To analyze whether there is a potential causal association between inflammatory cytokines and various tendinopathies, including Achilles tendonitis, bicipital tendinitis, calcific tendinitis of the shoulder, gluteal tendinitis, and patellar tendinitis.

In this study, single nucleotide polymorphisms from the data of a large-scale genome-wide association study were selected as instrumental variables, and bidirectional Mendelian randomization as well as multivariate Mendelian randomization, were used to investigate the causal effects of inflammatory cytokines and the risk of developing Achilles tendonitis, Bicipital tendinitis, Calcific tendinitis of shoulder, Gluteal tendinitis and Patellar tendinitis.

In forward Mendelian analyses, monocyte chemotactic protein-3（OR=0.896,95% CI:0.806-0.995） and vascular endothelial growth factor（OR=0.917,95% CI:0.845-0.995） were potential protective factors for Achilles tendonitis, and monokine induced by interferon-γ（OR=1.158,95% CI:1.029-1.302） was a potential risk factor for Achilles tendonitis. Monocyte chemotactic protein-3（OR=1.214,95% CI:1.034-1.426）was a potential risk factor for Bicipital tendinitis, while hepatocyte growth factor （OR=0.661,95% CI:0.489-0.893） as a potential protective factor for Bicipital tendinitis. Hepatocyte growth factor （OR=0.730,95% CI:0.557-0.957）was a potential protective factor for Calcific tendinitis of shoulder. Interleukin-13 （OR=0.828,95% CI:0.714-0.960） was a potential protective factor for Gluteal tendinitis. Interleukin-8 （OR=0.649,95% CI:0.444-0.949） as a Patellar tendinitis potential protective factor and tumor necrosis factor-α （OR=1.707,95% CI:1.085-2.685）was a potential risk factor for Patellar tendinitis. In multivariate Mendelian analysis, hepatocyte growth factor（OR=0.687,95% CI:0.511-0.924） remained a protective factor for Bicipital tendinitis. Sensitivity analyses showed that the main analyses were robust without outliers, with no significant outliers, heterogeneity, or horizontal pleiotropy.

The study suggests a potential causal relationship between inflammatory cytokines and the five tendon diseases investigated.