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类风湿关节炎与东亚人群间质性肺病的因果关系:两样本孟德尔随机化研究。

The causal relationship between rheumatoid arthritis and interstitial lung disease in East Asian population: A two-sample Mendelian randomization study.

机构信息

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

出版信息

Medicine (Baltimore). 2024 Oct 4;103(40):e39903. doi: 10.1097/MD.0000000000039903.

Abstract

To investigate the causal relationship between rheumatoid arthritis (RA) and interstitial lung disease (ILD) in the East Asian population, we utilized Mendelian randomization (MR). Publicly available summarized data from genome-wide association studies on RA (4199 cases and 208,254 controls), and the data on ILD (1046 cases and 176,974 controls) were obtained from BioBank Japan. Eligible single nucleotide polymorphisms from East Asian populations were obtained from genome-wide association studies as instrumental variables, and 11 RA-related single nucleotide polymorphisms (P < 5 × 10-8) were selected as instrumental variables. MR analysis was performed using inverse variance weighted, MR-Egger regression, weighted median, and MR-PRESSO with RA as the exposure data and ILD as the outcome data. Reliability was evaluated using Cochran Q test, MR-Egger intercept, leave-one-out analysis, and funnel plot. Inverse variance weighted results showed an odds ratio (95% confidence interval) of 1.29 (1.18-1.41), P = 3.99 × 10-8, indicating a positive association between RA and ILD. The reliability evaluation could adopt the fixed-effect model, and the absolute value of the MR-Egger regression intercept was 0.021, P > 0.05, and P value of Global Test in MR-PRESSO was 0.573. The test results of the leave-one-out showed that the results are robust, and the funnel plot indicated that the instrumental variables were not affected by potential factors. In conclusion, this study demonstrates that RA is a risk factor for ILD in the East Asian population.

摘要

为了探究类风湿关节炎(RA)与间质性肺疾病(ILD)在东亚人群中的因果关系,我们利用了孟德尔随机化(MR)方法。RA 的全基因组关联研究(4199 例病例和 208254 例对照)和ILD 的汇总数据(1046 例病例和 176974 例对照)均来自日本生物银行。将来自全基因组关联研究的、适合东亚人群的单核苷酸多态性作为工具变量,选择 11 个与 RA 相关的单核苷酸多态性(P < 5 × 10-8)作为工具变量。采用逆方差加权法、MR-Egger 回归、加权中位数和 MR-PRESSO 方法,以 RA 为暴露数据,ILD 为结局数据进行 MR 分析。采用 Cochran Q 检验、MR-Egger 截距、逐一剔除分析和漏斗图来评估可靠性。逆方差加权结果显示,RA 和 ILD 之间存在正相关,比值比(95%置信区间)为 1.29(1.18-1.41),P = 3.99 × 10-8。可靠性评估可以采用固定效应模型,MR-Egger 回归截距的绝对值为 0.021,P > 0.05,MR-PRESSO 中的全局检验 P 值为 0.573。逐一剔除分析的检验结果表明,结果稳健,漏斗图表明工具变量不受潜在因素影响。综上所述,本研究表明 RA 是东亚人群中 ILD 的一个危险因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b8c/11460934/1f18399d358e/medi-103-e39903-g001.jpg

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