Exploring the Causality Between Body Mass Index and Sepsis: A Two-Sample Mendelian Randomization Study

Juntao Wang; Yanlan Hu; Jun Zeng; Quan Li; Lanfen He; Wenjie Hao; Xingyue Song; Shijiao Yan; Chuanzhu Lv

doi:10.3389/ijph.2023.1605548

Exploring the Causality Between Body Mass Index and Sepsis: A Two-Sample Mendelian Randomization Study

Int J Public Health. 2023 May 2:68:1605548. doi: 10.3389/ijph.2023.1605548. eCollection 2023.

Authors

Juntao Wang¹, Yanlan Hu¹, Jun Zeng², Quan Li³, Lanfen He¹, Wenjie Hao¹, Xingyue Song^{4

5}, Shijiao Yan^{1

4}, Chuanzhu Lv^{2

4

6}

Affiliations

¹ International School of Public Health and One Health, Hainan Medical University, Haikou, Hainan, China.
² Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
⁴ Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou, China.
⁵ Department of Emergency, Hainan Clinical Research Center for Acute and Critical Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
⁶ Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou, China.

Abstract

Objective: Observational epidemiological studies have shown a link between obesity and sepsis, but any causal relationship is not clear. Our study aimed to explore the correlation and causal relationship between body mass index and sepsis by a two-sample Mendelian randomization (MR). Methods: In large sample genome-wide association studies, single-nucleotide polymorphisms related to body mass index were screened as instrumental variables. Three MR methods, MR-Egger regression, weighted median estimator, and inverse variance-weighted, were used to evaluate the causal relationship between body mass index and sepsis. Odds ratio (OR) and 95% confidence interval (CI) were used as the evaluation index of causality, and sensitivity analyses were conducted to assess pleiotropy and instrument validity. Results: By two-sample MR, the inverse variance weighting method results suggested that increased body mass index was associated with an increased risk of sepsis (odds ratio 1.32; 95% CI 1.21-1.44; p = 1.37 × 10^-9) and streptococcal septicemia (OR 1.46; 95% CI 1.11-1.91; p = 0.007), but there was no causal relationship with puerperal sepsis (OR, 1.06; 95% CI, 0.87-1.28; p = 0.577). Sensitivity analysis was consistent with the results, and there was no heterogeneity and level of pleiotropy. Conclusion: Our study supports a causal relationship between body mass index and sepsis. Proper control of body mass index may prevent sepsis.

Keywords: Mendelian randomization; body mass index; instrumental variable; obesity; sepsis.

MeSH terms

Body Mass Index
Causality
Genome-Wide Association Study*
Humans
Mendelian Randomization Analysis / methods
Sepsis* / epidemiology
Sepsis* / genetics

Grants and funding

This study was supported by Hainan Province Science and Technology Special Fund (ZDKJ202004, ZDKJ2021038), Hainan Provincial Natural Science Foundation of China (821RC557, 2019RC232), National Natural Science Foundation of China (81871611, 82160647), Finance Science and Technology Program of Sichuan Province (2022YFS0602).