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

Gudjonsson, Alexander, Gudmundsdottir, Valborg, Gudmundsson, Elias F, Jonsson, Brynjolfur G, Launer, Lenore J, Lamb, John R, Jennings, Lori, Aspelund, Thor, Emilsson, Valur and Gudnason, Vilmundur (2022) A genome-wide association study of serum proteins reveals shared loci with common diseases. Nature communications.


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.

Item Type: Article
Keywords: proteomics, SomaScan, disease phenotypes, genetic associations
Date Deposited: 08 Feb 2022 00:45
Last Modified: 08 Feb 2022 00:45


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