A genome-wide association study of serum proteins reveals shared loci with common diseases

Alexander Gudjonsson, Valborg Gudmundsdottir, Gisli T. Axelsson, Elias F. Gudmundsson, Brynjolfur G. Jonsson, Lenore J. Launer, John R. Lamb, Lori L. Jennings, Thor Aspelund, Valur Emilsson and Vilmundur Gudnason ()
Additional contact information
Alexander Gudjonsson: Icelandic Heart Association
Valborg Gudmundsdottir: Icelandic Heart Association
Gisli T. Axelsson: Icelandic Heart Association
Elias F. Gudmundsson: Icelandic Heart Association
Brynjolfur G. Jonsson: Icelandic Heart Association
Lenore J. Launer: National Institute on Aging
John R. Lamb: GNF Novartis
Lori L. Jennings: Novartis Institutes for Biomedical Research
Thor Aspelund: Icelandic Heart Association
Valur Emilsson: Icelandic Heart Association
Vilmundur Gudnason: Icelandic Heart Association

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in solid tissues and biofluids integrated with genetic variants offers a path to deeper functional insights. Here we present a large-scale proteogenomic study in 5,368 individuals, revealing 4,035 independent associations between genetic variants and 2,091 serum proteins, of which 36% are previously unreported. The majority of both cis- and trans-acting genetic signals are unique for a single protein, although our results also highlight numerous highly pleiotropic genetic effects on protein levels and demonstrate that a protein’s genetic association profile reflects certain characteristics of the protein, including its location in protein networks, tissue specificity and intolerance to loss of function mutations. Integrating protein measurements with deep phenotyping of the cohort, we observe substantial enrichment of phenotype associations for serum proteins regulated by established GWAS loci, and offer new insights into the interplay between genetics, serum protein levels and complex disease.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-27850-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27850-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-27850-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().