Genetic Association of Lipids Characteristics and Lipid Lowering Drug Target Genes with Sepsis
Yu Wang, Haiyue Zhang, Yuanyuan Zhan, Zhuoran Li, Sujing Li, Yingchao Zhang, Shubin Guo.
Abstract
Sepsis is a severe systemic infection that can result in organ dysfunction and mortality. Dyslipidemia emerges as a key player in the intricate web of sepsis pathogenesis. Yet, the causal relationship between blood lipid profiles and sepsis risk remains uncertain. This study aims to investigate the association between genetically predicted lipid traits, drug targets, and sepsis.
Introduction
Sepsis, a major challenge for clinicians, is a deadly syndrome that ensues when the body’s immune system overreacts to an infection. The advent of septic shock and subsequent failure of multiple organs pose a serious risk to the patient’s life, particularly in severe cases. Despite extensive study, sepsis still presents significant obstacles to effective treatment and early identification. To improve patient outcomes, there is still an urgent need to promptly identify risk factors and devise novel therapeutic strategies.
Materials and Methods:
This study followed the Strengthening the Reporting of Observational Studies in Epidemiology-Mendelian Randomisation reporting guidelines. To conduct this investigation, publicly accessible GWAS datasets and eQTL datasets were employed, for which prior informed consent and ethical approval had been acquired. Our study did not need ethical approval given that our investigation used publicly available summary statistics.
Discussion:
In this MR study, we investigated the causal effect of genetically predicted lipid traits on sepsis using univariable MR and multivariable MR approaches. Our findings reveal a protective effect of increasing genetically predicted levels of HDL-C and ApoA-I on the risk of sepsis. Moreover, multivariable MR analysis showed that ApoA-I, ApoB, and LDL-C are causally associated with the risk of sepsis. Notably, we have identified ANGPTL3 and LPL as potential drug targets that significantly lowered the risk of sepsis. Our study provided strong evidence that ANGPTL3 and LPL are promising drug targets for sepsis.
Acknowledgments:
We are grateful to all the studies that have made the public GWAS summary data available, and to all the investigators and participants who contributed to these studies.
Citation: Wang Y, Zhang H, Zhan Y, Li Z, Li S, Zhang Y, et al. (2025) Genetic association of lipids characteristics and lipid lowering drug target genes with sepsis. PLoS One 20(9): e0331023. https://doi.org/10.1371/journal.pone.0331023
Editor: Jérôme Robert, University Hospital Zurich: UniversitatsSpital Zurich, SWITZERLAND
Received: December 12, 2024; Accepted: August 8, 2025; Published: September 11, 2025.
Copyright: © 2025 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The datasets analyzed in this study are publicly available summary statistics. The GWAS Summary statistics used in this study were publicly accessed from the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk/).
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors declare no competing interests.
