Department of Orthopedics, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Gongshu District, Hangzhou, Zhejiang Province, China.
Medicine (Baltimore). 2024 Aug 16;103(33):e39319. doi: 10.1097/MD.0000000000039319.
Past observational studies have documented an association between rheumatoid arthritis (RA) and chronic respiratory diseases. Undertaking the approach of Mendelian randomization (MR) analysis, this research aims to delve deeper into the probability of a causal connection between RA and chronic respiratory diseases. Collated genome-wide association study data covering RA with 4199 cases against 208,254 controls, asthma comprising 8216 cases versus 201,592 controls, and chronic obstructive pulmonary disease (COPD) detailing 3315 cases in contrast to 201,592 controls were derived from the repository of the Japanese Biobank. A selection of 10 RA-related, 8 asthma-related, and 4 COPD-related single nucleotide polymorphisms notable for their statistical significance (P < 5 × 10-8) were identified as instrumental variables. The primary analytical technique was the inverse variance-weighted (IVW) method, alongside the MR-Egger protocol, weighted median, and weighted mode to reinforce the validity and solidity of the principal results. For scrutinizing possible implications of horizontal pleiotropy, we harnessed the MR-Egger intercept examination and the Mendelian Randomization Pleiotropy REsidual Sum and Outlier test. Employing the inverse variance-weighted technique, we established a positive correlation between genetic predispositions for RA and actual occurrences of asthma (odds ratios [OR] = 1.14; 95% confidence intervals [CI]: 1.04-1.24; P = .003). This correlation remained strong when testing the results utilizing various methods, including the MR-Egger method (OR = 1.32; 95% CI: 1.09-1.60; P = .023), the weighted median (OR = 1.16; 95% CI: 1.06-1.26; P < .001), and the weighted mode (OR = 1.21; 95% CI: 1.11-1.32; P = .002). Furthermore, our findings from the inverse variance-weighted method also demonstrated a positive association between genetically predicted RA and COPD (OR = 1.12; 95% CI: 1.02-1.29; P = .021). However, no such link was discerned in supplementary analyses. In a shifted perspective-the reverse MR analysis-no correlation was identified between genetically predicted instances of asthma (IVW, P = .717) or COPD (IVW, P = .177) and RA. The findings confirm a causal correlation between genetically predicted RA and an elevated risk of either asthma or COPD. In contrast, our results offer no support to the presumed causal relationship between genetic susceptibility to either asthma or COPD and the subsequent development of RA.
过去的观察性研究已经证明类风湿关节炎（RA）与慢性呼吸道疾病之间存在关联。本研究采用孟德尔随机化（MR）分析的方法，深入探讨 RA 与慢性呼吸道疾病之间是否存在因果关系。该研究整合了来自日本生物银行的全基因组关联研究数据，包括 4199 例 RA 病例对照 208254 例，8216 例哮喘病例对照 201592 例，3315 例慢性阻塞性肺疾病（COPD）病例对照 201592 例。选择了 10 个与 RA 相关、8 个与哮喘相关、4 个与 COPD 相关的单核苷酸多态性，这些多态性具有统计学意义（P<5×10-8），被确定为工具变量。主要分析技术是逆方差加权（IVW）法，同时还使用了 MR-Egger 协议、加权中位数和加权模式，以加强主要结果的有效性和稳健性。为了检查可能存在的水平多效性影响，我们利用了 MR-Egger 截距检验和 Mendelian Randomization Pleiotropy REsidual Sum and Outlier test。采用逆方差加权技术，我们发现 RA 的遗传易感性与实际哮喘发病之间存在正相关（比值比[OR] = 1.14；95%置信区间[CI]：1.04-1.24；P = 0.003）。当使用各种方法（包括 MR-Egger 方法，OR = 1.32；95% CI：1.09-1.60；P = 0.023）、加权中位数（OR = 1.16；95% CI：1.06-1.26；P<0.001）和加权模式（OR = 1.21；95% CI：1.11-1.32；P = 0.002）时，该结果仍然很强。此外，我们使用逆方差加权法的结果还表明，遗传预测的 RA 与 COPD 之间存在正相关（OR = 1.12；95% CI：1.02-1.29；P = 0.021）。然而，在补充分析中没有发现这种联系。在反向 MR 分析中，我们没有发现遗传预测的哮喘（IVW，P = 0.717）或 COPD（IVW，P = 0.177）与 RA 之间存在相关性。这些发现证实了遗传预测的 RA 与哮喘或 COPD 风险增加之间存在因果关系。相反，我们的结果不支持哮喘或 COPD 遗传易感性与随后 RA 发展之间假定的因果关系。
