Genetic analysis of over half a million people characterises C-reactive protein loci

Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Resea...

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Bibliographic Details
Published in:Nature communications Vol. 13; no. 1; pp. 2198 - 10
Main Authors: Said, Saredo, Pazoki, Raha, Karhunen, Ville, Võsa, Urmo, Ligthart, Symen, Bodinier, Barbara, Koskeridis, Fotios, Welsh, Paul, Alizadeh, Behrooz Z., Chasman, Daniel I., Sattar, Naveed, Chadeau-Hyam, Marc, Evangelou, Evangelos, Jarvelin, Marjo-Riitta, Elliott, Paul, Tzoulaki, Ioanna, Dehghan, Abbas
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 22.04.2022
Nature Publishing Group
Nature Portfolio
Subjects:
45/43
631/114/1314
631/208/205/2138
631/250/256/2515
Aging
Airway management
Biomarkers
C-reactive protein
C-Reactive Protein - genetics
C-Reactive Protein - metabolism
Chronic illnesses
Clinical outcomes
Epidemiology
Gene expression
Gene loci
Genetic analysis
Genetic Loci
Genome-wide association studies
Genome-Wide Association Study
Humanities and Social Sciences
Humans
Inflammation
Inflammation - genetics
Male
Mendelian Randomization Analysis
Mental disorders
multidisciplinary
Phenomics
Polymorphism, Single Nucleotide
Prostate cancer
Proteins
Schizophrenia
Science
Science (multidisciplinary)
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels ( p  ≤ 3.2 ×10 −6 ) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases. Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of inflammation, in >500,000 Europeans, along with associated pathways, clinical outcomes and potential causal associations with disease.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-29650-5