Yang Leilei, Wang Xiaoqin, Gu Bingjie, Su Dinglei
Department of Rheumatology and Immunology, Nanjing First Hospital, Nanjing Medical University, No. 68 Changle Road, Nanjing, 210006, Jiangsu, China.
Clin Rheumatol. 2025 Jan;44(1):153-160. doi: 10.1007/s10067-024-07258-y. Epub 2024 Dec 6.
Epidemiological and observational studies have indicated an association between rheumatoid arthritis (RA) and pulmonary arterial hypertension (PAH). However, consistent conclusions have not been reached due to various limitations. In order to determine whether RA and PAH are causally related, we conducted a Mendelian randomization (MR) study with two samples. Data for overall RA (13,621 cases and 262,844 controls), seropositive RA (5103 cases and 402,554 controls), seronegative RA (4192 cases and 311,210 controls), and PAH (248 cases and 289,117 controls) derived from the FinnGen consortium. The inverse variance weighted, along with four other effective methodologies, were employed to comprehensively infer the causal relationships between RA and PAH. To assess the estimation's robustness, a number of sensitivity studies were performed. Causal genetic association was found between seropositive RA and decreased risk of PAH (odds ratio (OR) = 0.812, 95% confidence interval (CI) = 0.687-0.959, p = 0.042), while no causal relationship was found between overall RA or seronegative RA and PAH (OR = 0.871, 95% CI = 0.645-1.175, p = 0.548; OR = 0.791, 95%CI = 0.471-1.328, p = 0.374, respectively). We are the first to use MR analysis to explore the causal relationship between RA and PAH, revealing a decreased risk of PAH in individuals with seropositive RA. Key Points • There is a notable genetic association between seropositive RA and a decreased risk of developing PAH. • No significant association was observed between overall RA or seronegative RA and the risk of PAH. • RA represents a heterogeneous disease, with its seropositive or seronegative forms exhibiting distinct genetic characteristics.
流行病学和观察性研究表明类风湿性关节炎（RA）与肺动脉高压（PAH）之间存在关联。然而，由于各种局限性，尚未得出一致的结论。为了确定RA和PAH是否存在因果关系，我们进行了一项双样本孟德尔随机化（MR）研究。总体RA（13621例病例和262844例对照）、血清阳性RA（5103例病例和402554例对照）、血清阴性RA（4192例病例和311210例对照）以及PAH（248例病例和289117例对照）的数据来自芬兰基因联盟。采用逆方差加权法以及其他四种有效方法，全面推断RA与PAH之间的因果关系。为评估估计的稳健性，进行了多项敏感性研究。发现血清阳性RA与PAH风险降低之间存在因果遗传关联（优势比（OR）=0.812，95%置信区间（CI）=0.687 - 0.959，p = 0.042），而总体RA或血清阴性RA与PAH之间未发现因果关系（OR分别为0.871，95%CI = 0.645 - 1.175，p = 0.548；OR = 0.791，95%CI = 0.471 - 1.328，p = 0.374）。我们是首个使用MR分析探索RA与PAH因果关系的研究，揭示了血清阳性RA个体患PAH的风险降低。要点：• 血清阳性RA与PAH发病风险降低之间存在显著的遗传关联。• 总体RA或血清阴性RA与PAH风险之间未观察到显著关联。• RA是一种异质性疾病，其血清阳性或血清阴性形式表现出不同的遗传特征。
