Multi-omics signatures of the human early life exposome
Léa Maître, Mariona Bustamante, Carles Hernandéz-Ferrer, Denise Thiel, Chung‐Ho E. Lau, Alexandros Siskos, Marta Vives-Usano, Carlos Ruiz-Arenas, Dolors Pelegrí-Sisó, Oliver Robinson, Dan Mason, John Wright, Solène Cadiou, Rémy Slama, Barbara Heude, Maribel Casas, Jordi Sunyer, Eleni Papadopoulou, Kristine B. Gützkow, Sandra Andrušaitytė, Regina Gražulevičienė, Marina Vafeiadi, Leda Chatzi, Amrit Kaur Sakhi, Cathrine Thomsen, Ibón Tamayo, Mark Nieuwenhuijsen, José Urquiza, Eva Borràs, Eduard Sabidó, Inés Quintela, Ãngel Carracedo, Xavier Estivill, Muireann Coen, Juan R. González, Hector C. Keun, Martine Vrijheid
Abstract
Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting of >100 chemical, outdoor, social and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, proteins and metabolites) in childhood. We identify 1170 associations, 249 in pregnancy and 921 in childhood, which reveal potential biological responses and sources of exposure. Pregnancy exposures, including maternal smoking, cadmium and molybdenum, are predominantly associated with child DNA methylation changes. In contrast, childhood exposures are associated with features across all omics layers, most frequently the serum metabolome, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions, among others. Our comprehensive and unique resource of all associations ( https://helixomics.isglobal.org/ ) will serve to guide future investigation into the biological imprints of the early life exposome.