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) (PMCID:PMC9033829)
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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 |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Sattar, Professor Naveed and Welsh, Professor 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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