Said, S., Pazoki, R., Karhunen, V. et al. Genetic analysis of over half a million people characterises C-reactive protein loci. Nat Commun 13, 2198 (2022). https://doi.org/10.1038/s41467-022-29650-5
Genetic analysis of over half a million people characterises C-reactive protein loci
|Author:||Said, Saredo1; Pazoki, Raha1,2,3,4; Karhunen, Ville1,5,6;|
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
2Cardiovascular and Metabolic Research Group, Department of Life Sciences, Brunel University London, London, UK
3The Centre for Inflammation Research and Translational Medicine (CIRTM), Brunel University London, London, UK
4Centre for Health and Well-being Across the Life Course, Brunel University London, London, UK
5Centre for Life Course Health Research, University of Oulu, Oulu, Finland
6Research Unit of Mathematical Sciences, University of Oulu, Oulu, Finland
7Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
8Department of Intensive Care, University Hospital Antwerp, Antwerp, Belgium
9Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
10Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK
11Department of Epidemiology, University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands
12Division of Preventive Medicine, Brigham & Women’s Hospital, Boston, MA, 02115, USA
13Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
14MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG, UK
15UK Dementia Research Institute at Imperial College London, Burlington Danes Building, Hammersmith Hospital, DuCane Road, London, W12 0NN, UK
16National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, W2 1PG, UK
|Online Access:||PDF Full Text (PDF, 1.6 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022102563241
|Publish Date:|| 2022-10-25
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
We thank all cohorts and all participants for making this research possible. The authors thank the UK Biobank for providing the data to conduct this study under application ID 13436. We thank Inflammation working group of CHARGE Consortium for allowing the acquisition of their CRP GWAS summary data. This work was enabled by the computing resources developed by David Mosen-Ansorena and Gao He, and support from the Imperial College Research Computing Service. This work is supported by the UK 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). The funding organisations had no role in design and conduct of the study, including data collection through to interpretation and paper preparation, review, or approval.
The online version contains supplementary material available at https://doi.org/10.1038/s41467-022-29650-5.
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