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

Valur Emilsson; Marjan Ilkov; John R. Lamb; Nancy Finkel; Elias F. Gudmundsson; Rebecca Pitts; Heather Hoover; Valborg Gudmundsdottir; Shane R. Horman; Thor Aspelund; Le Shu; Vladimir Trifonov; Sigurdur Sigurdsson; Andrei Manolescu; Jun Zhu; Örn Olafsson; Johanna Jakobsdottir; Scott A. Lesley; Jeremy To; Jia Zhang; Tamara B. Harris; Lenore J. Launer; Bin Zhang; Gudny Eiriksdottir; Xia Yang; Anthony P. Orth; Lori L. Jennings; Vilmundur Gudnason

doi:10.1126/science.aaq1327

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

Valur Emilsson
, Marjan Ilkov
, John R. Lamb
, Nancy Finkel
, Elias F. Gudmundsson
, Rebecca Pitts
, Heather Hoover
, Valborg Gudmundsdottir
, Shane R. Horman
, Thor Aspelund
, Le Shu
, Vladimir Trifonov
, Sigurdur Sigurdsson
, Andrei Manolescu
, Jun Zhu
, Örn Olafsson
, Johanna Jakobsdottir
, Scott A. Lesley
, Jeremy To
, Jia Zhang

Tamara B. Harris, Lenore J. Launer, Bin Zhang, Gudny Eiriksdottir, Xia Yang, Anthony P. Orth, Lori L. Jennings, Vilmundur Gudnason

University of Iceland, Reykjavik University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	aaq1327
Journal	Science
Volume	361
Issue number	6404
DOIs	https://doi.org/10.1126/science.aaq1327
Publication status	Published - 24 Aug 2018

Bibliographical note

Funding Information: upported by Novartis Institute for Biomedical Research (NIBR), HA, and in part by the intramural research program at the National nstitute of Aging (N01-AG-12100 and HHSN271201200022C), the Althingi (the Icelandic Parliament), and the Icelandic Centre for esearch (RANNIS) grant 141101-051. We thank the staff at SomaLogic (CO) for performing the assays to measure protein levels, and P. MacNamara and G. Joyce of the Genomics Institute of the Novartis Research Foundation (GNF) for their leadership in supporting this work. We thank J. Loureiro, V. Swaroop, S. Abubucker, and F. Mapa of NIBR Cambridge for their contributions in support of the mass spectrometry workflow. We thank K. Bjarnadóttir, S. Gunnarsdóttir, and A. Hauksdóttir at the Icelandic Heart Association (IHA) for all specimen handling. Publisher Copyright: 2017 © The Authors

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10.1126/science.aaq1327

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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., ... Gudnason, V. (2018). Co-regulatory networks of human serum proteins link genetics to disease. Science, 361(6404), Article aaq1327. https://doi.org/10.1126/science.aaq1327

@article{e5d953b0e79d47cba8edd2e03ba7d8e1,

title = "Co-regulatory networks of human serum proteins link genetics to disease",

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.",

author = "Valur Emilsson and Marjan Ilkov and Lamb, \{John R.\} and Nancy Finkel and Gudmundsson, \{Elias F.\} and Rebecca Pitts and Heather Hoover and Valborg Gudmundsdottir and Horman, \{Shane R.\} and Thor Aspelund and Le Shu and Vladimir Trifonov and Sigurdur Sigurdsson and Andrei Manolescu and Jun Zhu and {\"O}rn Olafsson and Johanna Jakobsdottir and Lesley, \{Scott A.\} and Jeremy To and Jia Zhang and Harris, \{Tamara B.\} and Launer, \{Lenore J.\} and Bin Zhang and Gudny Eiriksdottir and Xia Yang and Orth, \{Anthony P.\} and Jennings, \{Lori L.\} and Vilmundur Gudnason",

