Multi-omics approaches for understanding gene-environment interactions in noncommunicable diseases: techniques, translation, and equity issues

Abstract Non-communicable diseases (NCDs) such as cardiovascular diseases, chronic respiratory diseases, cancers, diabetes, and mental health disorders pose a significant global health challenge, accounting for the majority of fatalities and disability-adjusted life years worldwide. These diseases arise from the complex interactions between genetic, behavioral, and environmental factors, necessitating a thorough understanding of these dynamics to identify effective diagnostic strategies and interventions. Although recent advances in multi-omics technologies have greatly enhanced our ability to explore these interactions, several challenges remain. These challenges include the inherent complexity and heterogeneity of multi-omic datasets, limitations in analytical approaches, and severe underrepresentation of non-European genetic ancestries in most omics datasets, which restricts the generalizability of findings and exacerbates health disparities. This scoping review evaluates the global landscape of multi-omics data related to NCDs from 2000 to 2024, focusing on recent advancements in multi-omics data integration, translational applications, and equity considerations. We highlight the need for standardized protocols, harmonized data-sharing policies, and advanced approaches such as artificial intelligence/machine learning to integrate multi-omics data and study gene-environment interactions. We also explore challenges and opportunities in translating insights from gene-environment (GxE) research into precision medicine strategies. We underscore the potential of global multi-omics research in advancing our understanding of NCDs and enhancing patient outcomes across diverse and underserved populations, emphasizing the need for equity and fairness-centered research and strategic investments to build local capacities in underrepresented populations and regions.