Two-sample Mendelian randomization analysis of the causal relationship between human immune cell phenotypes and keloids
10.3760/cma.j.cn501225-20231130-00219
- VernacularTitle:人免疫细胞表型与瘢痕疙瘩之间因果关系的双样本孟德尔随机化分析
- Author:
Wenjun GAN
1
;
Jingru WANG
;
Jia HE
;
Xiaodong CHEN
Author Information
1. 广东医科大学第一临床医学院，湛江 524023
- Publication Type:Journal Article
- Keywords:
Keloid;
Immunity, cellular;
Mendelian randomization analysis;
Immune system;
Databases, genetic;
Causality
- From:
Chinese Journal of Burns
2025;41(1):84-93
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the causal relationship between human immune cell phenotypes and keloids.Methods:This study was based on a two-sample Mendelian randomization (MR) analysis. Human immune cell phenotypes were considered as the exposure factors, and keloid was the outcome. Data on immune cell phenotypes (3 757 samples) and keloids (668 samples) were obtained from the genome-wide association study database. Using single nucleotide polymorphisms (SNPs) significantly associated with immune cell phenotypes as instrumental variables with the influence of weak instrumental variables being excluded, two-sample MR analysis was employed to evaluate the causal relationship between 731 human immune cell phenotypes and keloids. The inverse variance weighted (IVW) method was used to infer causal relationships, and the MR-Egger, weighted median, and weighted mode methods were used for validation. For SNPs of immune cell phenotypes meeting the hypothesis, the Cochran Q test was used to assess heterogeneity, and the MR-Egger regression and MR-PRESSO outlier tests were used to evaluate horizontal pleiotropy.Results:A total of 18 204 SNPs meeting the significant threshold ( P<1×10??) were selected as instrumental variables for 731 immune cell phenotypes, and none of these SNPs were weak instrumental variables (with F values all >10). According to the IVW method, 21 immune cell phenotypes were identified with potential causal relationships to keloids, among which the CD62L - monocyte absolute count, CD19 on naive-mature B cell, CD19 on IgD + B cell, CD27 on plasma blast-plasma cell, CD86 on CD62L + myeloid dendritic cell, CD45 on natural killer T cell, CD25 on CD39 + CD4 + regulatory T cell, CD45 on monocytic myeloid-derived suppressor cells, CD8 on effector memory CD8 + T cell, and CD45RA on resting CD4 + regulatory T cell showed significant positive correlations with keloids (with odds ratios of 1.12, 1.09, 1.08, 1.21, 1.13, 1.12, 1.17, 1.11, 1.10, and 1.07, respectively, 95% confidence intervals of 1.03-1.23, 1.02-1.16, 1.01-1.15, 1.06-1.38, 1.02-1.25, 1.01-1.24, 1.03-1.33, 1.00-1.23, 1.00-1.20, and 1.01-1.13, respectively, P<0.05), while the activated and secreted CD4 + regulatory T cell absolute count, CD25 on unswitched memory B cell, plasmacytoid dendritic cell absolute count, CD14 on monocytic myeloid-derived suppressor cells, CD8 on natural killer T cell, CD20 on IgD + CD38 + B cell, CD11c + CD62L - monocyte absolute count, CD66b ++ myeloid cell absolute count, CD11c on granulocytes, CD14 on CD14 + CD16 + monocyte, and CD3 on central memory CD8 + T cell showed significant negative correlations with keloids (with odds ratios of 0.95, 0.93, 0.93, 0.93, 0.91, 0.89, 0.89, 0.88, 0.87, 0.86, and 0.85, respectively, 95% confidence intervals of 0.90-1.00, 0.87-0.99, 0.88-0.99, 0.87-0.99, 0.84-1.00, 0.81-0.98, 0.81-0.98, 0.79-0.99, 0.78-0.96, 0.75-0.99, and 0.74-0.96, respectively, P<0.05). MR-Egger method confirmed the potential causal relationship existing respectively between CD25 on CD39 + CD4 + regulatory T cell, CD86 on CD62L + myeloid dendritic cell, CD19 on IgD + B cell, CD45RA on resting CD4 + regulatory T cell, CD3 on central memory CD8 + T cell and keloids (with odds ratios of 1.32, 1.22, 1.11, 1.09, and 0.73, respectively, 95% confidence intervals of 1.03-1.70, 1.04-1.44, 1.02-1.21, 1.01-1.19, and 0.55-0.95, respectively, P<0.05). The weighted median method confirmed the potential causal relationship existing respectively between CD45 on natural killer T cell, activated and secreted CD4 + regulatory T cells absolute count, CD20 on IgD + CD38 + B cell, CD66b ++ myeloid cell absolute count and keloids (with odds ratios of 1.15, 0.93, 0.87, and 0.83, respectively, 95% confidence intervals of 1.01-1.31, 0.86-1.00, 0.77-0.98, and 0.71-0.96, respectively, P<0.05). Among them, the potential causal relationship between CD20 on IgD + CD38 + B cell and keloids was further verified by the weighted mode method (with odds ratio of 0.86, 95% confidence interval of 0.77-0.97, P<0.05). According to the aforementioned IVW method analysis results, the SNPs associated with the 21 immune cell phenotypes that had a significant causal relationship with keloids showed no significant heterogeneity ( P>0.05) or significant horizontal pleiotropy ( P>0.05). Conclusions:From a genetic perspective, the potential causal relationships between 21 human immune cell phenotypes and keloids have been revealed, of which 10 immune cell phenotypes may be risk factors for keloids, while 11 immune cell phenotypes may act as protective factors for keloids.
