Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: A bidirectional Two-sample mendelian randomization analysis

Author:

Li Wei1,Xu Jing-Wen23,Chai Jin-Lian4,Guo Cong-Cong5,Li Guang-Zheng1,Gao Mei2,Liang Xue-Zhen36

Affiliation:

1. College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Shandong, 250355, China

2. Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Jinan, 250014, China

3. First college of clinical medicine, Shandong University of Traditional Chinese Medicine, Shandong, 250355, China

4. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Shandong, 250355, China

5. Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, 250000, China

6. Orthopaedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong, 250014, China

Abstract

Purpose: Previous studies have explored the role of immune cells on osteonecrosis. This Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on osteonecrosis whether a causal relationship exists and provides some evidence of causality. Methods: The 731 immunocyte phenotypes and osteonecrosis data used in this study were obtained from their respective genome-wide association studies (GWAS). We used inverse variable weighting (IVW) as the primary analysis method. In addition, we simultaneously employed multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, to strengthen the final results. Finally, sensitivity analyses were conducted to verify the stability and feasibility of the data. Results: The results of the IVW method of MR analysis showed that 8 immunocyte phenotypes were positively associated with osteonecrosis (P<0.05, OR > 1); 18 immunocyte phenotypes were negatively associated with osteonecrosis (P<0.05, OR<1), none of which were heterogeneous or horizontally pleiotropic (P > 0.05) or reverse causality. In addition to this, in reverse MR, osteonecrosis was positively associated with 10 additional immunocyte phenotypes (P<0.05, OR > 1) and negatively associated with 14 immunocyte phenotypes (P<0.05, OR<1). And none of them had heterogeneity and horizontal pleiotropy (P > 0.05) or reverse causality. Conclusions: We demonstrated a complex causal relationship between multiple immune phenotypes and osteonecrosis through a comprehensive two-way two-sample MR analysis, highlighting the complex pattern of interactions between the immune system and osteonecrosis.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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