Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization study
Abstract Infections are serious postoperative complications, and strongly affects the mortality and prognosis of patients. Body mass index (BMI) and lipids are factors in postoperative infection, but a causal relationship has not been know. In this Mendelian randomization (MR) study, we utilized gen...
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2025-04-01
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| author | Tao Yang Zhe Chen Daiyin Cao Wenliang Song Jinlong Jiang Xiaoxun Ma Zhi Mao Xiangdong Guan Jianfeng Wu Rui Shi Xiang Si |
| author_facet | Tao Yang Zhe Chen Daiyin Cao Wenliang Song Jinlong Jiang Xiaoxun Ma Zhi Mao Xiangdong Guan Jianfeng Wu Rui Shi Xiang Si |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | Abstract Infections are serious postoperative complications, and strongly affects the mortality and prognosis of patients. Body mass index (BMI) and lipids are factors in postoperative infection, but a causal relationship has not been know. In this Mendelian randomization (MR) study, we utilized genome-wide association study (GWAS) data from the Global Lipids Genetics Consortium and FinnGen database, treating lipids and BMI as exposures. Postoperative infection GWAS data from the UK Biobank served as the outcome. We utilized linkage disequilibrium score regression (LDSC) analysis to evaluate the genetic correlations between lipids, BMI, and postoperative infections. We employed univariate and reverse MR analyses to explore the causal relationships between exposure and outcome factors. The analysis primarily utilized the inverse variance weighted method, supplemented by MR-Egger and weighted median methods. The MR-PRESSO method was used to detect horizontal pleiotropy and potential outliers. Additionally, stepwise mediation MR analysis was employed to investigate indirect factors potentially influencing the relationships between lipids, BMI, and postoperative infections. The genetic covariance analysis indicates that there is no sample overlap among all the GWAS conducted. In the LDSC analysis, genetic correlations (GC) were found between BMI(GC = 0.430, P < 0.05), HDL-C(GC = − 0.414, P < 0.05), nonHDL-C(GC = 0.137, P < 0.05), TG(GC = 0.417, P < 0.05), and postoperative infection. HDL-C showing a negative genetic association with postoperative infection, while other phenotypes showed positive associations. In MR analysis, causal relationships were identified between BMI and postoperative infection (OR = 1.36, 95% CI = 1.16–1.60, P < 0.05) and HDL-C and postoperative infection (OR = 0.87, 95% CI = 0.78–0.96, P < 0.05), with BMI showing a positive causal association and HDL-C showing a negative causal association with postoperative infection. These findings are consistent with the LDSC results. In the reverse MR analysis, there was no significant causal relationship identified between postoperative infection and both BMI and lipids. Stepwise mediation MR analysis excluded the impact of potential mediating factors between exposure and outcomes. In this study, through LDSC and MR analyses, we identified genetic correlations and causal links between BMI, HDL, and postoperative infection. It was found that BMI might increase the risk of postoperative infection, whereas HDL could potentially lower the risk of developing postoperative infection. |
| format | Article |
| id | doaj-art-763edbcb881242e3bde5a815ab12a77d |
| institution | OA Journals |
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| spelling | doaj-art-763edbcb881242e3bde5a815ab12a77d2025-08-20T02:17:05ZengNature PortfolioScientific Reports2045-23222025-04-0115111010.1038/s41598-025-95812-2Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization studyTao Yang0Zhe Chen1Daiyin Cao2Wenliang Song3Jinlong Jiang4Xiaoxun Ma5Zhi Mao6Xiangdong Guan7Jianfeng Wu8Rui Shi9Xiang Si10Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Thoracic Surgery, The Second Xiangya Hospital, Central South UniversityDepartment of Critical Care Medicine, The Sixth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Critical Care Medicine, The First Medical Centre, Chinese PLA General HospitalDepartment of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen UniversityAbstract Infections are serious postoperative complications, and strongly affects the mortality and prognosis of patients. Body mass index (BMI) and lipids are factors in postoperative infection, but a causal relationship has not been know. In this Mendelian randomization (MR) study, we utilized genome-wide association study (GWAS) data from the Global Lipids Genetics Consortium and FinnGen database, treating lipids and BMI as exposures. Postoperative infection GWAS data from the UK Biobank served as the outcome. We utilized linkage disequilibrium score regression (LDSC) analysis to evaluate the genetic correlations between lipids, BMI, and postoperative infections. We employed univariate and reverse MR analyses to explore the causal relationships between exposure and outcome factors. The analysis primarily utilized the inverse variance weighted method, supplemented by MR-Egger and weighted median methods. The MR-PRESSO method was used to detect horizontal pleiotropy and potential outliers. Additionally, stepwise mediation MR analysis was employed to investigate indirect factors potentially influencing the relationships between lipids, BMI, and postoperative infections. The genetic covariance analysis indicates that there is no sample overlap among all the GWAS conducted. In the LDSC analysis, genetic correlations (GC) were found between BMI(GC = 0.430, P < 0.05), HDL-C(GC = − 0.414, P < 0.05), nonHDL-C(GC = 0.137, P < 0.05), TG(GC = 0.417, P < 0.05), and postoperative infection. HDL-C showing a negative genetic association with postoperative infection, while other phenotypes showed positive associations. In MR analysis, causal relationships were identified between BMI and postoperative infection (OR = 1.36, 95% CI = 1.16–1.60, P < 0.05) and HDL-C and postoperative infection (OR = 0.87, 95% CI = 0.78–0.96, P < 0.05), with BMI showing a positive causal association and HDL-C showing a negative causal association with postoperative infection. These findings are consistent with the LDSC results. In the reverse MR analysis, there was no significant causal relationship identified between postoperative infection and both BMI and lipids. Stepwise mediation MR analysis excluded the impact of potential mediating factors between exposure and outcomes. In this study, through LDSC and MR analyses, we identified genetic correlations and causal links between BMI, HDL, and postoperative infection. It was found that BMI might increase the risk of postoperative infection, whereas HDL could potentially lower the risk of developing postoperative infection.https://doi.org/10.1038/s41598-025-95812-2High density lipoproteinBody mass indexPostoperative infectionLinkage disequilibrium score regressionMendelian randomization |
| spellingShingle | Tao Yang Zhe Chen Daiyin Cao Wenliang Song Jinlong Jiang Xiaoxun Ma Zhi Mao Xiangdong Guan Jianfeng Wu Rui Shi Xiang Si Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization study Scientific Reports High density lipoprotein Body mass index Postoperative infection Linkage disequilibrium score regression Mendelian randomization |
| title | Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization study |
| title_full | Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization study |
| title_fullStr | Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization study |
| title_full_unstemmed | Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization study |
| title_short | Genetic correlations and causal associations between BMI, HDL-C, and postoperative infections: a two-sample Mendelian randomization study |
| title_sort | genetic correlations and causal associations between bmi hdl c and postoperative infections a two sample mendelian randomization study |
| topic | High density lipoprotein Body mass index Postoperative infection Linkage disequilibrium score regression Mendelian randomization |
| url | https://doi.org/10.1038/s41598-025-95812-2 |
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