Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations
File(s)
Published version
Author(s)
De, Tisham
Coin, Lachlan
Herberg, Jethro
Johnson, Michael R
Jarvelin, Marjo-Riitta
Type
Journal Article
Abstract
Copy number variants (CNVs) are an important class of genomic variation known to be important for human physiology and diseases. Here we present genome-wide metabolomic signatures for CNVs in two Finnish cohorts—The Northern Finland Birth Cohort 1966 (NFBC 1966) and NFBC 1986. We have analysed and reported CNVs in over 9,300 individuals and characterised their dosage effect (CNV-metabolomic QTL) on 228 plasma lipoproteins and metabolites. We have reported reference (normal physiology) metabolomic signatures for up to ~ 2.6 million COVID-19 GWAS results from the National Institutes of Health (NIH) GRASP database, including for outcomes related to COVID-19 death, severity, and hospitalisation. Furthermore, by analysing two exemplar genes for COVID-19 severity namely LZTFL1 and OAS1, we have reported here two additional candidate genes for COVID-19 severity biology, (1) NFIX, a gene related to viral (adenovirus) replication and hematopoietic stem cells and (2) ACSL1, a known candidate gene for sepsis and bacterial inflammation. Based on our results and current literature we hypothesise that (1) charge imbalance across the cellular membrane between cations (Fe2+, Mg2+ etc.) and anions (e.g. ROS, hydroxide ion from cellular Fenton reactions, superoxide etc.), (2) iron trafficking within and between different cell types e.g., macrophages and (3) systemic oxidative stress response (e.g. lipid peroxidation mediated inflammation), together could be of relevance in severe COVID-19 cases. To conclude, our unique atlas of univariate and multivariate metabolomic signatures for CNVs (~ 7.2 million signatures) with deep annotations of various multi-omics data sets provide an important reference knowledge base for human metabolism and diseases.
Date Issued
2025-04-16
Date Acceptance
2025-03-17
Citation
Scientific Reports, 2025, 15
ISSN
2045-2322
Publisher
Nature Portfolio
Journal / Book Title
Scientific Reports
Volume
15
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41598-025-94839-9
Publication Status
Published
Article Number
13172
Date Publish Online
2025-04-16