Advancing translational exposomics: bridging genome, exposome and personalized medicine

Understanding the interplay between genetic predisposition and environmental and lifestyle exposures is essential for advancing precision medicine and public health. The exposome, defined as the sum of all environmental exposures an individual encounters throughout their lifetime, complements genomic data by elucidating how external and internal exposure factors influence health outcomes. This treatise highlights the emerging discipline of translational exposomics that integrates exposomics and genomics, offering a comprehensive approach to decipher the complex relationships between environmental and lifestyle exposures, genetic variability, and disease phenotypes. We highlight cutting-edge methodologies, including multi-omics technologies, exposome-wide association studies (EWAS), physiology-based biokinetic modeling, and advanced bioinformatics approaches. These tools enable precise characterization of both the external and the internal exposome, facilitating the identification of biomarkers, exposure-response relationships, and disease prediction and mechanisms. We also consider the importance of addressing socio-economic, demographic, and gender disparities in environmental health research. We emphasize how exposome data can contextualize genomic variation and enhance causal inference, especially in studies of vulnerable populations and complex diseases. By showcasing concrete examples and proposing integrative platforms for translational exposomics, this work underscores the critical need to bridge genomics and exposomics to enable precision prevention, risk stratification, and public health decision-making. This integrative approach offers a new paradigm for understanding health and disease beyond genetics alone.