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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2025-08-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Congrong Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4de10a4c36f842d19b41eca9aa1de6ce |
| institution | Kabale University |
| issn | 0160-4120 |
| language | English |
| publishDate | 2025-08-01 |
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| series | Environment International |
| spelling | doaj-art-4de10a4c36f842d19b41eca9aa1de6ce2025-08-20T03:32:47ZengElsevierEnvironment International0160-41202025-08-0120210963010.1016/j.envint.2025.109630Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweightCongrong Wang0Brigitte Reimann1Tim S Nawrot2Dries S Martens3John Wright4Rosemary McEachan5Johanna Lepeule6Wenlun Yuan7Leda Chatzi8Marina Vafeiadi9Regina Grazuleviciene10Sandra Andrusaityte11Oliver Robinson12Jordi Sunyer13Hector Keun14Chung-Ho E. Lau15Alexandros P. Siskos16Muireann Coen17Eva Borràs18Eduard Sabidó19Juan R. González20Marta Vives-Usano21Xavier Estivill22Angel Carracedo23Carlos Ruiz-Arenas24Inés Quintela25Maribel Casas26Mark Nieuwenhuijsen27Ibon Tamayo28Kristine B Gutzkow29Cathrine Thomsen30Amrit K. Sakhi31Mariona Bustamante32Lea Maitre33Martine Vrijheid34Michelle Plusquin35Rossella Alfano36Centre for Environmental Health, Hasselt University, BelgiumCentre for Environmental Health, Hasselt University, BelgiumCentre for Environmental Health, Hasselt University, Belgium; Department of Public Health & Primary Care, Leuven University, Leuven, BelgiumCentre for Environmental Health, Hasselt University, BelgiumBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UKBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UKUniversité Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institut pour l'Avancée des Biosciences (IAB), Team of Environmental Epidemiology Applied to Development and Respiratory Health, 38000 GRENOBLE, FranceUniversité Grenoble Alpes, INSERM U1209, CNRS UMR 5309, Institut pour l'Avancée des Biosciences (IAB), Team of Environmental Epidemiology Applied to Development and Respiratory Health, 38000 GRENOBLE, FranceDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USADepartment of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, GreeceDepartment of Environmental Sciences, Vytautas Magnus University, Kaunas, LithuaniaDepartment of Environmental Sciences, Vytautas Magnus University, Kaunas, LithuaniaMRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UKInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, SpainDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Cancer Metabolism & Systems Toxicology Group, Division of Cancer, Department of Surgery & Cancer, Imperial College London, London, UKMRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK; Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UKCancer Metabolism & Systems Toxicology Group, Division of Cancer, Department of Surgery & Cancer, Imperial College London, London, UKDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UKUniversitat Pompeu Fabra (UPF), Barcelona, Spain; Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, SpainUniversitat Pompeu Fabra (UPF), Barcelona, Spain; Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, SpainInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, SpainInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, SpainCenter for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, SpainMedicine Genomics Group, Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER-ISCIII), University of Santiago de Compostela, CIMUS, Santiago de Compostela, Spain; Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Servicio Gallego de Salud (SERGAS), Santiago de Compostela, Galicia, SpainComputational Biology Program, CIMA University of Navarra, Pamplona 31008, SpainMedicine Genomics Group, Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER-ISCIII), University of Santiago de Compostela, CIMUS, Santiago de Compostela, SpainInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, SpainInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, SpainComputational Biology Program, CIMA University of Navarra, Pamplona 31008, SpainDivision of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayDivision of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayDivision of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, NorwayInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, SpainInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, SpainInstitute for Global Health (ISGlobal), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, SpainCentre for Environmental Health, Hasselt University, BelgiumCentre for Environmental Health, Hasselt University, Belgium; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S0160412025003812Childhood obesityExposomeMulti-omicsMeet-in-the-middleMOFAHELIX |
| spellingShingle | 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 Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight Environment International Childhood obesity Exposome Multi-omics Meet-in-the-middle MOFA HELIX |
| title | Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight |
| title_full | Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight |
| title_fullStr | Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight |
| title_full_unstemmed | Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight |
| title_short | Meet-in-the-middle meets multi-omics identifying molecular signatures of environmental drivers of childhood overweight |
| title_sort | meet in the middle meets multi omics identifying molecular signatures of environmental drivers of childhood overweight |
| topic | Childhood obesity Exposome Multi-omics Meet-in-the-middle MOFA HELIX |
| url | http://www.sciencedirect.com/science/article/pii/S0160412025003812 |
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