Mingfen Sun, Yi Chen, Zhaoquan Jin, Bo Yang, Minghui Zhu
{"title":"Causal association between medication use and sepsis: A two-sample Mendelian randomization study.","authors":"Mingfen Sun, Yi Chen, Zhaoquan Jin, Bo Yang, Minghui Zhu","doi":"10.1097/SHK.0000000000002582","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Objective: This study aimed to explore the causal association between genetically predicted medication use and sepsis.Methods: Utilizing summary data from genome-wide association studies (GWAS) on selected medications use and sepsis, a two-sample Mendelian randomization (MR) design was employed. Analysis was conducted using the Inverse Variance Weighted (IVW), weighted median, weighted mode, and MR-Egger regression methods. Sensitivity analysis included MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out methods.Results: The IVW method suggested that genetically predicted medication use, including Drugs used in diabetes (OR=1.08, 95%CI: 1.02 - 1.15, p=0.015), Diuretics (OR=1.08, 95%CI: 1.01 - 1.15, p=0.034), Thyroid preparations (OR=1.08, 95%CI: 1.03 - 1.13, p=0.001), and Adrenergics (OR=1.09, 95%CI: 1.01 - 1.18, p=0.037), might be causally associated with a higher risk of sepsis. Datasets for drugs in diabetes, antithrombotic agents, renin-angiotensin system agents, anilides, and glucocorticoids may exhibit heterogeneity. MR-Egger regression results indicated minimal influence of horizontal pleiotropy on all associations except possibly for antithrombotic agents and sepsis. MR-PRESSO test found no outliers. Leave-one-out analysis confirmed associations were not driven by any single factor. After removing confounders, the IVW method suggested that genetically predicted diuretics use (OR=1.17, 95%CI: 1.03 - 1.34, p=0.018) might be causally associated with a higher risk of sepsis, while drugs used in diabetes, thyroid preparations, and inhaled adrenergics were not. No heterogeneity was observed. MR-Egger regression results indicated the minimal influence of horizontal pleiotropy on all associations. MR-PRESSO test found no outliers. Leave-one-out analysis confirmed any single factor did not drive associations.Conclusions: This study found that prior use of diuretics may increase sepsis risk, with inconclusive evidence for other medications.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SHOCK","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/SHK.0000000000002582","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: Objective: This study aimed to explore the causal association between genetically predicted medication use and sepsis.Methods: Utilizing summary data from genome-wide association studies (GWAS) on selected medications use and sepsis, a two-sample Mendelian randomization (MR) design was employed. Analysis was conducted using the Inverse Variance Weighted (IVW), weighted median, weighted mode, and MR-Egger regression methods. Sensitivity analysis included MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out methods.Results: The IVW method suggested that genetically predicted medication use, including Drugs used in diabetes (OR=1.08, 95%CI: 1.02 - 1.15, p=0.015), Diuretics (OR=1.08, 95%CI: 1.01 - 1.15, p=0.034), Thyroid preparations (OR=1.08, 95%CI: 1.03 - 1.13, p=0.001), and Adrenergics (OR=1.09, 95%CI: 1.01 - 1.18, p=0.037), might be causally associated with a higher risk of sepsis. Datasets for drugs in diabetes, antithrombotic agents, renin-angiotensin system agents, anilides, and glucocorticoids may exhibit heterogeneity. MR-Egger regression results indicated minimal influence of horizontal pleiotropy on all associations except possibly for antithrombotic agents and sepsis. MR-PRESSO test found no outliers. Leave-one-out analysis confirmed associations were not driven by any single factor. After removing confounders, the IVW method suggested that genetically predicted diuretics use (OR=1.17, 95%CI: 1.03 - 1.34, p=0.018) might be causally associated with a higher risk of sepsis, while drugs used in diabetes, thyroid preparations, and inhaled adrenergics were not. No heterogeneity was observed. MR-Egger regression results indicated the minimal influence of horizontal pleiotropy on all associations. MR-PRESSO test found no outliers. Leave-one-out analysis confirmed any single factor did not drive associations.Conclusions: This study found that prior use of diuretics may increase sepsis risk, with inconclusive evidence for other medications.
期刊介绍：
SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.
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