The University of Southampton
University of Southampton Institutional Repository

Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children

Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children
Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children
Background: Breastfeeding is protective against many long-term diseases, yet the mechanisms involved are unknown. Leptin gene (LEP) is reported to be associated with body mass index (BMI). On the other hand, breastfeeding duration has been found to be associated with DNA methylation (DNAm) of the LEP gene. Therefore, epigenetic regulation of LEP may represent the mechanism underlying the protective effect of breastfeeding duration against obesity.Methods: In the Isle of Wight Birth Cohort, peripheral blood DNAm at 23 cytosine-phosphate-guanine sites (CpGs) in the LEP locus in 10-year-old (n = 297) samples and 16 CpGs in 18-year-old (n = 305) samples, were generated using the Illumina Infinium MethylationEPIC and HumanMethylation450 Beadchips respectively and tested for association with breastfeeding duration (total and exclusive) using linear regression. To explore the association between breastfeeding durations and genome-wide DNAm, epigenome-wide association studies (EWASs) and differential methylation region (DMR) analyses were performed. BMI trajectories spanning the first 18 years of life were used as the outcome to test the association with breastfeeding duration (exposure) using multi-nominal logistic regression. Mediation analysis was performed for significant CpG sites.Results: Both total and exclusive breastfeeding duration were associated with DNAm at four LEP CpG sites at 10 years (P value < 0.05), and not at 18 years. Though no association was observed between breastfeeding duration and genome-wide DNAm, DMR analyses identified five significant differentially methylated regions (Sidak adjusted P value < 0.05). Breastfeeding duration was also associated with the early transient overweight trajectory. Furthermore, DNAm of LEP was associated with this trajectory at one CpG site and early persistent obesity at another, though mediation analysis was not significant.Conclusions: Breastfeeding duration is associated with LEP methylation at age 10 years and BMI trajectory. LEP DNAm is also significantly associated with BMI trajectories throughout childhood, though sample sizes were small. However, mediation analysis did not demonstrate that DNAm of LEP explained the protective effect of breastfeeding against childhood obesity.
1868-7075
128
Sherwood, William B.
49cd2f0d-ef0c-4b2a-88e3-02915058f28f
Bion, Victoria
ed3bace5-ebdf-4725-839a-cf1a9feb00db
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Soto-ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Kurukulaaratchy, Ramesh J.
9c7b8105-2892-49f2-8775-54d4961e3e74
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338
Sherwood, William B.
49cd2f0d-ef0c-4b2a-88e3-02915058f28f
Bion, Victoria
ed3bace5-ebdf-4725-839a-cf1a9feb00db
Lockett, Gabrielle A.
4d92a28c-f54c-431b-81f6-e82ad9057d7a
Ziyab, Ali H.
12905e44-3fd1-47c2-98e5-35320e89815b
Soto-ramírez, Nelís
3526295b-e2ec-4cf3-bc74-088d10943f45
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Kurukulaaratchy, Ramesh J.
9c7b8105-2892-49f2-8775-54d4961e3e74
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Rezwan, Faisal I.
203f8f38-1f5d-485b-ab11-c546b4276338

Sherwood, William B., Bion, Victoria, Lockett, Gabrielle A., Ziyab, Ali H., Soto-ramírez, Nelís, Mukherjee, Nandini, Kurukulaaratchy, Ramesh J., Ewart, Susan, Zhang, Hongmei, Arshad, Syed, Karmaus, Wilfried, Holloway, John W. and Rezwan, Faisal I. (2019) Duration of breastfeeding is associated with leptin (LEP) DNA methylation profiles and BMI in 10-year-old children. Clinical Epigenetics, 11 (1), 128. (doi:10.1186/s13148-019-0727-9).

Record type: Article

Abstract

Background: Breastfeeding is protective against many long-term diseases, yet the mechanisms involved are unknown. Leptin gene (LEP) is reported to be associated with body mass index (BMI). On the other hand, breastfeeding duration has been found to be associated with DNA methylation (DNAm) of the LEP gene. Therefore, epigenetic regulation of LEP may represent the mechanism underlying the protective effect of breastfeeding duration against obesity.Methods: In the Isle of Wight Birth Cohort, peripheral blood DNAm at 23 cytosine-phosphate-guanine sites (CpGs) in the LEP locus in 10-year-old (n = 297) samples and 16 CpGs in 18-year-old (n = 305) samples, were generated using the Illumina Infinium MethylationEPIC and HumanMethylation450 Beadchips respectively and tested for association with breastfeeding duration (total and exclusive) using linear regression. To explore the association between breastfeeding durations and genome-wide DNAm, epigenome-wide association studies (EWASs) and differential methylation region (DMR) analyses were performed. BMI trajectories spanning the first 18 years of life were used as the outcome to test the association with breastfeeding duration (exposure) using multi-nominal logistic regression. Mediation analysis was performed for significant CpG sites.Results: Both total and exclusive breastfeeding duration were associated with DNAm at four LEP CpG sites at 10 years (P value < 0.05), and not at 18 years. Though no association was observed between breastfeeding duration and genome-wide DNAm, DMR analyses identified five significant differentially methylated regions (Sidak adjusted P value < 0.05). Breastfeeding duration was also associated with the early transient overweight trajectory. Furthermore, DNAm of LEP was associated with this trajectory at one CpG site and early persistent obesity at another, though mediation analysis was not significant.Conclusions: Breastfeeding duration is associated with LEP methylation at age 10 years and BMI trajectory. LEP DNAm is also significantly associated with BMI trajectories throughout childhood, though sample sizes were small. However, mediation analysis did not demonstrate that DNAm of LEP explained the protective effect of breastfeeding against childhood obesity.

Text
Breastfeeding_Lep_DNAm_BMI_Sherwood_etal - Accepted Manuscript
Download (953kB)
Text
Duration of breastfeeding - Version of Record
Available under License Creative Commons Attribution.
Download (696kB)

More information

e-pub ahead of print date: 29 August 2019
Published date: 1 December 2019

Identifiers

Local EPrints ID: 434044
URI: https://eprints.soton.ac.uk/id/eprint/434044
ISSN: 1868-7075
PURE UUID: 75fece31-2558-43e1-adbf-a7ecbe791a7f
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X

Catalogue record

Date deposited: 11 Sep 2019 16:30
Last modified: 03 Dec 2019 01:58

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×