note = "Funding Information: upported by Novartis Institute for Biomedical Research (NIBR), HA, and in part by the intramural research program at the National nstitute of Aging (N01-AG-12100 and HHSN271201200022C), the Althingi (the Icelandic Parliament), and the Icelandic Centre for esearch (RANNIS) grant 141101-051. We thank the staff at SomaLogic (CO) for performing the assays to measure protein levels, and P. MacNamara and G. Joyce of the Genomics Institute of the Novartis Research Foundation (GNF) for their leadership in supporting this work. We thank J. Loureiro, V. Swaroop, S. Abubucker, and F. Mapa of NIBR Cambridge for their contributions in support of the mass spectrometry workflow. We thank K. Bjarnad{\'o}ttir, S. Gunnarsd{\'o}ttir, and A. Hauksd{\'o}ttir at the Icelandic Heart Association (IHA) for all specimen handling. Publisher Copyright: 2017 {\textcopyright} The Authors",

year = "2018",

month = aug,

day = "24",

doi = "10.1126/science.aaq1327",

language = "English",

volume = "361",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6404",

}

Emilsson, V, Ilkov, M, Lamb, JR, Finkel, N, Gudmundsson, EF, Pitts, R, Hoover, H, Gudmundsdottir, V, Horman, SR, Aspelund, T, Shu, L, Trifonov, V, Sigurdsson, S, Manolescu, A, Zhu, J, Olafsson, Ö , Jakobsdottir, J, Lesley, SA, To, J, Zhang, J, Harris, TB, Launer, LJ, Zhang, B, Eiriksdottir, G, Yang, X, Orth, AP, Jennings, LL & Gudnason, V 2018, 'Co-regulatory networks of human serum proteins link genetics to disease', Science, vol. 361, no. 6404, aaq1327. https://doi.org/10.1126/science.aaq1327

TY - JOUR

T1 - Co-regulatory networks of human serum proteins link genetics to disease

AU - Emilsson, Valur

AU - Ilkov, Marjan

AU - Lamb, John R.

AU - Finkel, Nancy

AU - Gudmundsson, Elias F.

AU - Pitts, Rebecca

AU - Hoover, Heather

AU - Gudmundsdottir, Valborg

AU - Horman, Shane R.

AU - Aspelund, Thor

AU - Shu, Le

AU - Trifonov, Vladimir

AU - Sigurdsson, Sigurdur

AU - Manolescu, Andrei

AU - Zhu, Jun

AU - Olafsson, Örn

AU - Jakobsdottir, Johanna

AU - Lesley, Scott A.

AU - To, Jeremy

AU - Zhang, Jia

AU - Harris, Tamara B.

AU - Launer, Lenore J.

AU - Zhang, Bin

AU - Eiriksdottir, Gudny

AU - Yang, Xia

AU - Orth, Anthony P.

AU - Jennings, Lori L.

AU - Gudnason, Vilmundur

N1 - Funding Information: upported by Novartis Institute for Biomedical Research (NIBR), HA, and in part by the intramural research program at the National nstitute of Aging (N01-AG-12100 and HHSN271201200022C), the Althingi (the Icelandic Parliament), and the Icelandic Centre for esearch (RANNIS) grant 141101-051. We thank the staff at SomaLogic (CO) for performing the assays to measure protein levels, and P. MacNamara and G. Joyce of the Genomics Institute of the Novartis Research Foundation (GNF) for their leadership in supporting this work. We thank J. Loureiro, V. Swaroop, S. Abubucker, and F. Mapa of NIBR Cambridge for their contributions in support of the mass spectrometry workflow. We thank K. Bjarnadóttir, S. Gunnarsdóttir, and A. Hauksdóttir at the Icelandic Heart Association (IHA) for all specimen handling. Publisher Copyright: 2017 © The Authors

PY - 2018/8/24

Y1 - 2018/8/24

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85052129897

U2 - 10.1126/science.aaq1327

DO - 10.1126/science.aaq1327

M3 - Article

C2 - 30072576

SN - 0036-8075

VL - 361

JO - Science

JF - Science

IS - 6404

M1 - aaq1327

ER -

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

Abstract

Bibliographical note

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