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

Saredo Said; Raha Pazoki; Ville Karhunen; Urmo Võsa; Symen Ligthart; Barbara Bodinier; Fotios Koskeridis; Paul Welsh; Behrooz Z Alizadeh; Daniel I Chasman; Naveed Sattar; Marc Chadeau-Hyam; Evangelos Evangelou; Marjo-Riitta Jarvelin; Paul Elliott; Ioanna Tzoulaki; Abbas Dehghan

doi:10.1038/s41467-022-29650-5

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

Nat Commun. 2022 Apr 22;13(1):2198. doi: 10.1038/s41467-022-29650-5.

Authors

Saredo Said¹, Raha Pazoki^{1

2

3

4}, Ville Karhunen^{1

5

6}, Urmo Võsa⁷, Symen Ligthart⁸, Barbara Bodinier¹, Fotios Koskeridis⁹, Paul Welsh¹⁰, Behrooz Z Alizadeh¹¹, Daniel I Chasman^{12

13}, Naveed Sattar¹⁰, Marc Chadeau-Hyam^{1

14}, Evangelos Evangelou^{1

9}, Marjo-Riitta Jarvelin^{1

5}, Paul Elliott^{1

14

15

16}, Ioanna Tzoulaki^#^{1

9

14

15}, Abbas Dehghan^#^{17

18

19}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
² Cardiovascular and Metabolic Research Group, Department of Life Sciences, Brunel University London, London, UK.
³ The Centre for Inflammation Research and Translational Medicine (CIRTM), Brunel University London, London, UK.
⁴ Centre for Health and Well-being Across the Life Course, Brunel University London, London, UK.
⁵ Centre for Life Course Health Research, University of Oulu, Oulu, Finland.
⁶ Research Unit of Mathematical Sciences, University of Oulu, Oulu, Finland.
⁷ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
⁸ Department of Intensive Care, University Hospital Antwerp, Antwerp, Belgium.
⁹ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
¹⁰ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
¹¹ Department of Epidemiology, University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands.
¹² Division of Preventive Medicine, Brigham & Women's Hospital, Boston, MA, 02115, USA.
¹³ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁴ MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG, UK.
¹⁵ UK Dementia Research Institute at Imperial College London, Burlington Danes Building, Hammersmith Hospital, DuCane Road, London, W12 0NN, UK.
¹⁶ National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, W2 1PG, UK.
¹⁷ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. a.dehghan@imperial.ac.uk.
¹⁸ MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, W2 1PG, UK. a.dehghan@imperial.ac.uk.
¹⁹ UK Dementia Research Institute at Imperial College London, Burlington Danes Building, Hammersmith Hospital, DuCane Road, London, W12 0NN, UK. a.dehghan@imperial.ac.uk.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

C-Reactive Protein* / genetics
C-Reactive Protein* / metabolism
Genetic Loci
Genome-Wide Association Study*
Humans
Inflammation / genetics
Male
Mendelian Randomization Analysis
Phenomics
Polymorphism, Single Nucleotide

Substances

C-Reactive Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding