• Mingyi Yang, Yani Su, Ke Xu, Pengfei Wen, Jianbin Guo, Zhi Yang, Lin Liu, and Peng Xu.
• Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, 710054, Xi'an, Shaanxi, China.
• Wien. Klin. Wochenschr. 2024 Jun 20.

ObjectiveTo investigate the genetic level causal association among hyperthyroidism, hypothyroidism, and rheumatoid arthritis (RA).MethodsWe utilized the genome-wide association studies (GWAS) summary data for exposure (hyperthyroidism and hypothyroidism) and outcome (RA) from the IEU OpenGWAS database. We used two different sets of data (test cohort and validation cohort) for causal assessment of exposure and outcome. To establish a causal relationship between these conditions, we conducted a two-sample Mendelian randomization (MR) analysis. Subsequently, we evaluated the MR analysis results for heterogeneity, horizontal pleiotropy, and outliers, aiming to assess the validity and reliability of the findings. Moreover, we conducted additional analyses to examine the robustness of the MR results, including a "Leave one out" analysis and the MR robust adjusted profile score (MR-RAPS) method, ensuring the robustness and adherence to normal distribution assumptions.ResultsThe findings from the test cohort indicated that hyperthyroidism did not exhibit a genetic causal association with RA (P = 0.702, odds ratio [OR] 95% confidence interval [CI] = 1.021 [0.918-1.135]). Conversely, hypothyroidism displayed a positive genetic causal relationship with RA (P < 0.001, OR 95% CI = 1.239 [1.140-1.347]). The analysis results of the validation cohort are consistent with those of the test cohort. Notably, our MR analysis results demonstrated no evidence of heterogeneity, horizontal pleiotropy, or outliers. Furthermore, our MR analysis results remained unaffected by any single nucleotide polymorphism (SNP) and exhibited a normal distribution.ConclusionThe results of this study showed that hypothyroidism was positively correlated with RA, while hyperthyroidism was not causally correlated with RA. Hypothyroidism may as a risk factor of RA should be paid attention to in clinical work. Future studies are needed to further confirm this finding.© 2024. The Author(s).

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