Graves' Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study.
Graves' Disease and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study.
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DOI：
10.3389/fendo.2021.702482
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发表时间：
2021
影响因子：
5.2
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wu D;Xian W;Hong S;Liu B;Xiao H;Li Y
Graves病（GD）与类风湿关节炎（RA）的频繁共存已在观察性研究中被引用和讨论，但这两种疾病之间是否存在因果关系仍然是一个问题。我们从BioBank Japan （BBJ）检索了GD和RA的全基因组关联研究（GWAS）汇总数据。选择与感兴趣疾病相关的单核苷酸多态性（snp）作为工具变量（IVs），具有全基因组显著性水平（P < 5.0 × 10−8）。采用随机效应反方差加权法（IVW）对随机效应的因果效应进行组合。采用MR-Egger和加权中位数法敏感性检验分析水平多效性效应。进行留一分析以避免单个SNP引起的偏差。我们的MR结果的统计功率是根据Brion的方法计算的。我们的研究发现了GD和RA之间的双向因果关系。RA的存在可能使GD的风险增加39% （OR 1.39, 95% CI 1.10-1.75, P = 0.007）。同样，GD的存在可能使RA的风险增加30% （OR 1.30, 95% CI 0.94-1.80, P = 0.112）。我们的研究提供了100%的能力来检测RA对GD风险的因果关系，反之亦然。我们发现在亚洲人群中GD和RA之间存在双向因果效应。我们的研究支持在RA患者中筛查GD的临床需要，反之亦然。对GD患者的RA（或RA患者的GD）进行良好管理的潜在益处值得高度重视。此外，新的令人满意的RA药物可能适用于GD，这种潜力值得进一步研究。
The frequent coexistence of Graves’ disease (GD) and rheumatoid arthritis (RA) has been cited and discussed in observational studies, but it remains a question as to whether there is a causal effect between the two diseases. We retrieved genome-wide association study (GWAS) summary data of GD and RA from BioBank Japan (BBJ). Single nucleotide polymorphisms (SNPs) associated with diseases of interest were selected as instrumental variables (IVs) at a genome-wide significance level (P < 5.0 × 10−8). The random-effects inverse variance weighted method (IVW) was used to combine the causal effect of IVs. The horizontal pleiotropy effect was analyzed by MR-Egger and weighted median method sensitivity test. A leave-one-out analysis was conducted to avoid bias caused by a single SNP. The statistical power of our MR result was calculated according to Brion’s method. Our study discovered a bidirectional causal effect between GD and RA. The presence of RA may increase the risk of GD by 39% (OR 1.39, 95% CI 1.10–1.75, P = 0.007). Similarly, the existence of GD may increase the risk of RA by 30% (OR 1.30, 95% CI 0.94–1.80, P = 0.112). Our study provides 100% power to detect the causal effect of RA on GD risk, and vice versa. We found a bidirectional causal effect between GD and RA in an Asian population. Our study supported the clinical need for screening GD in RA patients, and vice versa. The potential benefit of sound management of RA in GD patients (or GD in RA patients) merits excellent attention. Moreover, novel satisfactory medicine for RA may be applicable to GD and such potential is worthy of further investigation.
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