Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium

Background Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism.Methods We analysed associations of infant animal and plant protein intakes with DNA methylation...

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Main Authors: Mohammed El Sharkawy, Janine F. Felix, Veit Grote, Trudy Voortman, Vincent W. V. Jaddoe, Berthold Koletzko, Leanne K. Küpers
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Epigenetics
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Online Access:https://www.tandfonline.com/doi/10.1080/15592294.2023.2299045
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author Mohammed El Sharkawy
Janine F. Felix
Veit Grote
Trudy Voortman
Vincent W. V. Jaddoe
Berthold Koletzko
Leanne K. Küpers
author_facet Mohammed El Sharkawy
Janine F. Felix
Veit Grote
Trudy Voortman
Vincent W. V. Jaddoe
Berthold Koletzko
Leanne K. Küpers
author_sort Mohammed El Sharkawy
collection DOAJ
description Background Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism.Methods We analysed associations of infant animal and plant protein intakes with DNA methylation in early (2−6 years, N = 579) and late (7̄−12 years, N = 604) childhood in two studies. Study-specific robust linear regression models adjusted for relevant confounders were run, and then meta-analysed using a fixed-effects model. We also performed sex-stratified meta-analyses. Follow-up analyses included pathway analysis and eQTM look-up.Results Infant animal protein intake was not associated with DNA methylation in early childhood, but was associated with late-childhood DNA methylation at cg21300373 (P = 4.27 × 10¯8, MARCHF1) and cg10633363 (P = 1.09 × 10¯7, HOXB9) after FDR correction. Infant plant protein intake was associated with early-childhood DNA methylation at cg25973293 (P = 2.26 × 10−7, C1orf159) and cg15407373 (P = 2.13 × 10−7, MBP) after FDR correction. There was no overlap between the findings from the animal and plant protein analyses. We did not find enriched functional pathways at either time point using CpGs associated with animal and plant protein. These CpGs were not previously associated with childhood gene expression. Sex-stratified meta-analyses showed sex-specific DNA methylation associations for both animal and plant protein intake.Conclusion Infant animal protein intake was associated with DNA methylation at two CpGs in late childhood. Infant plant protein intake was associated with DNA methylation in early childhood at two CpGs. A potential mediating role of DNA methylation at these CpGs between infant protein intake and health outcomes requires further investigation.
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spelling doaj-art-b9ef9a33e0904341869d5487313fcb1a2025-08-20T02:20:49ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2023.2299045Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortiumMohammed El Sharkawy0Janine F. Felix1Veit Grote2Trudy Voortman3Vincent W. V. Jaddoe4Berthold Koletzko5Leanne K. Küpers6Division of Metabolic and Nutritional Medicine, Department of Pediatrics, Dr. Von Hauner Children’s Hospital, LMU University Hospital Munich, Munich, GermanyThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsDivision of Metabolic and Nutritional Medicine, Department of Pediatrics, Dr. Von Hauner Children’s Hospital, LMU University Hospital Munich, Munich, GermanyDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsDivision of Metabolic and Nutritional Medicine, Department of Pediatrics, Dr. Von Hauner Children’s Hospital, LMU University Hospital Munich, Munich, GermanyThe Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsBackground Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism.Methods We analysed associations of infant animal and plant protein intakes with DNA methylation in early (2−6 years, N = 579) and late (7̄−12 years, N = 604) childhood in two studies. Study-specific robust linear regression models adjusted for relevant confounders were run, and then meta-analysed using a fixed-effects model. We also performed sex-stratified meta-analyses. Follow-up analyses included pathway analysis and eQTM look-up.Results Infant animal protein intake was not associated with DNA methylation in early childhood, but was associated with late-childhood DNA methylation at cg21300373 (P = 4.27 × 10¯8, MARCHF1) and cg10633363 (P = 1.09 × 10¯7, HOXB9) after FDR correction. Infant plant protein intake was associated with early-childhood DNA methylation at cg25973293 (P = 2.26 × 10−7, C1orf159) and cg15407373 (P = 2.13 × 10−7, MBP) after FDR correction. There was no overlap between the findings from the animal and plant protein analyses. We did not find enriched functional pathways at either time point using CpGs associated with animal and plant protein. These CpGs were not previously associated with childhood gene expression. Sex-stratified meta-analyses showed sex-specific DNA methylation associations for both animal and plant protein intake.Conclusion Infant animal protein intake was associated with DNA methylation at two CpGs in late childhood. Infant plant protein intake was associated with DNA methylation in early childhood at two CpGs. A potential mediating role of DNA methylation at these CpGs between infant protein intake and health outcomes requires further investigation.https://www.tandfonline.com/doi/10.1080/15592294.2023.2299045Epigeneticschildhood DNA methylationanimal proteinearly life nutritionepigenome wide association study
spellingShingle Mohammed El Sharkawy
Janine F. Felix
Veit Grote
Trudy Voortman
Vincent W. V. Jaddoe
Berthold Koletzko
Leanne K. Küpers
Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium
Epigenetics
Epigenetics
childhood DNA methylation
animal protein
early life nutrition
epigenome wide association study
title Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium
title_full Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium
title_fullStr Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium
title_full_unstemmed Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium
title_short Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium
title_sort animal and plant protein intake during infancy and childhood dna methylation a meta analysis in the nutriprogram consortium
topic Epigenetics
childhood DNA methylation
animal protein
early life nutrition
epigenome wide association study
url https://www.tandfonline.com/doi/10.1080/15592294.2023.2299045
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