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Science. 2018 Aug 24;361(6404):769-773. doi: 10.1126/science.aaq1327. Epub 2018 Aug 2.

Co-regulatory networks of human serum proteins link genetics to disease.

Author information

1
Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland. valur@hjarta.is v.gudnason@hjarta.is jlamb@gnf.org.
2
Faculty of Pharmacology, University of Iceland, 101 Reykjavik, Iceland.
3
Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland.
4
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. valur@hjarta.is v.gudnason@hjarta.is jlamb@gnf.org.
5
Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA 02139, USA.
6
Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
7
Centre of Public Health Sciences, University of Iceland, 101 Reykjavik, Iceland.
8
Department of Integrative Biology and Physiology, University of California, Los Angeles CA, USA.
9
School of Science and Engineering, Mentavegur 1, IS-101, Reykjavik University, 101 Reykjavik, Iceland.
10
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
11
Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892-9205, USA.
12
Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
#
Contributed equally

Abstract

Proteins circulating in the blood are critical for age-related disease processes; however, the serum proteome has remained largely unexplored. To this end, 4137 proteins covering most predicted extracellular proteins were measured in the serum of 5457 Icelanders over 65 years of age. Pairwise correlation between proteins as they varied across individuals revealed 27 different network modules of serum proteins, many of which were associated with cardiovascular and metabolic disease states, as well as overall survival. The protein modules were controlled by cis- and trans-acting genetic variants, which in many cases were also associated with complex disease. This revealed co-regulated groups of circulating proteins that incorporated regulatory control between tissues and demonstrated close relationships to past, current, and future disease states.

PMID:
30072576
PMCID:
PMC6190714
DOI:
10.1126/science.aaq1327
[Indexed for MEDLINE]
Free PMC Article

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