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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/24511
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dc.contributor.authorSaid, S-
dc.contributor.authorPazoki, R-
dc.contributor.authorKarhunen, V-
dc.contributor.authorVõsa, U-
dc.contributor.authorLigthart, S-
dc.contributor.authorBodinier, B-
dc.contributor.authorKoskeridis, F-
dc.contributor.authorWelsh, P-
dc.contributor.authorAlizadeh, BZ-
dc.contributor.authorChasman, DI-
dc.contributor.authorSattar, N-
dc.contributor.authorChadeau-Hyam, M-
dc.contributor.authorEvangelou, E-
dc.contributor.authorJarvelin, M-R-
dc.contributor.authorElliott, P-
dc.contributor.authorTzoulaki, I-
dc.contributor.authorDehghan, A-
dc.date.accessioned2022-04-28T11:59:51Z-
dc.date.available2022-12-
dc.date.available2022-04-28T11:59:51Z-
dc.date.issued2022-04-22-
dc.identifier2198-
dc.identifier.citationSaid, 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.en_US
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/24511-
dc.descriptionData 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/).en_US
dc.description.abstractCopyright © 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.en_US
dc.description.sponsorshipUK Dementia Research Institute at Imperial College, which receives its funding from UK DRI Ltd. (funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK) and the British Heart Foundation Centre for Research Excellence at Imperial College London and the National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London. S.S. received funding from the Medical Research Council – Public Health England (MRC-PHE) Centre for Environment and Health awarded studentship, of which funding is derived from the MRC Industrial Strategy Fund. I.T and F.K. have received funding from the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under grant agreement No 1312. R.P. holds a fellowship supported by Rutherford Fund from Medical Research Council (MR/R0265051/1 and MR/R0265051/2). V.K. is funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant (721567).en_US
dc.format.extent1 - 10-
dc.format.mediumElectronic-
dc.languageEnglish-
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.rightsCopyright © The Author(s) 2022. Rights and permissions: Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.-
dc.titleGenetic analysis of over half a million people characterises C-reactive protein locien_US
dc.typeJournal articleen_US
dc.identifier.doihttps://doi.org/10.1038/s41467-022-29650-5-
dc.relation.isPartOfNature Communications-
pubs.issue1-
pubs.publication-statusPublished online-
pubs.volume13-
dc.identifier.eissn2041-1723-
Appears in Collections:Dept of Life Sciences Research Papers

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