Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations
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 analy...
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Nature Portfolio
2025-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-94839-9 |
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| author | Tisham De Lachlan Coin Jethro Herberg Michael R Johnson Marjo-Riitta Järvelin |
| author_facet | Tisham De Lachlan Coin Jethro Herberg Michael R Johnson Marjo-Riitta Järvelin |
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| description | 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. |
| format | Article |
| id | doaj-art-7facdb09906144fcaff327b0e10d93d1 |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-7facdb09906144fcaff327b0e10d93d12025-08-20T03:18:32ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-94839-9Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populationsTisham De0Lachlan Coin1Jethro Herberg2Michael R Johnson3Marjo-Riitta Järvelin4Department of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Brain Sciences, Imperial College LondonDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonAbstract 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.https://doi.org/10.1038/s41598-025-94839-9 |
| spellingShingle | Tisham De Lachlan Coin Jethro Herberg Michael R Johnson Marjo-Riitta Järvelin Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations Scientific Reports |
| title | Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations |
| title_full | Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations |
| title_fullStr | Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations |
| title_full_unstemmed | Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations |
| title_short | Plasma metabolomic signatures for copy number variants and COVID-19 risk loci in Northern Finland populations |
| title_sort | plasma metabolomic signatures for copy number variants and covid 19 risk loci in northern finland populations |
| url | https://doi.org/10.1038/s41598-025-94839-9 |
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