Qiu Shizheng, Li Meijie, Jin Shunshan, Lu Haoyu, Hu Yang
School of Life Sciences and Technology, Harbin Institute of Technology, Harbin, China.
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Front Genet. 2021 Oct 21;12:745224. doi: 10.3389/fgene.2021.745224. eCollection 2021.
Significant genetic association exists between rheumatoid arthritis (RA) and cardiovascular disease. The associated mechanisms include common inflammatory mediators, changes in lipoprotein composition and function, immune responses, etc. However, the causality of RA and vascular/heart problems remains unknown. Herein, we performed Mendelian randomization (MR) analysis using a large-scale RA genome-wide association study (GWAS) dataset (462,933 cases and 457,732 controls) and six cardio-cerebrovascular disease GWAS datasets, including age angina (461,880 cases and 447,052 controls), hypertension (461,880 cases and 337,653 controls), age heart attack (10,693 cases and 451,187 controls), abnormalities of heartbeat (461,880 cases and 361,194 controls), stroke (7,055 cases and 454,825 controls), and coronary heart disease (361,194 cases and 351,037 controls) from United Kingdom biobank. We further carried out heterogeneity and sensitivity analyses. We confirmed the causality of RA with age angina (OR = 1.17, 95% CI: 1.04-1.33, = 1.07E-02), hypertension (OR = 1.45, 95% CI: 1.20-1.75, = 9.64E-05), age heart attack (OR = 1.15, 95% CI: 1.05-1.26, = 3.56E-03), abnormalities of heartbeat (OR = 1.07, 95% CI: 1.01-1.12, = 1.49E-02), stroke (OR = 1.06, 95% CI: 1.01-1.12, = 2.79E-02), and coronary heart disease (OR = 1.19, 95% CI: 1.01-1.39, = 3.33E-02), contributing to the understanding of the overlapping genetic mechanisms and therapeutic approaches between RA and cardiovascular disease.
类风湿性关节炎（RA）与心血管疾病之间存在显著的遗传关联。相关机制包括常见的炎症介质、脂蛋白组成和功能的变化、免疫反应等。然而，RA与血管/心脏问题之间的因果关系仍然未知。在此，我们使用大规模RA全基因组关联研究（GWAS）数据集（462,933例病例和457,732例对照）以及六个心脑血管疾病GWAS数据集进行孟德尔随机化（MR）分析，这些数据集来自英国生物银行，包括老年型心绞痛（461,880例病例和447,052例对照）、高血压（461,880例病例和337,653例对照）、老年型心脏病发作（10,693例病例和451,187例对照）、心跳异常（461,880例病例和361,194例对照）、中风（7,055例病例和454,825例对照）以及冠心病（361,194例病例和351,037例对照）。我们进一步进行了异质性和敏感性分析。我们证实了RA与老年型心绞痛（比值比=1.17，95%置信区间：1.04 - 1.33，P值=1.07×10⁻²）、高血压（比值比=1.45，95%置信区间：1.20 - 1.75，P值=9.64×10⁻⁵）、老年型心脏病发作（比值比=1.15，95%置信区间：1.05 - 1.26，P值=3.56×10⁻³）、心跳异常（比值比=1.07，95%置信区间：1.01 - 1.12，P值=1.49×10⁻²）、中风（比值比=1.06，95%置信区间：1.01 - 1.12，P值=2.79×10⁻²）以及冠心病（比值比=1.19，95%置信区间：1.01 - 1.39，P值=3.33×10⁻²）之间存在因果关系，这有助于理解RA与心血管疾病之间重叠的遗传机制和治疗方法。
