A study reveals bidirectional links between thyroid function and rheumatoid arthritis

A recent study published in Frontiers in Immunology has established a groundbreaking bidirectional relationship between thyroid function and the development of rheumatoid arthritis (RA). This two-sample Mendelian randomization (MR) study sheds light on the causative connection between hypothyroidism, hyperthyroidism, and RA, offering novel insights into their interconnectedness. 

Gu et al. conducted the comprehensive two-sample bidirectional MR study utilizing data from diverse genome-wide association studies (GWAS) focusing on thyroid function and RA. Their analysis involved hypothyroidism (N=213,390), Graves’ disease (n=199,034), other hyperthyroidism types (n=190,799), free thyroxine (FT4, n=49,269), and thyroid-stimulating hormone (TSH, n=54,288) as key thyroid function indicators, while RA (n=58,284) was the outcome of interest. 

Forward MR analysis highlighted a genetic predisposition to hypothyroidism, which significantly correlated with an increased risk of RA (ORIvw=1.758, P=7.61×10-5). Conversely, the reverse MR analysis underscored intriguing association of genetic susceptibility to RA elevated the risk of hypothyroidism (ORIvw=1.274, P=3.88×10-20), Graves’ disease (ORIvw=1.269, P=8.15×10-05), and other forms of hyperthyroidism (ORIvw=1.141, P=1.80×10-03). However, no substantial evidence was found supporting a causal relationship, either forward or reverse, between genetic susceptibility to RA and free thyroxine or TSH levels. 

The findings of a multicenter cross-sectional study involving 3,286 individuals reported that those with Graves’ disease or Hashimoto’s thyroiditis exhibited a significantly increased relative risk for other autoimmune conditions, with RA emerging as the most prevalent among them. This study sheds light on the substantial association between thyroid disorders and the increased likelihood of developing RA within this patient population. 

Furthermore, a comprehensive systematic review and meta-analysis conducted in 2022 analyzed data from 29 observational studies involving 35,708 RA patients. The results of this extensive review noted that individuals diagnosed with RA had an elevated risk of experiencing thyroid dysfunction, particularly for hypothyroidism. 

 The study findings emphasize a significant bidirectional causal link between thyroid function and RA, providing valuable new insights into the understanding, screening, and management of these interconnected conditions. However, further investigation is essential to unveil the intricate mechanisms connecting thyroid function and RA. Large-scale randomized controlled trials and scientific animal experiments are crucial to validate this association, paving the way for more targeted and effective approaches to address this comorbidity. 


  1. Gu P, Pu B, Ma Y, Yue D, Xin Q, Li H, et al. Appraising the causal relationship between thyroid function and rheumatoid arthritis: a two-sample bidirectional Mendelian randomization study. Front Immunol. 2023;14:1238757.  
  1. Liu YJ, Miao HB, Lin S, Chen Z. Association between rheumatoid arthritis and thyroid dysfunction: A meta-analysis and systematic review. Front Endocrinol (Lausanne). 2022;13:1015516.  
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