1aa952d4c
Brown, H.
127d80f2-c65b-4622-9bb0-31861ec75b4d
Antoun, Elie
10fc5678-b33c-4410-977d-b11234031791
Godfrey, Keith
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Hanson, Mark
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Crozier, Sarah
9c3595ce-45b0-44fa-8c4c-4c555e628a03
Murray, Robert
c3e973b5-525c-49b3-96ee-af60a666a0f4
Pearce, M.S.
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Relton, C.L.
fbe77a7c-2e53-421f-8fc8-37250ce9e867
Albani, V.
77deebfb-701a-4bc9-97fa-c56ee6fff3ed
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 (8), [8]. (doi:10.1186/s13148-020-00952-z).

Record type: Article

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

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ALSPAC paper -accepted pre-formatted 21-10-20 - Accepted Manuscript
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Accepted/In Press date: 16 October 2020
e-pub ahead of print date: 19 January 2021
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
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Mark Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Sarah Crozier: ORCID iD orcid.org/0000-0002-9524-1127

Catalogue record

Date deposited: 06 Nov 2020 17:34
Last modified: 12 Mar 2021 05:01

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Contributors

Author: N. Robinson
Author: H. Brown
Author: Elie Antoun
Author: Keith Godfrey ORCID iD
Author: Mark Hanson ORCID iD
Author: Karen Lillycrop ORCID iD
Author: Sarah Crozier ORCID iD
Author: Robert Murray
Author: M.S. Pearce
Author: C.L. Relton
Author: V. Albani
Author: J.A. McKay

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