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

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 correl...

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Published in:Science (American Association for the Advancement of Science) Vol. 361; no. 6404; p. 769
Main Authors: 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, Olafsson, Örn, Jakobsdottir, Johanna, Lesley, Scott A, To, Jeremy, Zhang, Jia, Harris, Tamara B, Launer, Lenore J, Zhang, Bin, Eiriksdottir, Gudny, Yang, Xia, Orth, Anthony P, Jennings, Lori L, Gudnason, Vilmundur
Format: Journal Article
Language:English
Published: United States 24.08.2018
Subjects:
Aptamers, Nucleotide
Blood Proteins - analysis
Blood Proteins - genetics
Cardiovascular Diseases - genetics
Genetic Predisposition to Disease
Genetic Variation
Humans
Iceland
Metabolic Diseases - genetics
Metabolic Networks and Pathways
Proteome - analysis
Proteome - genetics
Proteomics - methods
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary: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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.aaq1327