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Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization.

Publication ,  Journal Article
Tan, Y; Yao, H; Lin, C; Lai, Z; Li, H; Zhang, J; Fu, Y; Wu, X; Yang, G; Feng, L; Jing, C
Published in: Arthritis Care Res (Hoboken)
March 31, 2024

OBJECTIVE: Rheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co-occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods. METHODS: Bidirectional two-sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function trait data sets from the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR-BMA) was performed to adjust for possible competing risk factors. A sensitivity data set, which included data from patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions. RESULTS: A significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD) as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR-BMA results showed that RA and AITD were independent risk factors in their bidirectional causality, even in the presence of other competing risk factors (adjusted P < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them. CONCLUSION: Our results illustrate the significant bidirectional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in patients with RA deserves further attention, and vice versa.

Duke Scholars

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Published In

Arthritis Care Res (Hoboken)

DOI

EISSN

2151-4658

Publication Date

March 31, 2024

Location

United States

Related Subject Headings

  • 4201 Allied health and rehabilitation science
  • 3202 Clinical sciences
  • 1701 Psychology
  • 1117 Public Health and Health Services
  • 1103 Clinical Sciences
 

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Tan, Y., Yao, H., Lin, C., Lai, Z., Li, H., Zhang, J., … Jing, C. (2024). Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization. Arthritis Care Res (Hoboken). https://doi.org/10.1002/acr.25335
Tan, Yuxuan, Huojie Yao, Chuhang Lin, Zhengtian Lai, Haiying Li, Jing Zhang, Yingyin Fu, et al. “Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization.Arthritis Care Res (Hoboken), March 31, 2024. https://doi.org/10.1002/acr.25335.
Tan, Yuxuan, et al. “Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization.Arthritis Care Res (Hoboken), Mar. 2024. Pubmed, doi:10.1002/acr.25335.
Tan Y, Yao H, Lin C, Lai Z, Li H, Zhang J, Fu Y, Wu X, Yang G, Feng L, Jing C. Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization. Arthritis Care Res (Hoboken). 2024 Mar 31;
Journal cover image

Published In

Arthritis Care Res (Hoboken)

DOI

EISSN

2151-4658

Publication Date

March 31, 2024

Location

United States

Related Subject Headings

  • 4201 Allied health and rehabilitation science
  • 3202 Clinical sciences
  • 1701 Psychology
  • 1117 Public Health and Health Services
  • 1103 Clinical Sciences