| Title: | Genetic analysis of over half a million people characterises C-reactive protein loci |
| Journal: | Nature Communications |
| Published: | 22 Apr 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35459240/ |
| DOI: | https://doi.org/10.1038/s41467-022-29650-5 |
| URL: | https://www.nature.com/articles/s41467-022-29650-5.pdf |
| Citations: | 71 (65 in last 2 years) as of 8 Aug 2024 |
Publication 12400
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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.</p>
9 Keywords
- C-Reactive Protein
- Genetic Loci
- Genome-Wide Association Study
- Humans
- Inflammation
- Male
- Mendelian Randomization Analysis
- Phenomics
- Polymorphism, Single Nucleotide
17 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 13436 | Genetic determinants and biological pathways linking major inflammatory biomarkers to disease outcomes |
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