Pleiotropic genetic architecture and novel loci for C-reactive protein levels

C-reactive protein is involved in a plethora of pathophysiological conditions. Many genetic loci associated with C-reactive protein are annotated to lipid and glucose metabolism genes supporting common biological pathways between inflammation and metabolic traits. To identify novel pleiotropic loci,...

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Veröffentlicht in:Nature communications Jg. 13; H. 1; S. 6939 - 11
Hauptverfasser: Koskeridis, Fotios, Evangelou, Evangelos, Said, Saredo, Boyle, Joseph J., Elliott, Paul, Dehghan, Abbas, Tzoulaki, Ioanna
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 14.11.2022
Nature Publishing Group
Nature Portfolio
Schlagworte:
38
45/43
631/208/205/2138
692/308/2056
692/4017
692/699/1702/393
C-reactive protein
C-Reactive Protein - genetics
Gene loci
Genes
Genetic Loci
Genetic Pleiotropy
Genetic Predisposition to Disease
Genome-wide association studies
Genome-Wide Association Study
Genomes
Glucose metabolism
Health risks
Humanities and Social Sciences
Humans
Inflammation
Inflammation - genetics
Lipid metabolism
Lipids
Mendelian Randomization Analysis
Metabolic pathways
Metabolism
multidisciplinary
Pleiotropy
Polymorphism, Single Nucleotide
Proteins
Quality
Risk analysis
Risk factors
Science
Science (multidisciplinary)
Therapeutic targets
ISSN:2041-1723, 2041-1723
Online-Zugang:Volltext
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Zusammenfassung:C-reactive protein is involved in a plethora of pathophysiological conditions. Many genetic loci associated with C-reactive protein are annotated to lipid and glucose metabolism genes supporting common biological pathways between inflammation and metabolic traits. To identify novel pleiotropic loci, we perform multi-trait analysis of genome-wide association studies on C-reactive protein levels along with cardiometabolic traits, followed by a series of in silico analyses including colocalization, phenome-wide association studies and Mendelian randomization. We find 41 novel loci and 19 gene sets associated with C-reactive protein with various pleiotropic effects. Additionally, 41 variants colocalize between C-reactive protein and cardiometabolic risk factors and 12 of them display unexpected discordant effects between the shared traits which are translated into discordant associations with clinical outcomes in subsequent phenome-wide association studies. Our findings provide insights into shared mechanisms underlying inflammation and lipid metabolism, representing potential preventive and therapeutic targets. Chronic inflammation and lipometabolism share many causal genes and possibly pathways. Here, the authors use a multi-trait GWAS approach to study shared genetic determinants of low-grade inflammation, measured by C-reactive protein (CRP), and closely linked lipid and metabolic pathways.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-34688-6