ABS1212-HPR GENETIC EVIDENCE FOR THE CAUSAL ROLE OF C-REACTIVE PROTEIN IN THE SUSCEPTIBILITY TO AUTOIMMUNE DISEASES: A COMPREHENSIVE MENDELIAN RANDOMIZATION STUDY

作者：Wanying Xie, Jirong Yue, Xiaojuan Ma, R. Zhao, X. Hao, Mingyang Chang, John Wang · 发表于：Annals of the Rheumatic Diseases · 年份：2025 · DOI：10.1016/j.ard.2025.06.984 · 研究领域：Diabetes and associated disorders

Background: Patients with autoimmune diseases (ADs) often exhibit systemic low-grade inflammation, commonly reflected in elevated C-reactive protein (CRP) levels. CRP, a plasma protein produced by the liver, is a crucial component of the innate immune system, playing a key role in recognizing pathogens and altered self-determinants [1]. Observational studies have consistently shown a significant association between CRP levels and the risk of Ads [2, 3]. However, the causal nature of this association remains unclear. While observational studies provide valuable insights, they are often subject to selection bias, residual confounding, and reverse causality, which complicate the interpretation of these associations. To address these limitations, Mendelian randomization (MR) has emerged as a promising approach. By leveraging genetic variants as instrumental variables, MR helps reduce confounding and reverse causality, providing stronger evidence for causal relationships between CRP levels and Ads [4]. Objectives: This study aimed to infer the causality between CRP and the risk of six ADs by means of the MR analysis. Methods: This study investigated the bidirectional effects between CRP and six major ADs: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), Crohn's disease (CD), ulcerative colitis (UC), and primary sclerosing cholangitis (PSC). To achieve this, we utilized extensive GWAS summary data from individuals of European ancestry. The linka...