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
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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.
AbstractList	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.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. 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.
Author	Emilsson, Valur Pitts, Rebecca To, Jeremy Orth, Anthony P Ilkov, Marjan Gudnason, Vilmundur Shu, Le Lamb, John R Harris, Tamara B Manolescu, Andrei Sigurdsson, Sigurdur Finkel, Nancy Jakobsdottir, Johanna Jennings, Lori L Aspelund, Thor Gudmundsdottir, Valborg Eiriksdottir, Gudny Hoover, Heather Olafsson, Örn Trifonov, Vladimir Gudmundsson, Elias F Launer, Lenore J Horman, Shane R Yang, Xia Lesley, Scott A Zhang, Bin Zhu, Jun Zhang, Jia
Author_xml	– sequence: 1 givenname: Valur orcidid: 0000-0001-9982-0524 surname: Emilsson fullname: Emilsson, Valur email: valur@hjarta.is, v.gudnason@hjarta.is, jlamb@gnf.org organization: Faculty of Pharmacology, University of Iceland, 101 Reykjavik, Iceland – sequence: 2 givenname: Marjan orcidid: 0000-0002-1464-9252 surname: Ilkov fullname: Ilkov, Marjan organization: Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland – sequence: 3 givenname: John R surname: Lamb fullname: Lamb, John R email: valur@hjarta.is, v.gudnason@hjarta.is, jlamb@gnf.org organization: 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 – sequence: 4 givenname: Nancy orcidid: 0000-0002-8937-4150 surname: Finkel fullname: Finkel, Nancy organization: Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA 02139, USA – sequence: 5 givenname: Elias F orcidid: 0000-0002-7661-4872 surname: Gudmundsson fullname: Gudmundsson, Elias F organization: Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland – sequence: 6 givenname: Rebecca orcidid: 0000-0003-4733-414X surname: Pitts fullname: Pitts, Rebecca organization: Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA 02139, USA – sequence: 7 givenname: Heather orcidid: 0000-0002-2337-0288 surname: Hoover fullname: Hoover, Heather organization: Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA 02139, USA – sequence: 8 givenname: Valborg orcidid: 0000-0002-7459-1603 surname: Gudmundsdottir fullname: Gudmundsdottir, Valborg organization: Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland – sequence: 9 givenname: Shane R orcidid: 0000-0003-2513-5721 surname: Horman fullname: Horman, Shane R organization: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA – sequence: 10 givenname: Thor orcidid: 0000-0002-7998-5433 surname: Aspelund fullname: Aspelund, Thor organization: Centre of Public Health Sciences, University of Iceland, 101 Reykjavik, Iceland – sequence: 11 givenname: Le orcidid: 0000-0001-5428-1969 surname: Shu fullname: Shu, Le organization: Department of Integrative Biology and Physiology, University of California, Los Angeles CA, USA – sequence: 12 givenname: Vladimir orcidid: 0000-0001-8374-6024 surname: Trifonov fullname: Trifonov, Vladimir organization: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA – sequence: 13 givenname: Sigurdur surname: Sigurdsson fullname: Sigurdsson, Sigurdur organization: Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland – sequence: 14 givenname: Andrei orcidid: 0000-0002-0713-4664 surname: Manolescu fullname: Manolescu, Andrei organization: School of Science and Engineering, Mentavegur 1, IS-101, Reykjavik University, 101 Reykjavik, Iceland – sequence: 15 givenname: Jun surname: Zhu fullname: Zhu, Jun organization: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA – sequence: 16 givenname: Örn surname: Olafsson fullname: Olafsson, Örn organization: Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland – sequence: 17 givenname: Johanna surname: Jakobsdottir fullname: Jakobsdottir, Johanna organization: Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland – sequence: 18 givenname: Scott A orcidid: 0000-0002-7905-8840 surname: Lesley fullname: Lesley, Scott A organization: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA – sequence: 19 givenname: Jeremy orcidid: 0000-0002-8743-632X surname: To fullname: To, Jeremy organization: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA – sequence: 20 givenname: Jia orcidid: 0000-0001-6292-846X surname: Zhang fullname: Zhang, Jia organization: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA – sequence: 21 givenname: Tamara B orcidid: 0000-0002-0855-8477 surname: Harris fullname: Harris, Tamara B organization: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892-9205, USA – sequence: 22 givenname: Lenore J surname: Launer fullname: Launer, Lenore J organization: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892-9205, USA – sequence: 23 givenname: Bin surname: Zhang fullname: Zhang, Bin organization: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA – sequence: 24 givenname: Gudny surname: Eiriksdottir fullname: Eiriksdottir, Gudny organization: Icelandic Heart Association, Holtasmari 1, IS-201 Kopavogur, Iceland – sequence: 25 givenname: Xia orcidid: 0000-0002-3971-038X surname: Yang fullname: Yang, Xia organization: Department of Integrative Biology and Physiology, University of California, Los Angeles CA, USA – sequence: 26 givenname: Anthony P surname: Orth fullname: Orth, Anthony P organization: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA – sequence: 27 givenname: Lori L orcidid: 0000-0001-5130-8417 surname: Jennings fullname: Jennings, Lori L organization: Novartis Institutes for Biomedical Research, 22 Windsor Street, Cambridge, MA 02139, USA – sequence: 28 givenname: Vilmundur surname: Gudnason fullname: Gudnason, Vilmundur email: valur@hjarta.is, v.gudnason@hjarta.is, jlamb@gnf.org organization: Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/30072576$$D View this record in MEDLINE/PubMed
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References	31171530 - Clin Chem. 2019 Oct;65(10):1204-1206. doi: 10.1373/clinchem.2018.299065.
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Snippet	Proteins circulating in the blood are critical for age-related disease processes; however, the serum proteome has remained largely unexplored. To this end,...
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SubjectTerms	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
Title	Co-regulatory networks of human serum proteins link genetics to disease
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