Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, Jiangsu, P.R. China.
Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.
Scand J Rheumatol. 2023 Jul;52(4):335-341. doi: 10.1080/03009742.2022.2070988. Epub 2022 Jun 6.
Rheumatoid arthritis (RA) is suggested to be implicated in the development of cardiometabolic diseases. We conducted a Mendelian randomization (MR) study to assess potential causality for associations of RA with the risk of cardiometabolic diseases, including type 2 diabetes (T2D), coronary artery disease (CAD), and ischaemic stroke.
Seventy independent single-nucleotide polymorphisms (SNPs) associated with RA were identified as instrumental variables from a genome-wide association study (GWAS) of 58 284 European subjects. Summary-level data for the associations of the 70 genetic variants with T2D, CAD, and ischaemic stroke were taken from three GWASs with a total of 1 529 131 participants. Inverse-variance weighted (IVW) MR was used in the main analyses.
The main IVW MR analysis showed that genetically determined RA was associated with higher risks of T2D [odds ratio (OR): 1.04, 95% confidence interval (CI) 1.02-1.05; p < 0.001] and CAD (OR: 1.02, 95% CI 1.00-1.03; p = 0.012), but not ischaemic stroke (OR: 1.00, 95% CI 0.99-1.02; p = 0.961). Sensitivity analyses with multiple MR methods confirmed these associations. MR-Egger regression showed no evidence of pleiotropy in the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke. Leave-one-out sensitivity analysis showed that the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke was not driven by any individual SNP.
Genetically determined RA was associated with increased risks of T2D and CAD, suggesting that RA plays a crucial role in the pathogenesis of T2D and CAD.
类风湿关节炎（RA）被认为与心血管代谢疾病的发生有关。我们进行了一项孟德尔随机化（MR）研究，以评估 RA 与心血管代谢疾病（包括 2 型糖尿病（T2D）、冠心病（CAD）和缺血性中风）风险之间的关联的因果关系。
从 58284 名欧洲受试者的全基因组关联研究（GWAS）中确定了 70 个与 RA 相关的独立单核苷酸多态性（SNP）作为工具变量。从三个 GWAS 中获取了与 70 个遗传变异与 T2D、CAD 和缺血性中风的关联的汇总水平数据，这三个 GWAS 共有 1529131 名参与者。主要分析采用逆方差加权（IVW）MR。
主要的 IVW MR 分析表明，遗传确定的 RA 与 T2D 的更高风险相关[比值比（OR）：1.04，95%置信区间（CI）1.02-1.05；p<0.001]和 CAD（OR：1.02，95%CI 1.00-1.03；p=0.012），但与缺血性中风无关（OR：1.00，95%CI 0.99-1.02；p=0.961）。使用多种 MR 方法的敏感性分析证实了这些关联。MR-Egger 回归表明，遗传确定的 RA 与 T2D、CAD 和缺血性中风风险之间的关联没有表现出偏倚的证据。逐一缺失敏感性分析表明，遗传确定的 RA 与 T2D、CAD 和缺血性中风风险之间的关联不是由任何单个 SNP 驱动的。
遗传确定的 RA 与 T2D 和 CAD 的风险增加相关，表明 RA 在 T2D 和 CAD 的发病机制中起着关键作用。
