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


Type
Article
Change log
Authors
Gudmundsdottir, Valborg  ORCID logo  https://orcid.org/0000-0002-7459-1603
Gudjonsson, Alexander 
Jonmundsson, Thorarinn  ORCID logo  https://orcid.org/0000-0001-9158-0087
Jonsson, Brynjolfur G 
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.

Description
Keywords
Aged, Blood Proteins, Disease, Exome, Female, Genetic Predisposition to Disease, Genotype, Humans, Iceland, Male, Polymorphism, Single Nucleotide, Proteome
Journal Title
Nat Commun
Conference Name
Journal ISSN
2041-1723
2041-1723
Volume Title
13
Publisher
Springer Science and Business Media LLC
Sponsorship
Icelandic Centre for Research (195761-051)
NIA NIH HHS (R01 AG065596, N01AG12100)
Wellcome Trust (206194)
NIDA NIH HHS (HHSN271201200022C)