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

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 g...

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Veröffentlicht in:Nature communications Jg. 13; H. 1; S. 480 - 13
Hauptverfasser: Gudjonsson, Alexander, Gudmundsdottir, Valborg, Axelsson, Gisli T., Gudmundsson, Elias F., Jonsson, Brynjolfur G., Launer, Lenore J., Lamb, John R., Jennings, Lori L., Aspelund, Thor, Emilsson, Valur, Gudnason, Vilmundur
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 25.01.2022
Nature Publishing Group
Nature Portfolio
Schlagworte:
45/43
631/208/212
631/208/480
631/45/475
82/79
Aged
Aged, 80 and over
Blood Proteins - genetics
Cohort Studies
Disease
Disease - classification
Disease - genetics
Female
Genetic control
Genetic diversity
Genetic effects
Genetic Predisposition to Disease
Genetic variance
Genetics
Genome, Human
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Genotypes
Humanities and Social Sciences
Humans
Iceland
Intolerance
Loci
Male
multidisciplinary
Mutation
Phenotypes
Phenotyping
Pleiotropy
Polymorphism, Single Nucleotide
Proteins
Quantitative Trait Loci
Science
Science (multidisciplinary)
Serum proteins
Iceland
ISSN:2041-1723, 2041-1723
Online-Zugang:Volltext
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Zusammenfassung: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. Circulating proteins have been linked to many conditions, and understanding their genetic control can lead to understanding of disease. Here, the authors associate common genetic variants with protein levels, finding overlap of genetic associations with circulating proteins and complex disease.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-27850-z