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免疫细胞与瘢痕疙瘩因果关系的孟德尔随机化分析

Mendelian randomization analysis of the causal relationship between immune cells and keloid.

作者信息

Zou Jingwen, Nov Pengkhun, Du Kunpeng

机构信息

Department of Dermatologic Surgery, Dermatology Hospital of Southern Medical University, Guangzhou.

Department of Radiation Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou.

出版信息

Dermatol Reports. 2025 May 23;17(2). doi: 10.4081/dr.2024.10106. Epub 2024 Oct 23.

Abstract

Immune cells play complex roles in the formation of keloid. We aimed to investigate the causal relationship between immune cells and keloid and provide genetic evidence for the association between immune cells and keloid risk. Based on data from a genome-wide association study (GWAS), we performed a comprehensive two-sample Mendelian randomization (MR) analysis of 731 immune cell traits in 481,912 keloid cases. We used the inverse-variance weighting (IVW) method as the primary analysis. Then, a comprehensive sensitivity analysis was adopted to verify the results' robustness, heterogeneity, and horizontal pleiotropy. Finally, reverse MR analysis was performed. The IVW method in forward MR analysis showed that CD66b++ myeloid cell AC was negatively associated with keloid risk (OR<1, p<0.05). Consistently, reverse MR analysis showed that keloid risk was negatively associated with CD66b++ myeloid cell AC (OR=0.85, p=0.012). No significant horizontal pleiotropy or heterogeneity was observed. The results of MR analysis demonstrate a bidirectional causal association between CD66b++ myeloid cell AC and keloid formation, suggesting that CD66b++ myeloid cell AC is a protective factor against keloid.

摘要

免疫细胞在瘢痕疙瘩形成中发挥着复杂作用。我们旨在研究免疫细胞与瘢痕疙瘩之间的因果关系,并为免疫细胞与瘢痕疙瘩风险之间的关联提供遗传学证据。基于全基因组关联研究(GWAS)的数据,我们对481,912例瘢痕疙瘩病例中的731种免疫细胞特征进行了全面的两样本孟德尔随机化(MR)分析。我们采用逆方差加权(IVW)方法作为主要分析方法。然后,采用全面的敏感性分析来验证结果的稳健性、异质性和水平多效性。最后,进行了反向MR分析。正向MR分析中的IVW方法表明,CD66b++髓样细胞AC与瘢痕疙瘩风险呈负相关(OR<1,p<0.05)。同样,反向MR分析表明,瘢痕疙瘩风险与CD66b++髓样细胞AC呈负相关(OR=0.85,p=0.012)。未观察到明显的水平多效性或异质性。MR分析结果表明CD66b++髓样细胞AC与瘢痕疙瘩形成之间存在双向因果关联,提示CD66b++髓样细胞AC是预防瘢痕疙瘩的保护因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d323/12264720/bed1941c4649/dr-17-2-10106-g001.jpg

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