Co-regulatory networks of human serum proteins link genetics to disease
Open accessAbstract
The blood proteome in disease: Understanding the function of human blood serum proteins in disease has been limited by difficulties in monitoring their production, accumulation, and distribution. Emilsson et al. investigated human serum proteins of more than 5000 Icelanders over the age of 65. The composition of blood serum includes a complex regulatory network of proteins that are globally coordinated across most or all tissues. The authors identified modules and functional groups associated with disease and health outcomes and were able to link genetic variants to complex diseases. Science , this issue p. 769
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The pleiotropic loci included well-established, previously identified pleiotropic loci such as MHC, ABO, ZFPM2, ARHGEF3, GCKR, SERPINA1, SH2B3 and ASGR1.
“These included well-established, previously identified [17][18][19][20] pleiotropic loci such as MHC, ABO, ZFPM2, ARHGEF3, GCKR, SERPINA1, SH2B3 and ASGR1”
From Plasma proteomic associations with genetics and health in the UK Biobank (2023) · cites this paper as [17]
The section “Genetic variants influence serum protein levels” explicitly describes pleiotropy at ABO as well established. Our copy does not identify MHC, ZFPM2, ARHGEF3, GCKR, SERPINA1, SH2B3, or ASGR1 as previously identified pleiotropic loci, so it supports only part of the list. (LLM, conf=0.86)
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- Authors
- Emilsson, V., Ilkov, M., Lamb, J. R., Finkel, N., Gudmundsson, E. F., Pitts, R., Hoover, H., Gudmundsdottir, V., Horman, S. R., Aspelund, T., Shu, L., Trifonov, V., Sigurdsson, S., Manolescu, A., Zhu, J., Olafsson, Ö., Jakobsdottir, J., Lesley, S. A., To, J., Zhang, J., Harris, T. B., Launer, L. J., Zhang, B., Eiriksdottir, G., Yang, X., Orth, A. P., Jennings, L. L., & Gudnason, V.
- Affiliations
- University of Iceland (IS)
- Icelandic Heart Association (IS)
- Genomics Institute of the Novartis Research Foundation (US)
- Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA 02139, USA.
- Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland.
- University of California, Los Angeles (US)
- Reykjavík University (IS)
- Icahn School of Medicine at Mount Sinai (US)
- National Institutes of Health (US)
- Corresponding author
- Emilsson, Valur
- Ilkov, Marjan
- Lamb, John R.
- Jennings, Lori L.
- Gudnason, Vilmundur
- ORCID
- Emilsson, Valur
- Ilkov, Marjan
- Lamb, John R.
- Finkel, Nancy
- Gudmundsson, Elias F.
- Pitts, Rebecca
- Hoover, Heather
- Gudmundsdottir, Valborg
- Horman, Shane R.
- Aspelund, Thor
- Shu, Le
- Trifonov, Vladimir
- Sigurdsson, Sigurdur
- Manolescu, Andrei
- Zhu, Jun
- Lesley, Scott A.
- To, Jeremy
- Zhang, Jia
- Harris, Tamara B.
- Launer, Lenore J.
- Zhang, Bin
- Yang, Xia
- Orth, Anthony P.
- Jennings, Lori L.
- Gudnason, Vilmundur
- Venue
- Science
- Published
- 2018-08-24
- Volume
- 361
- Issue
- 6404
- Pages
- 769-773
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6190714
- OpenAlex
- W2885870007
- Cited by
- 680
- References
- 12
- Citations by year
- 2026: 72 · 2025: 121 · 2024: 114 · 2023: 77 · 2022: 74 · 2021: 98 · 2020: 83 · 2019: 35 · 2018: 6
- FWCI
- 19.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK104363)
- National Institute of Neurological Disorders and Stroke (NS103088)
- Fondation Leducq
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- serum proteome, protein modules, aging, cardiovascular disease, metabolic disorders, overall survival, genetic variants, cis-acting regulation, trans-acting regulation, extracellular proteins, Icelanders, age-related diseases
- MeSH terms
- Blood Proteins, Cardiovascular Diseases, Humans, Iceland, Metabolic Diseases, Genetic Variation, Genetic Predisposition to Disease, Proteome, Proteomics, Aptamers, Nucleotide, Metabolic Networks and Pathways
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