基于双向两样本孟德尔随机化分析腰围增粗与脓毒症的因果关系

刘婷婷; 孙志岭; 肖俏; 文嘉旻; 马佳田; 仇营

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

基于双向两样本孟德尔随机化分析腰围增粗与脓毒症的因果关系

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

刘婷婷^{1, 2},
孙志岭^2, ,,
肖俏^{2, 3},
文嘉旻²,
马佳田²,
仇营²

1.
南京中医药大学附属医院重症医学科，江苏南京 210029
2.
南京中医药大学护理学院，江苏南京 210023
3.
南京中医药大学附属医院心内科

基金项目:

江苏省中医药科技发展计划项目 MS2023012

详细信息

通讯作者:
孙志岭，E-mail：szl@njucm.edu.cn

中图分类号: R631
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出版历程
- 收稿日期: 2025-03-29
- 网络出版日期: 2026-04-11

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

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

摘要

摘要: 目的使用两样本孟德尔随机化分析，探讨腰围与脓毒症之间的潜在因果关系，为临床精准识别中心性肥胖人群中的高风险个体、制定感染性疾病的预防与干预策略提供循证依据。方法本研究为两样本双向MR设计，暴露变量为腰围(样本量462 166例)，结局变量为脓毒症(病例11 643例，对照474 841例)，数据均来源于全基因组关联研究(GWAS)数据集，以P＜5×10^-8、SNP间距离＞10 000 kb、r²＜0.001为筛选标准，选取腰围相关的单核苷酸多态性(SNP)作为工具变量。主分析方法为逆方差加权法(IVW)，辅以MR-Egger回归、加权中位数法、简单模型及加权模型。通过MR-Egger截距检验评估水平多效性，采用“留一法”进行敏感性分析，确保结果的稳定性和可靠性。结果 MR分析显示腰围与脓毒症在遗传预测上存在显著正向因果关系，IVW分析显示腰围每增加1个标准差，脓毒症的发生风险增加0.753倍(OR=1.753，95% CI：1.571~1.956，P＜0.001)，多种方法分析结果一致。敏感性分析及多效性检验提示结果稳健，未发现明显的偏倚。性别分层分析显示，男性和女性腰围与脓毒症风险关系一致。反向MR分析未发现脓毒症对腰围存在显著影响。结论本研究结果显示腰围增粗可增加脓毒症的发生风险，提示临床上应关注中心性肥胖人群在感染性疾病中的高风险价值，这为脓毒症的预防和管理提供了遗传学层面的新证据。
- 脓毒症 /
- 腰围 /
- 孟德尔随机化 /
- 遗传预测 /
- 因果关系
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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图 1 腰围与脓毒症的MR分析散点图

Figure 1. Scatter plot of MR analysis of waist circumference and sepsis

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表 1 腰围与脓毒症相关数据信息

Table 1. GWAS summary information on waist circumference and sepsis

数据	人群	病例	对照	总样本量	SNP数量	来源	年份
腰围	European	NA	NA	462 166	9 851 867	ukb-b-9405	2018
腰围(男性)	European	NA	NA	104 079	2 294 966	ieu-a-71	2015
腰围(女性)	European	NA	NA	127 469	2 473 036	ieu-a-69	2015
脓毒症	European	11 643	474 841	486 484	12 243 539	ieu-b-4980	2021
注：NA表示未提供。

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表 2 腰围与脓毒症之间因果关系的MR分析

Table 2. MR analysis of the causal relationship between waist circumference and sepsis

暴露因素	结局因素	MR分析方法	OR值	95% CI	P值	F值
腰围	脓毒症	IVW	1.753	1.571~1.956	＜0.001	29.794~997.383
		MR-Egger回归法	1.374	1.004~1.880	0.047
		WM	1.689	1.382~2.065	＜0.001
		简单模型	1.928	1.148~2.550	0.013
		加权模型	1.759	1.214~2.550	0.003
腰围(男性)	脓毒症	IVW	1.031	0.874~1.215	0.719	29.961~86.224
		MR-Egger回归法	1.286	0.522~3.166	0.589
		WM	1.032	0.819~1.299	0.787
		简单模型	0.870	0.552~1.373	0.555
		加权模型	1.027	0.688~1.534	0.897
腰围(女性)	脓毒症	IVW	1.107	0.923~1.328	0.272	30.362~130.612
		MR-Egger回归法	0.967	0.466~2.004	0.929
		WM	1.132	0.869~1.474	0.358
		简单模型	1.183	0.742~1.889	0.488
		加权模型	1.099	0.737~1.638	0.648
脓毒症	腰围	IVW	1.017	0.999~1.035	0.065	20.914~25.472
		MR-Egger回归法	1.024	0.987~1.061	0.210
		WM	1.017	0.995~1.040	0.125
		简单模型	1.025	0.986~1.066	0.229
		加权模型	1.021	0.984~1.060	0.284

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