Causal association between immune cells and sepsis: a based on Mendelian randomization method study
10.3760/cma.j.cn121430-20240527-00462
- VernacularTitle:免疫细胞与脓毒症的因果关联：
- Author:
Qiushuang YU
1
;
Lingxu LI
;
Yina TAO
;
Longqiang ZHANG
;
Junfeng HU
;
Huaxue WANG
Author Information
1. 蚌埠医科大学第一附属医院重症医学科，安徽蚌埠 233004
- Keywords:
Immune cell;
Sepsis;
Mendelian randomization;
Genome-wide association study
- From:
Chinese Critical Care Medicine
2024;36(8):821-828
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the causal association between immune cell and different types of sepsis by using Mendelian randomization (MR) method, and to find the immune cell phenotypes causally associated with sepsis.Methods:Summary data for various circulating immune cell phenotypes were obtained from the GWAS catalog (GCST90001391-GCST90002121). Sepsis data were sourced from the UK Biobank database. Single nucleotide polymorphisms (SNP) were used as instrumental variables. The correlation threshold of P < 5×10 -6 was used to identify the strongly correlated instrumental variables, and the code was used to remove the linkage disequilibrium and the instrumental variables with F-value < 10. Inverse variance weighting (IVW) was used as the main research method to evaluate the stability and reliability of the results, including Cochran's Q test, MR-Egger regression and Leave one out. Reverse MR analysis was performed based on the immunophenotypic results of the removal of horizontal pleiotropy, and the immune cell phenotype with one-way causal association was obtained. Odds ratio ( OR) and 95% confidence interval (95% CI) were used to represent the effect value of the results. Results:CD16 on CD14 -CD16 + monocyte had horizontal pleiotropy in sepsis ( OR = 0.965?4, 95% CI was 0.933?5-0.998?3, P = 0.039?6). There were five immunophenotypes that had reverse causal associations with the types associated with sepsis. After excluding immune cell phenotypes with horizontal pleiotropy and reverse causation, a total of 42 immune cell phenotypes with sepsis, 36 immune cell phenotypes with sepsis (28-day death in critical care), 32 immune cell phenotypes with sepsis (critical care), 44 immune cell phenotypes with sepsis (28-day death), and 30 immune cell phenotypes had potential causal associations with sepsis (under 75 years old). After false discovery rate (FDR) correction, the correlations between BAFF-R on IgD - CD38br and sepsis (28-day death) were negative and strong ( OR = 0.737?8, 95% CI was 0.635?9-0.856?0, P = 6.05×10 -5, PFDR = 0.044?2). Conclusion:A variety of immune cell phenotypes may have a protective effect on sepsis, especially BAFF-R on IgD - CD38br expression is negatively correlated with sepsis (28-day death), which provides a new idea for immune modulation therapy in sepsis.
