Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Meishan Hospital of Traditional Chinese Medicine, Affiliated Meishan Hospital of Chengdu University of Traditional Chinese Medicine, Meishan, China.
Front Immunol. 2023 Aug 2;14:1146261. doi: 10.3389/fimmu.2023.1146261. eCollection 2023.
Though significant correlations between rheumatoid arthritis (RA) and hypothyroidism have been found in earlier observational studies, their underlying causal relationship is still unknown. Mendelian randomization (MR) was used in the current study to assess the bidirectional causation between RA and hypothyroidism.
We gathered summary data from genome-wide association studies (GWASs) of RA and hypothyroidism in people of European descent. Then, using data from the FinnGen consortium, we replicated our findings. Three approaches were employed to assess the causal link between RA and hypothyroidism: MR-Egger, weighted median (WM), and inverse variance weighted (IVW). The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, the leave-one-out method, and the Cochran's Q test.
The study looked at a bidirectional incidental relationship between RA and hypothyroidism. The risk of hypothyroidism increased with RA (IVW odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.18-1.39, = 8.30E-10), as did the risk of secondary hypothyroidism (IVW OR = 1.12, 95% CI = 1.05-1.21, = 9.64E-4). The results of reverse MR analysis revealed that hypothyroidism (IVW OR = 1.68, 95% CI = 1.51-1.88, = 4.87E-21) and secondary hypothyroidism (IVW OR = 1.74, 95% CI = 1.50-2.01, = 1.91E-13) were linked to an increased risk of RA. Additionally, we obtain the same results in the duplicated datasets as well, which makes our results even more reliable. This study revealed no evidence of horizontal pleiotropy.
The present study established a bidirectional causal link between RA and hypothyroidism. However, it differs slightly from the findings of prior observational studies, suggesting that future research should concentrate on the interaction mechanisms between RA and hypothyroidism.
虽然早期的观察性研究发现类风湿关节炎(RA)与甲状腺功能减退症之间存在显著相关性,但它们之间的因果关系尚不清楚。本研究采用孟德尔随机化(MR)方法来评估 RA 和甲状腺功能减退症之间的双向因果关系。
我们收集了欧洲裔人群中 RA 和甲状腺功能减退症的全基因组关联研究(GWAS)的汇总数据。然后,利用芬兰人基因联盟(FinnGen consortium)的数据对我们的发现进行了复制。采用 MR-Egger、加权中位数(WM)和逆方差加权(IVW)三种方法评估 RA 和甲状腺功能减退症之间的因果关系。使用多种技术(包括 MR-Egger 截距、MR-PRESSO 方法、逐个排除法和 Cochran's Q 检验)来检验偏倚和异质性。
本研究探讨了 RA 和甲状腺功能减退症之间双向的偶发关系。RA 患者发生甲状腺功能减退症的风险增加(IVW 比值比(OR)=1.28,95%置信区间(CI)=1.18-1.39, = 8.30E-10),继发性甲状腺功能减退症的风险也增加(IVW OR = 1.12,95% CI = 1.05-1.21, = 9.64E-4)。反向 MR 分析的结果表明,甲状腺功能减退症(IVW OR = 1.68,95% CI = 1.51-1.88, = 4.87E-21)和继发性甲状腺功能减退症(IVW OR = 1.74,95% CI = 1.50-2.01, = 1.91E-13)与 RA 风险增加相关。此外,我们在重复数据集也得到了相同的结果,这使得我们的结果更加可靠。本研究未发现水平性偏倚的证据。
本研究确立了 RA 和甲状腺功能减退症之间的双向因果关系。然而,与之前的观察性研究结果略有不同,这表明未来的研究应集中于 RA 和甲状腺功能减退症之间的相互作用机制。