Pathway level metabolomics analysis identifies carbon metabolism as a key factor of incident hypertension in the Estonian Biobank

The purpose of this study was to find metabolic changes associated with incident hypertension in the volunteer-based Estonian Biobank. We used a subcohort of the Estonian Biobank where metabolite levels had been measured by mass-spectrometry (LC-MS, Metabolon platform). We divided annotated metaboli...

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Bibliographic Details
Published in:Scientific reports Vol. 15; no. 1; pp. 8470 - 13
Main Authors: Hiie, Liis, Kolde, Anastassia, Pervjakova, Natalia, Reigo, Anu, Abner, Erik, Võsa, Urmo, Esko, Tõnu, Fischer, Krista, Palta, Priit, Kronberg, Jaanika
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12.03.2025
Nature Publishing Group
Nature Portfolio
Subjects:
631/1647/320
692/699/75/243
Adult
Aged
Biobank
Biobanks
Biological Specimen Banks
Body Mass Index
Carbon
Carbon - metabolism
Case-Control Studies
Data-driven
Datasets
Electronic medical records
Estonia - epidemiology
Female
Humanities and Social Sciences
Humans
Hypertension
Hypertension - epidemiology
Hypertension - metabolism
Incidence
Incident disease
Male
Metabolic Networks and Pathways
Metabolism
Metabolites
Metabolomics
Metabolomics - methods
Middle Aged
multidisciplinary
Pathways
Principal components analysis
Science
Science (multidisciplinary)
Spectrometry
Estonia
Hypertension
Metabolomics
Data-driven
Pathways
Biobank
Incident disease
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:The purpose of this study was to find metabolic changes associated with incident hypertension in the volunteer-based Estonian Biobank. We used a subcohort of the Estonian Biobank where metabolite levels had been measured by mass-spectrometry (LC-MS, Metabolon platform). We divided annotated metabolites of 989 individuals into KEGG pathways, followed by principal component analysis of metabolites in each pathway, resulting in a dataset of 91 pathway components. Next, we defined incident hypertension cases and controls based on electronic health records, resulting in a dataset of 101 incident hypertension cases and 450 controls. We used Cox proportional hazards models and replicated the results in a separate cohort of the Estonian Biobank, assayed with LC-MS dataset of the Broad platform and including 582 individuals. Our results show that body mass index and a component of the carbon metabolism KEGG pathway are associated with incident hypertension in both discovery and replication cohorts. We demonstrate that a high-dimensional dataset can be meaningfully reduced into informative pathway components that can subsequently be analysed in an interpretable way, and replicated in a metabolomics dataset from a different platform.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-025-92840-w