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Volume 40 Issue 6
Jun.  2024
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2024  >  40(6): 572-578
Wu HL,Chen YF,Li ST,et al.Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method[J].Chin J Burns Wounds,2024,40(6):572-578.DOI: 10.3760/cma.j.cn501225-20240203-00046.
Citation: Wu HL,Chen YF,Li ST,et al.Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method[J].Chin J Burns Wounds,2024,40(6):572-578.DOI: 10.3760/cma.j.cn501225-20240203-00046.
shu

Analysis of the causal relationship between human immune cells and hypertrophic scar using two-sample bidirectional Mendelian randomization method

doi: 10.3760/cma.j.cn501225-20240203-00046
  • 1.

    Department of Burn and Wound Repair Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

  • 2.

    Department of Plastic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

Funds:

General Program of National Natural Science Foundation of China 82172213

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    Abstract
  •   Objective  To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.  Methods  This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells.  Results  The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS (PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS (P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS (P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS (P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells (P>0.05).  Conclusions  From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

     

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