Integrating Multi-Omics with environmental data for precision health: A novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease
Share:
Abstract
Background
Precision Health aims to revolutionize disease prevention by leveraging information across multiple omic datasets (multi-omics). However, existing methods generally do not consider personalized environmental risk factors (e.g., environmental pollutants).
Objective
To develop and apply a precision health framework which combines multiomic integration (including early, intermediate, and late integration, representing sequential stages at which omics layers are combined for modeling) with mediation approaches (including high-dimensional mediation to identify biomarkers, mediation with latent factors to identify pathways, and integrated/quasi-mediation to identify high-risk subpopulations) to identify novel biomarkers of prenatal mercury induced metabolic dysfunction-associated fatty liver disease (MAFLD), elucidate molecular pathways linking prenatal mercury with MAFLD in children, and identify high-risk children based on integrated exposure and multiomics data.
Methods
This prospective cohort study used data from 420 mother–child pairs from the Human Early Life Exposome (HELIX) project. Mercury concentrations were determined in maternal or cord blood from pregnancy. Cytokeratin 18 (CK-18; a MAFLD biomarker) and five omics layers (DNA Methylation, gene transcription, microRNA, proteins, and metabolites) were measured in blood in childhood (age 6–10 years).
Results
Each standard deviation increase in prenatal mercury was associated with a 0.11 [95% confidence interval: 0.02–0.21] standard deviation increase in CK-18. High dimensional mediation analysis identified 10 biomarkers linking prenatal mercury and CK-18, including six CpG sites and four transcripts. Mediation with latent factors identified molecular pathways linking mercury and MAFLD, including altered cytokine signaling and hepatic stellate cell activation. Integrated/quasi-mediation identified high risk subgroups of children based on unique combinations of exposure levels, omics profiles (driven by epigenetic markers), and MAFLD.
Conclusions
Prenatal mercury exposure is associated with elevated liver enzymes in childhood, likely through alterations in DNA methylation and gene expression. Our analytic framework can be applied across many different fields and serve as a resource to help guide future precision health investigations.
References: Jesse A. Goodrich, Hongxu Wang, Qiran Jia, Nikos Stratakis, Yinqi Zhao, Léa Maitre, Mariona Bustamante, Marina Vafeiadi, Max Aung, Sandra Andrušaitytė, Xavier Basagana, Shohreh F. Farzan, Barbara Heude, Hector Keun, Rob McConnell, Tiffany C. Yang, Alexandros P. Siskos, Jose Urquiza, Damaskini Valvi, Nerea Varo, Line Småstuen Haug, Bente M. Oftedal, Regina Gražulevičienė, Claire Philippat, John Wright, Martine Vrijheid, Leda Chatzi, David V. Conti,Integrating Multi-Omics with environmental data for precision health: A novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease,
Environment International,
Volume 190,
2024,
108930,
ISSN 0160-4120,
https://doi.org/10.1016/j.envint.2024.108930.
Details:
Theme:
Author(s):
Jesse A. Goodrich, Hongxu Wang, Qiran Jia, Nikos Stratakis, Yinqi Zhao, Léa Maitre b c d, Mariona Bustamante,
Marina Vafeiadi, Max Aung, Sandra Andrušaitytė, Xavier Basagana, Shohreh F. Farzan ,Barbara Heude ,Hector Keun, Rob McConnell , Tiffany C. Yang , Alexandros P. Siskos , Jose Urquiza , Damaskini Valvi , Nerea Varo , Line Småstuen Haug , Bente M. Oftedal , Regina Gražulevičienė , Claire Philippat , John Wright , Martine Vrijheid , Leda Chatzi,David V. Conti
Director
Principal Research Fellow
