Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight

Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight

Background: Obesity is a multi-cause chronic disease recognized across the lifespan, with childhood obesity prevalence rising over the past decades. Although exposome-wide association studies have identified early-life environmental drivers of child obesity, and explored the multi-omics signatures o...

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Main Authors: Congrong Wang, Brigitte Reimann, Tim S Nawrot, Dries S Martens, John Wright, Rosemary McEachan, Johanna Lepeule, Wenlun Yuan, Leda Chatzi, Marina Vafeiadi, Regina Grazuleviciene, Sandra Andrusaityte, Oliver Robinson, Jordi Sunyer, Hector Keun, Chung-Ho E. Lau, Alexandros P. Siskos, Muireann Coen, Eva Borràs, Eduard Sabidó, Juan R. González, Marta Vives-Usano, Xavier Estivill, Angel Carracedo, Carlos Ruiz-Arenas, Inés Quintela, Maribel Casas, Mark Nieuwenhuijsen, Ibon Tamayo, Kristine B Gutzkow, Cathrine Thomsen, Amrit K. Sakhi, Mariona Bustamante, Lea Maitre, Martine Vrijheid, Michelle Plusquin, Rossella Alfano
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Environment International
Subjects:
Childhood obesity
Exposome
Multi-omics
Meet-in-the-middle
MOFA
HELIX
Online Access:http://www.sciencedirect.com/science/article/pii/S0160412025003812
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Summary:Background: Obesity is a multi-cause chronic disease recognized across the lifespan, with childhood obesity prevalence rising over the past decades. Although exposome-wide association studies have identified early-life environmental drivers of child obesity, and explored the multi-omics signatures of the exposome of children, it is understudied whether the combined effects of multiple exposures are potentially mediated by multi-omics. Methods: Within the Human Early Life Exposome (HELIX) project, 1041 mother–child pairs were surveyed for a wide range of environmental exposures including over 354 prenatal and childhood exposures. Multi-omics molecular features were measured during childhood, encompassing the blood methylome and transcriptome, plasma proteins and urinary and serum metabolites. Exposome and multi-omics features were integrated into latent factors by Multi-omics Factor Analysis, based on which structural equation modelling was used to assess whether multi-omics mediated associations between exposome and child body mass index (BMI). Results: Key findings included: (i) prenatal nutrition, exercise, and passive smoking influencing BMI via DNA methylation of HOXA5 and Tenascin XB; (ii) childhood exposure to PCBs and phenols linked with BMI through inflammation and coagulation pathways; and (iii) childhood PCB and dietary exposures associated with BMI via immune pathways. Conclusions: This novel untargeted workflow elucidated biological mechanisms linking environmental exposures to child obesity, potentially supporting targeted public health interventions.
ISSN:0160-4120

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