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

Emilsson, Valur; Gudmundsdottir, Valborg; Gudjonsson, Alexander; Jonmundsson, Thorarinn; Jonsson, Brynjolfur G; Karim, Mohd A; Ilkov, Marjan; Staley, James R; Gudmundsson, Elias F; Launer, Lenore J; Lindeman, Jan H; Morton, Nicholas M; Aspelund, Thor; Lamb, John R; Jennings, Lori L; Gudnason, Vilmundur

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Authors

Emilsson, Valur

Gudmundsdottir, Valborg

Gudjonsson, Alexander

Jonmundsson, Thorarinn

Jonsson, Brynjolfur G

Karim, Mohd A

Ilkov, Marjan

Publication Date

2022-01-25

Journal Title

Nat Commun

ISSN

2041-1723

Publisher

Springer Science and Business Media LLC

Volume

Issue

Language

eng

Type

Article

This Version

VoR

Metadata

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Citation

Emilsson, V., Gudmundsdottir, V., Gudjonsson, A., Jonmundsson, T., Jonsson, B. G., Karim, M. A., Ilkov, M., et al. (2022). Coding and regulatory variants are associated with serum protein levels and disease.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-28081-6

Abstract

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.

Keywords

Humans, Disease, Genetic Predisposition to Disease, Blood Proteins, Proteome, Genotype, Polymorphism, Single Nucleotide, Aged, Iceland, Female, Male, Exome

Sponsorship

Icelandic Centre for Research (195761-051)

NIA NIH HHS (R01 AG065596, N01AG12100)

Wellcome Trust (206194)

NIDA NIH HHS (HHSN271201200022C)

Identifiers

PMC8789809, 35079000

External DOI: https://doi.org/10.1038/s41467-022-28081-6

This record's URL: https://www.repository.cam.ac.uk/handle/1810/334479

Rights

Attribution 4.0 International

Licence URL: https://creativecommons.org/licenses/by/4.0/

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