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Title: | Genetic analysis of over half a million people characterises C-reactive protein loci |
Authors: | Said, S Pazoki, R Karhunen, V Võsa, U Ligthart, S Bodinier, B Koskeridis, F Welsh, P Alizadeh, BZ Chasman, DI Sattar, N Chadeau-Hyam, M Evangelou, E Jarvelin, M-R Elliott, P Tzoulaki, I Dehghan, A |
Issue Date: | 22-Apr-2022 |
Publisher: | Springer Nature |
Citation: | 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. (2022) 'Genetic analysis of over half a million people characterises C-reactive protein loci', Nature Communications, 2022, 13 (1), 2198, pp. 1-10. doi: 10.1038/s41467-022-29650-5. |
Abstract: | Copyright © The Author(s) 2022. 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. |
Description: | Data availability: The summary statistics of the CHARGE CRP GWAS used in this study is publicly available from the IEU open GWAS project accession code ieu-b-35 (Trait: C-Reactive protein level - IEU Open GWAS project (mrcieu.ac.uk)). The derived CRP GWAS meta-analysis summary statistics generated in this study has been deposited in the GWAS catalogue under accession code GCST00186 (https://www.ebi.ac.uk/gwas/). Human genome assembly GRCh37 (hg19) from Genome Reference Consortium https://www.sanger.ac.uk/data/genome-reference-consortium/). |
URI: | https://bura.brunel.ac.uk/handle/2438/24511 |
DOI: | https://doi.org/10.1038/s41467-022-29650-5 |
Other Identifiers: | 2198 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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