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

Said, S. et al. (2022) Genetic analysis of over half a million people characterises C-reactive protein loci. Nature Communications, 13, 2198. (doi: 10.1038/s41467-022-29650-5) (PMID:35459240)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sattar, Professor Naveed and Welsh, Dr Paul
Authors: Said, S., Pazoki, R., Karhunen, V., Võsa, U., Ligthart, S., Bodinier, B., Koskeridis, F., Welsh, P., Alizadeh, B. Z., Chasman, D. I., Sattar, N., Chadeau-Hyam, M., Evangelou, E., Jarvelin, M.-R., Elliott, P., Tzoulaki, I., and Dehghan, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Nature Communications 13: 2198
Publisher Policy:Reproduced under a Creative Commons License

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