Journal Article

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

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

2022

Overview

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. Inflammation is associated with a variety of diseases. Here, the authors identify 266 genetic loci associated with C-reactive protein levels, a marker of inflammation, in >500,000 Europeans, along with associated pathways, clinical outcomes and potential causal associations with disease.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/43 / 631/114/1314 / 631/208/205/2138 / 631/250/256/2515 / Aging / Airway management / Biomarkers / C-reactive protein / C-Reactive Protein - genetics / C-Reactive Protein - metabolism / Chronic illnesses / Clinical outcomes / Epidemiology / Gene expression / Gene loci / Genetic analysis / Genetic Loci / Genome-wide association studies / Genome-Wide Association Study / Humanities and Social Sciences / Humans / Inflammation / Inflammation - genetics / Male / Mendelian Randomization Analysis / Mental disorders / multidisciplinary / Phenomics / Polymorphism, Single Nucleotide / Prostate cancer / Proteins / Schizophrenia / Science / Science (multidisciplinary)