Causal relationship between increased waist circumference and sepsis based on bidirectional two-sample Mendelian randomization analysis

LIU Tingting; SUN Zhiling; XIAO Qiao; WEN Jiamin; MA Jiatian; QIU Ying

doi:10.16766/j.cnki.issn.1674-4152.004359

Volume 24 Issue 2

Feb. 2026

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Article Navigation > Chinese Journal of General Practice > 2026 > 24(2): 196-199

LIU Tingting, SUN Zhiling, XIAO Qiao, WEN Jiamin, MA Jiatian, QIU Ying. Causal relationship between increased waist circumference and sepsis based on bidirectional two-sample Mendelian randomization analysis[J]. Chinese Journal of General Practice, 2026, 24(2): 196-199. doi: 10.16766/j.cnki.issn.1674-4152.004359

Citation:

LIU Tingting, SUN Zhiling, XIAO Qiao, WEN Jiamin, MA Jiatian, QIU Ying. Causal relationship between increased waist circumference and sepsis based on bidirectional two-sample Mendelian randomization analysis[J]. Chinese Journal of General Practice, 2026, 24(2): 196-199. doi: 10.16766/j.cnki.issn.1674-4152.004359

Citation:

LIU Tingting, SUN Zhiling, XIAO Qiao, WEN Jiamin, MA Jiatian, QIU Ying. Causal relationship between increased waist circumference and sepsis based on bidirectional two-sample Mendelian randomization analysis[J]. Chinese Journal of General Practice, 2026, 24(2): 196-199. doi: 10.16766/j.cnki.issn.1674-4152.004359

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Causal relationship between increased waist circumference and sepsis based on bidirectional two-sample Mendelian randomization analysis

doi: 10.16766/j.cnki.issn.1674-4152.004359

LIU Tingting^{1, 2}
, SUN Zhiling^{2
,
,}
, XIAO Qiao^{2, 3}
, WEN Jiamin²
, MA Jiatian²
, QIU Ying²

1.
Department of ICU, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China

Funds:

MS2023012

Received Date: 2025-03-29
Available Online: 2026-04-11

Abstract

Abstract

Objective To explore the potential causal relationship between waist circumference and sepsis using a two-sample Mendelian randomization (MR) analysis, providing evidence-based support for the clinical identification of high-risk individuals with central obesity and the development of prevention and intervention strategies for infectious diseases. Methods This study used a two-sample bidirectional Mendelian randomization design. The waist circumference served as the exposure variable (n=462 166), and sepsis was the outcome (11 643 cases and 474 841 controls). Data are sourced from the genome-wide association studies (GWAS) dataset. Single nucleotide polymorphisms (SNPs) associated with waist circumference (P < 5×10^-8) and independent of linkage disequilibrium (distance>10 000 kb, r² < 0.001) were selected as instrumental variables. The inverse variance weighting (IVW) method was used as the primary analytical approach, supplemented with MR-Egger regression, weighted median, simple model, and weighted model analyses. Horizontal pleiotropy was assessed through MR-Egger intercept tests, and sensitivity analysis was conducted using the "leave-one-out" method to ensure the stability and reliability of the results. Results MR analysis showed a significant positive causal relationship between waist circumference and sepsis risk in genetic prediction. The IVW analysis revealed that each standard deviation increase in waist circumference was associated with a 75.3% higher risk of sepsis (OR=1.753, 95% CI: 1.571-1.956, P < 0.001), with consistent results across multiple MR methods. Sensitivity analysis and pleiotropy tests indicated robustness of the findings, with no significant bias. Gender-stratified analysis showed consistent associations between waist circumference and sepsis risk in both men and women. Reverse MR analysis did not identify a significant effect of sepsis on waist circumference. Conclusion This study supports the hypothesis that increased waist circumference may be an independent risk factor for sepsis. These findings underscore the importance of recognizing central obesity as a high-risk condition in populations susceptible to infectious diseases and offer new genetic evidence for the prevention and management of sepsis.
- Sepsis,
- Waist circumference,
- Mendelian randomization,
- Genetic prediction,
- Causal relationship

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References(25)

References

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Causal relationship between increased waist circumference and sepsis based on bidirectional two-sample Mendelian randomization analysis

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