TY - JOUR
T1 - A meta-analysis of epigenome-wide association studies of ultra-processed food consumption with DNA methylation in European children
AU - Llauradó-Pont, Joana
AU - Stratakis, Nikos
AU - Fiorito, Giovanni
AU - Handakas, Evangelos
AU - Neumann, Alexander
AU - Barros, Henrique
AU - Brantsæter, Anne Lise
AU - Chang, Kiara
AU - Chatzi, Leda
AU - Felix, Janine F.
AU - Grazuleviciene, Regina
AU - Jaddoe, Vincent W.V.
AU - Karachaliou, Marianna
AU - Lecorguillé, Marion
AU - Lopes, Carla
AU - Millett, Christopher
AU - McEachan, Rosemary R.C.
AU - Papadopoulou, Eleni
AU - Slama, Remy
AU - Vamos, Eszter P.
AU - Vineis, Paolo
AU - Vrijheid, Martine
AU - Wright, John
AU - Voortman, Trudy
AU - Bustamante, Mariona
AU - Robinson, Oliver
AU - Lassale, Camille
N1 - Funding Information:
We are grateful to participants in all cohorts included in the four studies (HELIX, Generation XXI, ALSPAC and Generation R) across countries who have generously given their time and collaborated in the studies. The HELIX cohort received funding from the European Community\u2019s Seventh Framework Programme (FP7/2007\u20132013) [grant number 308333]. Joana Llaurad\u00F3-Pont has received support from the European Union\u2014NextGenerationEU and the Spanish government, under the Investigo Programme (grant ID: 2022 INV-1 00046). Camille Lassale is supported by a Ramon y Cajal Fellowship RYC2020-029599 funded by MICIU/AEI/ https://doi.org/10.13039/501100011033 and the European Social Fund 'Invest in your future'. Nikos Stratakis has been supported from the European Union\u2019s Horizon Europe research and innovation programme under the Marie Sk\u0142odowska-Curie Actions (MSCA) Postdoctoral Fellowships (grant ID: 101059245), from the Ministry of Science and Innovation and State Research Agency through the 'Centro de Excelencia Severo Ochoa 2019\u20132023' Program (CEX2018-000806-S) and by a Juan de la Cierva-Incorporaci\u00F3n fellowship (IJC2020-043630-I) financed by Ministerio de Ciencia e Innovaci\u00F3n (MCIN)/Agencia Estatal de Investigaci\u00F3n (AEI)/ https://doi.org/10.13039/501100011033 and the European Union 'NextGenerationEU/PRTR'. Oliver Robinson was supported by a UKRI Future Leaders Fellowship (MR/S03532X/1). This work received funding from the European Union\u2019s Horizon 2020 research and innovation programme (774548, STOP; 874739, LongITools; 874583, EUCAN-Connect) and from the European Joint Programming Initiative 'A Healthy Diet for a Healthy Life' (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022 and PREcisE project ZonMw the Netherlands no.529051023). Details of funding for each study and for contributions of individual studies can be found in Supplementary material S3 . No funders listed here or in Supplementary material S3 influenced the study aim, design, analysis or interpretation of results. The results expressed here are those of the authors and not necessarily any listed funder.
Publisher Copyright:
© The Author(s) 2024.
PY - 2025/12
Y1 - 2025/12
N2 - Background/objective: There is limited knowledge on how diet affects the epigenome of children. Ultra-processed food (UPF) consumption is emerging as an important factor impacting health, but mechanisms need to be uncovered. We therefore aimed to assess the association between UPF consumption and DNA methylation in children. Methods: We conducted a meta-analysis of epigenome-wide association studies (EWAS) from a total of 3152 children aged 5–11 years from four European studies (HELIX, Generation XXI, ALSPAC, and Generation R). UPF consumption was defined applying the Nova food classification system (group 4), and DNA methylation was measured in blood with Illumina Infinium Methylation arrays. Associations were estimated within each cohort using robust linear regression models, adjusting for relevant covariates, followed by a meta-analysis of the resulting EWAS estimates. Results: Although no CpG was significant at FDR level, we found suggestive associations (p-value < 10–5) between UPF consumption and methylation at seven CpG sites. Three of them, cg00339913 (PHYHIP), cg03041696 (intergenic), and cg03999434 (intergenic), were negatively associated, whereas the other four, cg14665028 (NHEJ1), cg18968409 (intergenic), cg24730307 (intergenic), and cg09709951 (ATF7), were positively associated with UPF intake. These CpGs have been previously associated with health outcomes such as carcinomas, and the related genes are mainly involved in pathways related to thyroid hormones and liver function. Conclusion: We only found suggestive changes in methylation at 7 CpGs associated with UPF intake in a large EWAS among children: although this shows a potential impact of UPF intake on DNAm, this might not be a key mechanism underlying the health effects of UPFs in children. There is a need for more detailed dietary assessment in children studies and of intervention studies to assess potential epigenetic changes linked to a reduction in UPF in the diet.
AB - Background/objective: There is limited knowledge on how diet affects the epigenome of children. Ultra-processed food (UPF) consumption is emerging as an important factor impacting health, but mechanisms need to be uncovered. We therefore aimed to assess the association between UPF consumption and DNA methylation in children. Methods: We conducted a meta-analysis of epigenome-wide association studies (EWAS) from a total of 3152 children aged 5–11 years from four European studies (HELIX, Generation XXI, ALSPAC, and Generation R). UPF consumption was defined applying the Nova food classification system (group 4), and DNA methylation was measured in blood with Illumina Infinium Methylation arrays. Associations were estimated within each cohort using robust linear regression models, adjusting for relevant covariates, followed by a meta-analysis of the resulting EWAS estimates. Results: Although no CpG was significant at FDR level, we found suggestive associations (p-value < 10–5) between UPF consumption and methylation at seven CpG sites. Three of them, cg00339913 (PHYHIP), cg03041696 (intergenic), and cg03999434 (intergenic), were negatively associated, whereas the other four, cg14665028 (NHEJ1), cg18968409 (intergenic), cg24730307 (intergenic), and cg09709951 (ATF7), were positively associated with UPF intake. These CpGs have been previously associated with health outcomes such as carcinomas, and the related genes are mainly involved in pathways related to thyroid hormones and liver function. Conclusion: We only found suggestive changes in methylation at 7 CpGs associated with UPF intake in a large EWAS among children: although this shows a potential impact of UPF intake on DNAm, this might not be a key mechanism underlying the health effects of UPFs in children. There is a need for more detailed dietary assessment in children studies and of intervention studies to assess potential epigenetic changes linked to a reduction in UPF in the diet.
KW - Children
KW - DNA methylation
KW - Epigenome-wide association study (EWAS)
KW - Nutrition
KW - Ultra-processed food (UPF)
UR - https://www.scopus.com/pages/publications/85214247681
U2 - 10.1186/s13148-024-01782-z
DO - 10.1186/s13148-024-01782-z
M3 - Article
C2 - 39773758
AN - SCOPUS:85214247681
SN - 1868-7075
VL - 17
JO - Clinical Epigenetics
JF - Clinical Epigenetics
IS - 1
M1 - 3
ER -
SDG 3 Good Health and Well-being