Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study
BackgroundAutoimmune diseases exhibit heterogenous dysregulation of pro-inflammatory or anti-inflammatory cytokine expression, akin to the pathophysiology of sepsis. It is speculated that individuals with autoimmune diseases may have an increased likelihood of developing sepsis and face elevated mor...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2024.1331950/full |
| _version_ | 1797346141302423552 |
|---|---|
| author | Xin Tie Yanjie Zhao Jing Su Xing Liu Tongjuan Zou Wanhong Yin |
| author_facet | Xin Tie Yanjie Zhao Jing Su Xing Liu Tongjuan Zou Wanhong Yin |
| author_sort | Xin Tie |
| collection | DOAJ |
| description | BackgroundAutoimmune diseases exhibit heterogenous dysregulation of pro-inflammatory or anti-inflammatory cytokine expression, akin to the pathophysiology of sepsis. It is speculated that individuals with autoimmune diseases may have an increased likelihood of developing sepsis and face elevated mortality risks following septic events. However, current observational studies have not yielded consistent conclusions. This study aims to explore the causal relationship between autoimmune diseases and the risks of sepsis and mortality using Mendelian randomization (MR) analysis.MethodsWe conducted a two-sample MR study involving a European population, with 30 autoimmune diseases as the exposure factors. To assess causal relationships, we employed the inverse variance-weighted (IVW) method and used Cochran's Q test for heterogeneity, as well as the MR pleiotropy residual sum and outlier (MR-PRESSO) global test for potential horizontal pleiotropy.ResultsGenetically predicted Crohn's disease (β = 0.067, se = 0.034, p = 0.046, OR = 1.069, 95% CI = 1.001–1.141) and idiopathic thrombocytopenic (β = 0.069, se = 0.031, p = 0.023, OR = 1.071, 95% CI = 1.009–1.136) were positively associated with an increased risk of sepsis in critical care. Conversely, rheumatoid arthritis (β = −0.104, se = 0.047, p = 0.025, OR = 0.901, 95% CI = 0.823–0.987), ulcerative colitis (β = −0.208, se = 0.084, p = 0.013, OR = 0.812, 95% CI = 0.690–0.957), and narcolepsy (β = −0.202, se = 0.092, p = 0.028, OR = 0.818, 95% CI = 0.684–0.978) were associated with a reduced risk of sepsis in critical care. Moreover, Crohn's disease (β = 0.234, se = 0.067, p = 0.001, OR = 1.263, 95% CI = 1.108–1.440) and idiopathic thrombocytopenic (β = 0.158, se = 0.061, p = 0.009, OR = 1.171, 95% CI = 1.041–1.317) were also linked to an increased risk of 28-day mortality of sepsis in critical care. In contrast, multiple sclerosis (β = −0.261, se = 0.112, p = 0.020, OR = 0.771, 95% CI = 0.619–0.960) and narcolepsy (β = −0.536, se = 0.184, p = 0.003, OR = 0.585, 95% CI = 0.408–0.838) were linked to a decreased risk of 28-day mortality of sepsis in critical care.ConclusionThis MR study identified causal associations between certain autoimmune diseases and risks of sepsis in critical care, and 28-day mortality in the European population. These findings suggest that exploring the mechanisms underlying autoimmune diseases may offer new diagnostic and therapeutic strategies for sepsis prevention and treatment. |
| first_indexed | 2024-03-08T11:27:30Z |
| format | Article |
| id | doaj.art-0ca8b7936e7743d2bb723c5b47c9a3e7 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-08T11:27:30Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-0ca8b7936e7743d2bb723c5b47c9a3e72024-01-26T04:44:54ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-01-011110.3389/fmed.2024.13319501331950Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization studyXin Tie0Yanjie Zhao1Jing Su2Xing Liu3Tongjuan Zou4Wanhong Yin5Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundAutoimmune diseases exhibit heterogenous dysregulation of pro-inflammatory or anti-inflammatory cytokine expression, akin to the pathophysiology of sepsis. It is speculated that individuals with autoimmune diseases may have an increased likelihood of developing sepsis and face elevated mortality risks following septic