Integrating Multi-Omics with environmental data for precision health: a novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease
File(s)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2024-08-01
Date Acceptance
2024-07-31
Citation
Environment International, 2024, 190
ISSN
0160-4120
Publisher
Elsevier
Journal / Book Title
Environment International
Volume
190
Copyright Statement
© 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Commission of the European Communities
Commission of the European Communities
Identifier
10.1016/j.envint.2024.108930
Grant Number
874583
308333
Subjects
Bioinformatics
Biomarkers
CHILDREN
Environmental Sciences
Environmental Sciences & Ecology
Epigenetics
EXPOSOME
JOINT
Life Sciences & Biomedicine
MEDIATION ANALYSIS
MODEL
Multiomics
Precision health
Prenatal exposures
Science & Technology
SELECTION
Publication Status
Published
Article Number
108930
Date Publish Online
2024-08-03