Muqing Niu,1 Jinyong Pan,2,3 Kui Wang,4 Li Zhang,2 Zhaotang Lin,2 Fengling Zhang1,2 

1The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, People’s Republic of China; 2Department of Pediatrics, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, People’s Republic of China; 3Clinical Medical Research Center for Children’s Diseases in the Xinjiang Production and Construction Corps, Shihezi, Xinjiang, People’s Republic of China; 4Shihezi University School of Medicine, Shihezi, Xinjiang, People’s Republic of China

Correspondence: Jinyong Pan, Department of Pediatrics, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, People’s Republic of China, Email 63620441@qq.com

Background: Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is a systemic immune vasculitis with an unclear etiology. It is often complicated by coronary artery disease. This study uses bidirectional Mendelian randomization (MR) to investigate the interaction between KD and circulating inflammatory factors, providing insights into their causal relationships.
Methods: We conducted a two-way pooled MR analysis to examine the causal links between 41 circulating inflammatory regulators and the risk of KD. Genetic data related to inflammation were sourced from three genome-wide association studies (GWASs) involving CRP, PCT, and cytokines, while KD data were derived from other studies. Inverse-variance weighting (IVW) was the primary MR method, with sensitivity analyses performed using MR‒Egger, weighted median, weighted mode, and MR–PRESSO to ensure robustness.
Results: Forward MR analyses showed no significant relationship between inflammatory factors and KD outcomes. In contrast, reverse MR, with KD as the exposure factor, revealed that interleukin-2 (IL-2) and interleukin-8 (IL-8) were significantly associated with KD (IL-2: OR=1.0085, P=0.037; IL-8: OR=1.0099, P=0.014). Borderline significant associations were observed for factors such as B_NGF, EOTAXIN, HGF, and IL_12_P70 in MR‒Egger and weighted median analyses.
Conclusion: This bidirectional MR study highlights the role of circulating inflammatory modulators in KD risk, offering insights into KD pathogenesis and potential therapeutic targets.

Keywords: bidirectional Mendelian randomization, circulating inflammatory regulators, Mendelian randomization, Kawasaki disease, GWAS catalog