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

Opin vísindi
→
IRIS
→
IRIS
→
Skoða verk

dc.contributor.author	orcid.org/0000-0001-9982-0524 Emilsson, Valur
dc.contributor.author	Gudmundsdottir, Valborg
dc.contributor.author	Gudjonsson, Alexander
dc.contributor.author	Jonmundsson, Thorarinn
dc.contributor.author	Jonsson, Brynjolfur G
dc.contributor.author	Karim, Mohd A
dc.contributor.author	Ilkov, Marjan
dc.contributor.author	Staley, James R
dc.contributor.author	Gudmundsson, Elias F
dc.contributor.author	Launer, Lenore J
dc.contributor.author	Lindeman, Jan H
dc.contributor.author	Morton, Nicholas M
dc.contributor.author	orcid.org/0000-0002-7998-5433 Aspelund, Thor
dc.contributor.author	Lamb, John R
dc.contributor.author	Jennings, Lori L
dc.contributor.author	orcid.org/0000-0001-5696-0084 Gudnason, Vilmundur
dc.date.accessioned	2022-08-24T01:03:23Z
dc.date.available	2022-08-24T01:03:23Z
dc.date.issued	2022-01-25
dc.identifier.citation	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
dc.identifier.issn	2041-1723
dc.identifier.other	51805048
dc.identifier.other	2d34bf85-9a01-4094-8477-9e7dfee36eb1
dc.identifier.other	35079000
dc.identifier.other	PubMedCentral: PMC8789809
dc.identifier.other	85123475539
dc.identifier.other	unpaywall: 10.1038/s41467-022-28081-6
dc.identifier.other	000747410400014
dc.identifier.uri	https://hdl.handle.net/20.500.11815/3343
dc.description	© 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).
dc.description.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.
dc.format.extent	6974860
dc.format.extent	481
dc.language.iso	en
dc.relation.ispartofseries	Nature Communications; 13(1)
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Aged
dc.subject	Blood Proteins/genetics
dc.subject	Disease/classification
dc.subject	Exome/genetics
dc.subject	Female
dc.subject	Genetic Predisposition to Disease
dc.subject	Genotype
dc.subject	Humans
dc.subject	Iceland
dc.subject	Male
dc.subject	Polymorphism, Single Nucleotide
dc.subject	Proteome/metabolism
dc.subject	Blóðprótín
dc.subject	Multidisciplinary
dc.subject	General Physics and Astronomy
dc.subject	General Chemistry
dc.subject	General Biochemistry,Genetics and Molecular Biology
dc.title	Coding and regulatory variants are associated with serum protein levels and disease
dc.type	/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version	Peer reviewed
dc.identifier.doi	10.1038/s41467-022-28081-6
dc.relation.url	http://www.scopus.com/inward/record.url?scp=85123475539&partnerID=8YFLogxK
dc.contributor.department	Faculty of Medicine
dc.contributor.school	Health Sciences