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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Vydáno v:	Science (American Association for the Advancement of Science) Ročník 361; číslo 6404; s. 769
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 24.08.2018
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1095-9203 1095-9203
DOI:	10.1126/science.aaq1327