Dataset Information

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

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.

SUBMITTER: Wang J

PROVIDER: S-EPMC10186272 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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

Wang Juntao J Hu Yanlan Y Zeng Jun J Li Quan Q He Lanfen L Hao Wenjie W Song Xingyue X Yan Shijiao S Lv Chuanzhu C

International journal of public health 20230502

<b>Objective:</b> 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). <b>Methods:</b> 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, weig ...[more]

PMID: 37205044

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Project description:Background: Observational evidence has shown that smoking, alcohol consumption, type 2 diabetes, and body mass index (BMI) are risk factors for peptic ulcer disease (PUD), including gastric ulcer (GU) and duodenal ulcer (DU). However, the observed associations may be confounding factors. Herein, we use Mendelian randomization (MR) to examine causal associations such as smoking, alcohol, type 2 diabetes, BMI, and risks of PUD. Methods: We used 8,17,41,325,82, 231, and 616 identified genetic variants as proxies for age of smoking initiation (AgeSmk), smoking cessation (SmkCes, current/former), number of cigarettes smoked per day (CigDay), smoking status (SmkIni, ever/never), alcohol consumption, type 2 diabetes, and BMI to obtain unconfounded effect estimates on the GU and DU levels among 452,264 participants from the Gene ATLAS. The causal relationship was estimated by using inverse-variance weighted (IVW) as the main method. Sensitivity analysis includes Cochran's Q test, the MR-Egger test, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS). In addition, secondary MR analysis was conducted within summary data using genetic risk scores (GRSs) as instrumental variables (IVs). Results: In our two-sample MR analyses, genetic predisposition to smoking (SmkInit) and BMI were associated with an increased risk of GU. The beta values were 0.0035 (95% CI, 0.0021, 0.0049, p = 1.56E-06) for smoking (SmkInit) and 0.0021 (95% CI, 0.0009, 0.0033, p = 0.0008) for BMI. Genetic predisposition to smoking (SmkInit) and higher genetically predicted BMI were associated with an increased risk of DU. The beta values of DU were 0.0029 (95% CI, 0.0017, 0.0041, p = 2.43E-06) for smoking (SmkInit) and 0.0018 (95% CI, 0.0007, 0.0029, p = 0.001) for BMI. No other causal association between smoking (AgeSmk, CigDay, and SmkCes), alcohol consumption, type 2 diabetes, and GU or DU was observed. Consistent results were obtained in sensitivity analyses. Furthermore, the GRS approach showed similar results in the several MR methods. Conclusion: These findings do not support a causal role of AgeSmk, CigDay, SmkCes, alcohol consumption, and type 2 diabetes in the development of GU and DU. However, it is confirmed that SmkInit and BMI have a causal part in the development of GU and DU.

Project description:IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Dataset Information

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

Publications

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

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