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

Saredo Said, Raha Pazoki, Ville Karhunen, Urmo Võsa, Symen Ligthart, Barbara Bodinier, Fotios Koskeridis, Paul Welsh, Behrooz Z. Alizadeh, Daniel I. Chasman, Naveed Sattar, Marc Chadeau-Hyam, Evangelos Evangelou, Marjo-Riitta Jarvelin, Paul Elliott, Ioanna Tzoulaki and Abbas Dehghan ()
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Saredo Said: Imperial College London
Raha Pazoki: Imperial College London
Ville Karhunen: Imperial College London
Urmo Võsa: Institute of Genomics, University of Tartu
Symen Ligthart: University Hospital Antwerp
Barbara Bodinier: Imperial College London
Fotios Koskeridis: University of Ioannina Medical School
Paul Welsh: University of Glasgow
Behrooz Z. Alizadeh: University of Groningen and University Medical Centre Groningen
Daniel I. Chasman: Brigham & Women’s Hospital
Naveed Sattar: University of Glasgow
Marc Chadeau-Hyam: Imperial College London
Evangelos Evangelou: Imperial College London
Marjo-Riitta Jarvelin: Imperial College London
Paul Elliott: Imperial College London
Ioanna Tzoulaki: Imperial College London
Abbas Dehghan: Imperial College London

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-29650-5

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