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Coding and regulatory variants are associated with serum protein levels and disease

Coding and regulatory variants are associated with serum protein levels and disease

Title: Coding and regulatory variants are associated with serum protein levels and disease
Author: Emilsson, Valur   orcid.org/0000-0001-9982-0524
Gudmundsdottir, Valborg
Gudjonsson, Alexander
Jonmundsson, Thorarinn
Jonsson, Brynjolfur G
Karim, Mohd A
Ilkov, Marjan
Staley, James R
Gudmundsson, Elias F
Launer, Lenore J
... 6 more authors Show all authors
Date: 2022-01-25
Language: English
Scope: 481
School: Health Sciences
Department: Faculty of Medicine
Series: Nature Communications; 13(1)
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-022-28081-6
Subject: Aged; Blood Proteins/genetics; Disease/classification; Exome/genetics; Female; Genetic Predisposition to Disease; Genotype; Humans; Iceland; Male; Polymorphism, Single Nucleotide; Proteome/metabolism; Blóðprótín; Multidisciplinary; Physics and Astronomy (all); Chemistry (all); Biochemistry, Genetics and Molecular Biology (all)
URI: https://hdl.handle.net/20.500.11815/3343

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Emilsson , V , Gudmundsdottir , V , Gudjonsson , A , Jonmundsson , T , Jonsson , B G , Karim , M A , Ilkov , M , Staley , J R , Gudmundsson , E F , Launer , L J , Lindeman , J H , Morton , N M , Aspelund , T , Lamb , J R , Jennings , L L & Gudnason , V 2022 , ' Coding and regulatory variants are associated with serum protein levels and disease ' , Nature Communications , vol. 13 , no. 1 , 481 , pp. 481 . https://doi.org/10.1038/s41467-022-28081-6


Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins' emerging role as biomarkers and potential causative agents of a wide range of diseases.


© 2022. The Author(s). Funding Information: The study was supported by the Novartis Institute for Biomedical Research, and protein measurements for the AGES-RS cohort were performed at SomaLogic. J.R.L. and L.L.J. are employees and stockholders of Novartis. The remaining authors declare no competing interests. Funding Information: The authors acknowledge the contribution of the Icelandic Heart Association (IHA) staff to AGES-RS, as well as the involvement of all study participants. The National Institute on Aging (NIA) contracts N01-AG-12100 and HHSN271201200022C for V.G. financed the study. V.G. received funding from the NIA (1R01AG065596), and IHA received a grant from Althingi (the Icelandic Parliament). The Icelandic Research Fund (IRF) funded V.E. and Va.G. with grants 195761-051, 184845-053, and 206692-051, while Va.G. received a postdoctoral research grant from the University of Iceland Research Fund. M.A.K. was funded by Open Targets and by the Wellcome Trust Grant 206194. Publisher Copyright: © 2022, The Author(s).

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