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| 东亚人群类风湿关节炎与骨质疏松症孟德尔随机化研究 |
| Mendelian randomization of rheumatoid arthritis and osteoporosis in the East Asian population |
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| DOI：10.3969/j.issn.1006-7108.2025.11.008 |
| 中文关键词: 类风湿关节炎 骨质疏松症 孟德尔随机化 因果关联 全基因组关联研究 |
| 英文关键词:rheumatoid arthritis osteoporosis Mendelian randomization causal association genome-wide association studies |
| 基金项目:国家自然科学基金青年项目（82305350）；国家中医药管理局科技项目（GZY-KJS-2025-008）；湖北省自然科学基金项目（2022CFD153）；黄冈市科技创新专项(YBXM20230003-3) |
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| 中文摘要: |
| 目的 通过孟德尔随机化（mendelian randomization, MR）方法研究东亚人群中类风湿关节炎（rheumatoid arthritis, RA）与骨质疏松症 (osteoporosis, OP)的因果关联。方法 从IEU在线数据库获取RA与OP的全基因组关联研究数据集，RA的2个数据集分别来自Japan Biobank机构和UK Biobank机构的汇总数据。OP的数据集来自Japan Biobank机构的汇总数据。逆方差加权（IVW）方法作为主要方法，MR-Egger回归法、加权中位数、简单模式和加权模式作为补充方法来评估RA与OP之间潜在因果关系。先使用两个来源的暴露分别对结局进行MR分析，然后对两次MR结果的IVW方法效应值进行合并计算总效应值，并进行异质性、多效性及敏感性分析。结果 在RA (bbj-a-151)与OP的分析中，IVW方法结果表明RA (bbj-a-151)与OP之间存在因果关联(OR=1.099，95% CI：1.054~1.054，P=8.10×10-6)。在RA (ieu-a-831)与OP的分析中，IVW方法结果表明RA (ieu-a-831)与OP之间亦存在因果关联(OR=1.098，95% CI：1.060~1.137，P=1.43×10-7)。两次的MR分析均不存在异质性和多效性，留一法表明研究结果不会被因移除单一SNP而显著影响。对两次MR结果的IVW方法效应值进行合并，计算总效应值后，结果表明RA与OP之间存在因果关联(OR=1.10，95% CI：1.07~1.13，P＜0.001)。结论 在东亚人群中，RA与OP存在因果关联。 |
| 英文摘要: |
| Objective To investigate the causal association between rheumatoid arthritis (RA) and osteoporosis (OP) in the East Asian population using Mendelian randomization (MR) method. Methods Genome-wide association study datasets for RA and OP were obtained from the IEU online database, with two datasets for RA from the Japan Biobank and UK Biobank respectively, and one dataset for OP from the Japan Biobank. The inverse variance weighted (IVW) method was employed as the primary approach, with MR-Egger regression, weighted median, simple mode, and weighted mode used as supplementary methods to assess the potential causal relationship between RA and OP. MR analyses were initially conducted separately with exposures from two sources and then the IVW method effect estimates from both MR analyses were combined to calculate the overall effect estimate, followed by heterogeneity, multiplicity, and sensitivity analyses. Results In the analysis of RA (bbj-a-151) and OP, the IVW method results indicated a causal association between RA (bbj-a-151) and OP (OR=1.099, 95% CI: 1.054-1.054, P=8.10×10-6). In the analysis of RA (ieu-a-831) and OP, the IVW method results also suggested a causal association between RA (ieu-a-831) and OP (OR=1.098, 95% CI: 1.060-1.137, P=1.43×10-7). Both MR analyses showed no evidence of heterogeneity and multiplicity, and leave-one-out analysis indicated that the results were not significantly influenced by the removal of a single SNP. After combining the IVW method effect estimates from both MR analyses to calculate the overall effect estimate, the results indicated a causal association between RA and OP (OR=1.10, 95% CI: 1.07-1.13, P<0.001). Conclusion In the East Asian population, a causal association exists between RA and OP. |
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