Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Cardiovascular and Metabolic Research Group, Department of Life Sciences, Brunel University London, London, UK.
Nat Commun. 2022 Apr 22;13(1):2198. doi: 10.1038/s41467-022-29650-5.
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) 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.
慢性低度炎症与多种慢性疾病有关。我们报告了在英国生物银行参与者（N=427367，欧洲血统）和基因组流行病学中的心脏和衰老研究队列（CHARGE）联盟（总计 N=575531，欧洲血统）中对 C 反应蛋白（CRP）的最大全基因组关联研究（GWAS），CRP 是全身性炎症的标志物。我们确定了 266 个独立的基因座，其中 211 个以前没有报道过。基因集分析突出了 42 个与 CRP 水平相关的基因集（p≤3.2×10），组织表达分析表明 CRP 相关基因与肝脏和全血基因表达密切相关。表型全基因组关联研究确定了与遗传决定的 CRP 相关的 27 种临床结果，随后的孟德尔随机化分析支持 CRP 与精神分裂症、慢性气道阻塞和前列腺癌之间存在因果关系。我们的研究结果确定了慢性低度炎症的遗传位点和功能特性，并为与一系列疾病的因果关系提供了证据。