events. However, current observational studies have not yielded consistent conclusions. This study aims to explore the causal relationship between autoimmune diseases and the risks of sepsis and mortality using Mendelian randomization (MR) analysis.MethodsWe conducted a two-sample MR study involving a European population, with 30 autoimmune diseases as the exposure factors. To assess causal relationships, we employed the inverse variance-weighted (IVW) method and used Cochran's Q test for heterogeneity, as well as the MR pleiotropy residual sum and outlier (MR-PRESSO) global test for potential horizontal pleiotropy.ResultsGenetically predicted Crohn's disease (β = 0.067, se = 0.034, p = 0.046, OR = 1.069, 95% CI = 1.001–1.141) and idiopathic thrombocytopenic (β = 0.069, se = 0.031, p = 0.023, OR = 1.071, 95% CI = 1.009–1.136) were positively associated with an increased risk of sepsis in critical care. Conversely, rheumatoid arthritis (β = −0.104, se = 0.047, p = 0.025, OR = 0.901, 95% CI = 0.823–0.987), ulcerative colitis (β = −0.208, se = 0.084, p = 0.013, OR = 0.812, 95% CI = 0.690–0.957), and narcolepsy (β = −0.202, se = 0.092, p = 0.028, OR = 0.818, 95% CI = 0.684–0.978) were associated with a reduced risk of sepsis in critical care. Moreover, Crohn's disease (β = 0.234, se = 0.067, p = 0.001, OR = 1.263, 95% CI = 1.108–1.440) and idiopathic thrombocytopenic (β = 0.158, se = 0.061, p = 0.009, OR = 1.171, 95% CI = 1.041–1.317) were also linked to an increased risk of 28-day mortality of sepsis in critical care. In contrast, multiple sclerosis (β = −0.261, se = 0.112, p = 0.020, OR = 0.771, 95% CI = 0.619–0.960) and narcolepsy (β = −0.536, se = 0.184, p = 0.003, OR = 0.585, 95% CI = 0.408–0.838) were linked to a decreased risk of 28-day mortality of sepsis in critical care.ConclusionThis MR study identified causal associations between certain autoimmune diseases and risks of sepsis in critical care, and 28-day mortality in the European population. These findings suggest that exploring the mechanisms underlying autoimmune diseases may offer new diagnostic and therapeutic strategies for sepsis prevention and treatment.https://www.frontiersin.org/articles/10.3389/fmed.2024.1331950/fullsepsisautoimmune diseasesMendelian randomization28-day mortalityrisk factor |
| spellingShingle | Xin Tie Yanjie Zhao Jing Su Xing Liu Tongjuan Zou Wanhong Yin Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study Frontiers in Medicine sepsis autoimmune diseases Mendelian randomization 28-day mortality risk factor |
| title | Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study |
| title_full | Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study |
| title_fullStr | Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study |
| title_full_unstemmed | Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study |
| title_short | Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study |
| title_sort | genetic associations between autoimmune diseases and the risks of severe sepsis and 28 day mortality a two sample mendelian randomization study |
| topic | sepsis autoimmune diseases Mendelian randomization 28-day mortality risk factor |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1331950/full |
| work_keys_str_mv | AT xintie geneticassociationsbetweenautoimmunediseasesandtherisksofseveresepsisand28daymortalityatwosamplemendelianrandomizationstudy AT yanjiezhao geneticassociationsbetweenautoimmunediseasesandtherisksofseveresepsisand28daymortalityatwosamplemendelianrandomizationstudy AT jingsu geneticassociationsbetweenautoimmunediseasesandtherisksofseveresepsisand28daymortalityatwosamplemendelianrandomizationstudy AT xingliu geneticassociationsbetweenautoimmunediseasesandtherisksofseveresepsisand28daymortalityatwosamplemendelianrandomizationstudy AT tongjuanzou geneticassociationsbetweenautoimmunediseasesandtherisksofseveresepsisand28daymortalityatwosamplemendelianrandomizationstudy AT wanhongyin geneticassociationsbetweenautoimmunediseasesandtherisksofseveresepsisand28daymortalityatwosamplemendelianrandomizationstudy |