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通过孟德尔随机化、共定位分析和SMR探索免疫细胞与脊柱侧凸之间的关系。

Exploring the Relationship Between Immune Cells and Scoliosis by Mendelian Randomization, Colocalization Analysis, and SMR.

作者信息

Qin Chaofan, Yan Zhengjian, Yu Qingshuai, Chen Mingxin, Hu Tao, Wang Xin, Lei Bo, Chen Yu, Ma Ke, Deng Zhongliang, Cheng Si

机构信息

Department of Orthopedics, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

出版信息

Mediators Inflamm. 2025 Mar 26;2025:8833556. doi: 10.1155/mi/8833556. eCollection 2025.

Abstract

Scoliosis is a condition that can have severe consequences for millions of individuals on an annual basis. Current research in this field is increasingly focusing on the role of the immune system in the development of the disease. However, the precise relationship between immunity and scoliosis remains to be fully elucidated. Our investigation involved a comprehensive Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and scoliosis. The comprehensive univariable MR analysis encompassed 731 immune cells to explore their relationship with scoliosis. Cochran's test, the leave-one-out test, and MR-Egger intercept analysis were used to assess pleiotropy and heterogeneity. We performed multivariable MR analysis to account for potential confounding factors between the immune cells. The colocalization analysis and summary data-based MR (SMR) analysis were utilized to explore relationship between immune cells and cis-eQTL. Our study identified 13 immune cells that were significantly associated with scoliosis by univariable MR, including four risk factors and nine protective factors for scoliosis. In order to reduce confounding between immune cells, multivariable MR was employed, and it was determined that only six immune cell types had independent effects on scoliosis. shared the same variant with CX3CR1 on CD14- CD16-. shared the same variant with CCR2 on CD14- CD16-. , , , and shared the same variant with HLA DR on CD14+ CD16+ monocyte. Our findings suggested a possible link between immune cells and scoliosis and found the key genes for the immune cell, which provides a new direction for further research. However, the specific underlying mechanisms require further investigation in future experiments.

摘要

脊柱侧凸是一种每年会对数以百万计的个体产生严重后果的疾病。该领域目前的研究越来越关注免疫系统在疾病发展中的作用。然而,免疫与脊柱侧凸之间的确切关系仍有待充分阐明。我们的研究涉及全面的孟德尔随机化(MR)分析,以探讨免疫细胞与脊柱侧凸之间的潜在因果关系。全面的单变量MR分析涵盖了731种免疫细胞,以探索它们与脊柱侧凸的关系。使用 Cochr an检验、留一法检验和MR-Egger截距分析来评估多效性和异质性。我们进行了多变量MR分析,以解释免疫细胞之间的潜在混杂因素。利用共定位分析和基于汇总数据的MR(SMR)分析来探索免疫细胞与顺式-eQTL之间的关系。我们的研究通过单变量MR确定了13种与脊柱侧凸显著相关的免疫细胞,包括脊柱侧凸的四个危险因素和九个保护因素。为了减少免疫细胞之间的混杂,采用了多变量MR,并且确定只有六种免疫细胞类型对脊柱侧凸有独立影响。在CD14-CD16-上与CX3CR1共享相同变体。在CD14-CD16-上与CCR2共享相同变体。 、 、 和 在CD14+CD16+单核细胞上与HLA DR共享相同变体。我们的研究结果表明免疫细胞与脊柱侧凸之间可能存在联系,并发现了免疫细胞的关键基因,这为进一步研究提供了新方向。然而,具体的潜在机制需要在未来的实验中进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aff7/11964722/2eac045342fb/MI2025-8833556.001.jpg

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