Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study
Abstract Background Educational attainment is inversely related to sepsis risk, but the causal nature is still unclear. We therefore conducted the first Mendelian randomization (MR) study of genetically predicted educational attainment on sepsis that also uses a within-family genetic instrument for...
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2025-05-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-025-11130-y |
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| author | Vilde Hatlevoll Stensrud Tormod Rogne Helene Marie Flatby Randi Marie Mohus Lise Tuset Gustad Tom Ivar Lund Nilsen |
| author_facet | Vilde Hatlevoll Stensrud Tormod Rogne Helene Marie Flatby Randi Marie Mohus Lise Tuset Gustad Tom Ivar Lund Nilsen |
| author_sort | Vilde Hatlevoll Stensrud |
| collection | DOAJ |
| description | Abstract Background Educational attainment is inversely related to sepsis risk, but the causal nature is still unclear. We therefore conducted the first Mendelian randomization (MR) study of genetically predicted educational attainment on sepsis that also uses a within-family genetic instrument for education. To further explore possible mechanistic pathways that can inform strategies to reduce sepsis risk, we examined the mediating effects of factors that are modifiable or can be prevented. Methods The association between genetically predicted educational attainment and sepsis was estimated using summary-level data from recent genome-wide association studies. Possible bias due to population stratification, dynastic effects, and assortative mating in the genetic instrument for education was evaluated using summary-level data from a within-sibship genome-wide association study. We used inverse variance weighted MR analysis to estimate the effect of one standard deviation increase in years of education on sepsis risk. The robustness of the findings was assessed in sensitivity analyses, applying weighted median, weighted mode, and MR Egger regression. Finally, we applied multivariable MR analyses to estimate the mediating effects of smoking initiation, alcohol consumption, body mass index, high-density lipoprotein (HDL)-cholesterol, systolic blood pressure and type 2 diabetes. Results For each standard deviation increase in genetically predicted educational attainment (3.4 years), the odds ratio (OR) for sepsis was 0.72 (95% confidence interval (CI) 0.66 to 0.78). The results of the analysis using the within-sibship genetic instrument and other sensitivity analyses were in line with this finding: within-sibship OR 0.88 (95% CI 0.64 to 1.18), weighted median OR 0.70 (95% CI 0.62 to 0.80), weighted mode OR 0.70 (95% CI 0.43 to 1.13), and MR Egger OR 0.65 (95% CI 0.50 to 0.85). The mediation analysis showed that 56% of the effect of educational attainment on sepsis risk can be explained by modifiable or preventable factors. Conclusions Higher educational attainment is strongly associated with a reduced risk of sepsis, pointing to important socioeconomic differences in this disease. The results also suggest that interventions targeting modifiable or preventable factors could contribute to reducing the socioeconomic differences in sepsis risk. |
| format | Article |
| id | doaj-art-7ab644f8e56a4eddbbb96ccd87ae525a |
| institution | Kabale University |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Infectious Diseases |
| spelling | doaj-art-7ab644f8e56a4eddbbb96ccd87ae525a2025-08-20T03:48:18ZengBMCBMC Infectious Diseases1471-23342025-05-0125111010.1186/s12879-025-11130-yExamining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization studyVilde Hatlevoll Stensrud0Tormod Rogne1Helene Marie Flatby2Randi Marie Mohus3Lise Tuset Gustad4Tom Ivar Lund Nilsen5Department of Public Health and Nursing, Norwegian University of Science and TechnologyDepartment of Community Medicine and Global Health, University of OsloMid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and TechnologyMid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and TechnologyFaculty of Nursing and Health Sciences, Nord UniversityDepartment of Public Health and Nursing, Norwegian University of Science and TechnologyAbstract Background Educational attainment is inversely related to sepsis risk, but the causal nature is still unclear. We therefore conducted the first Mendelian randomization (MR) study of genetically predicted educational attainment on sepsis that also uses a within-family genetic instrument for education. To further explore possible mechanistic pathways that can inform strategies to reduce sepsis risk, we examined the mediating effects of factors that are modifiable or can be prevented. Methods The association between genetically predicted educational attainment and sepsis was estimated using summary-level data from recent genome-wide association studies. Possible bias due to population stratification, dynastic effects, and assortative mating in the genetic instrument for education was evaluated using summary-level data from a within-sibship genome-wide association study. We used inverse variance weighted MR analysis to estimate the effect of one standard deviation increase in years of education on sepsis risk. The robustness of the findings was assessed in sensitivity analyses, applying weighted median, weighted mode, and MR Egger regression. Finally, we applied multivariable MR analyses to estimate the mediating effects of smoking initiation, alcohol consumption, body mass index, high-density lipoprotein (HDL)-cholesterol, systolic blood pressure and type 2 diabetes. Results For each standard deviation increase in genetically predicted educational attainment (3.4 years), the odds ratio (OR) for sepsis was 0.72 (95% confidence interval (CI) 0.66 to 0.78). The results of the analysis using the within-sibship genetic instrument and other sensitivity analyses were in line with this finding: within-sibship OR 0.88 (95% CI 0.64 to 1.18), weighted median OR 0.70 (95% CI 0.62 to 0.80), weighted mode OR 0.70 (95% CI 0.43 to 1.13), and MR Egger OR 0.65 (95% CI 0.50 to 0.85). The mediation analysis showed that 56% of the effect of educational attainment on sepsis risk can be explained by modifiable or preventable factors. Conclusions Higher educational attainment is strongly associated with a reduced risk of sepsis, pointing to important socioeconomic differences in this disease. The results also suggest that interventions targeting modifiable or preventable factors could contribute to reducing the socioeconomic differences in sepsis risk.https://doi.org/10.1186/s12879-025-11130-yEducationSocioeconomic statusSepsisMendelian randomizationMediation analysisHealth inequalities |
| spellingShingle | Vilde Hatlevoll Stensrud Tormod Rogne Helene Marie Flatby Randi Marie Mohus Lise Tuset Gustad Tom Ivar Lund Nilsen Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study BMC Infectious Diseases Education Socioeconomic status Sepsis Mendelian randomization Mediation analysis Health inequalities |
| title | Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study |
| title_full | Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study |
| title_fullStr | Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study |
| title_full_unstemmed | Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study |
| title_short | Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study |
| title_sort | examining socioeconomic differences in sepsis risk and mediation by modifiable factors a mendelian randomization study |
| topic | Education Socioeconomic status Sepsis Mendelian randomization Mediation analysis Health inequalities |
| url | https://doi.org/10.1186/s12879-025-11130-y |
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