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| 基于孟德尔随机化研究类风湿性关节炎与骨质疏松症的因果关系 |
| Causal relationship between rheumatoid arthritis and osteoporosis: a two-sample Mendelian randomized study |
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| DOI：10.3969/j.issn.1006-7108.2023.12.007 |
| 中文关键词: 类风湿性关节炎 骨质疏松 孟德尔随机化 因果关联 |
| 英文关键词:rheumatoid arthritis osteoporosis Mendelian randomization causal relationship |
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| 中文摘要: |
| 目的 运用两样本孟德尔随机化评估类风湿性关节炎（rheumatoid arthritis，RA）与骨质疏松症（osteoporosis，OP）之间的因果关联。方法 在不同的全基因组关联研究中分别确定暴露和结局的汇总数据。选取与暴露RA相关的全基因组显著性水平（P＜5×10-8）的单核苷酸多态性（single nucleotide polymorphisms，SNPs）作为工具变量（inverse variance weighted，IVs），并去除连锁反应。使用固定效应逆方差加权（IVW）作为MR分析的主要方法，以加权中位数法（WME）和MR-Egger回归法进行补充，并进行敏感性分析以评估结果的稳健性。结果 采用IVW方法发现RA患者发生OP的风险增加（OR=1.11，95% CI：1.04～1.18，P＜0.001），WME结果也进一步表明RA会增加OP的患病风险（OR=1.10，95% CI：1.03～1.18，P=0.007），即RA与OP的发生具有正向相关性。多种敏感性分析显示研究不存在多效性和异质性，说明结果具有稳健性。结论 基因预测RA与OP存在因果关联，对于RA患者可以考虑在疾病早期预防和临床干预OP。 |
| 英文摘要: |
| Objective To evaluate the causal relationship between rheumatoid arthritis (RA) and osteoporosis (OP) using two-sample Mendelian randomization (MR). Methods Summary data on exposure and outcome were obtained from different genome-wide association studies. Single nucleotide polymorphisms (SNPs) that were significantly associated with RA at a genome-wide significance level (P<5×10?8) were selected as instrumental variables (IVs) after linkage disequilibrium removal. Fixed-effect inverse variance weighted (IVW) was utilized as the primary method for MR analysis, with weighted median method (WME) and MR-Egger regression used as complementary methods. Sensitivity analyses were performed to assess the robustness of the results. Result IVW analysis revealed that RA was associated with an increased risk of developing OP (OR=1.11, 95%CI:1.04-1.18, P<0.001). The WME results further supported the positive correlation between RA and OP (OR=1.10, 95%CI:1.03-1.18, P=0.007). Various sensitivity analyses showed no evidence of pleiotropy or heterogeneity, indicating the robustness of the results. Conclusion Our findings suggest a causal relationship between genetic predisposition to RA and OP, and early prevention and clinical intervention for OP should be considered in RA patients. |
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