Genetically Supported Causality Between Immune Cells Traits and Low Back Pain: A Bi-Directional Two-Sample Mendelian Randomization Study

Jianbing Wang,1,2,&ast; Mengye Zhu,1,3,&ast; Yuhan Liu,4 Daying Zhang,1,3 Shuchun Yu,5 Jinjin Zhang6 1Department of Pain Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Department of Anesthesiology, Jiangxi Cancer Hospital, Nanchang, People’s Republic of China; 3Jiangxi Key Laboratory of Trauma, Burn and Pain Medicine, Nanchang, People’s Republic of China; 4College of Medicine, Jinggangshan University, Ji’an, People’s Republic of China; 5Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 6Department of Pain Medicine, Ji’an Central People’s Hospital, Ji’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinjin Zhang, Department of Pain Medicine, Ji’an Central People’s Hospital, No. 106, Jinggangshan Avenue, Ji’an City, Jiangxi Province, People’s Republic of China, Email [email protected] Shuchun Yu, Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Nanchang, People’s Republic of China, Email [email protected]: Prior studies have suggested that immune cells play a crucial role in Low Back Pain (LBP). We employed a bi-directional Mendelian randomization (MR) study to investigate the causal relationship of immune cells with the risk of LBP.Patients and Methods: Single Nucleotide Polymorphisms (SNPs) that had a significant genetic association with immune cells were used as instrumental variables (IVs). The inverse variance weighted (IVW) method was used as the primary approach for MR analyses. To assess the robustness, sensitivity analyses were further performed using MR-Egger and MR-PRESSO.Results: The MR analysis revealed a causal relationship between six types of immune cells and LBP (P < 0.05), including CD4 Treg AC (OR, 0.925; 95% CI, 0.878– 0.974; P = 0.003), CD19 on CD20− CD38− (OR, 0.938; 95% CI, 0.898– 0.979; P = 0.003), CD4 on HLA DR+ CD4+ (OR, 0.947; 95% CI, 0.909– 0.987; P = 0.010), CD25 on CD39+ CD4+ (OR, 0.954; 95% CI = 0.922– 0.988; P = 0.008), CD14 on CD33br HLA DR+ CD14dim (OR, 0.950; 95% CI = 0.916– 0.985; P = 0.006), and CD4RA on TD CD4+ (OR, 1.030; 95% CI, 1.012– 1.048; P = 0.001). Reverse MR analysis found no evidence of potential causal effects of genetically predicted LBP on the six types of immune cells.Conclusion: This study has demonstrated a close genetic connection between immune cells and LBP, providing valuable insights for future clinical research.Keywords: immune cells, low back pain, Mendelian randomization