Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk
Abstract Introduction Despite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian rand...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-06-01
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| Series: | Infectious Diseases and Therapy |
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| Online Access: | https://doi.org/10.1007/s40121-023-00831-z |
| _version_ | 1797752603217494016 |
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| author | Peipei Lei Weiwei Xu Congjie Wang Guoshuai Lin Songmei Yu Yanli Guo |
| author_facet | Peipei Lei Weiwei Xu Congjie Wang Guoshuai Lin Songmei Yu Yanli Guo |
| author_sort | Peipei Lei |
| collection | DOAJ |
| description | Abstract Introduction Despite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk. Methods We conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane’s Q test and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. Results The IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845–0.987, P = 0.023] and DHA (OR 0.893, 95% CI 0.815–0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95% CI 0.681–0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95% CI 1.011–1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. Conclusion Our study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms. |
| first_indexed | 2024-03-12T17:06:49Z |
| format | Article |
| id | doaj.art-211f8274cadd434a83b4115a07901a83 |
| institution | Directory Open Access Journal |
| issn | 2193-8229 2193-6382 |
| language | English |
| last_indexed | 2024-03-12T17:06:49Z |
| publishDate | 2023-06-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Infectious Diseases and Therapy |
| spelling | doaj.art-211f8274cadd434a83b4115a07901a832023-08-06T11:21:07ZengAdis, Springer HealthcareInfectious Diseases and Therapy2193-82292193-63822023-06-011271797180810.1007/s40121-023-00831-zMendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality RiskPeipei Lei0Weiwei Xu1Congjie Wang2Guoshuai Lin3Songmei Yu4Yanli Guo5Department of Endocrinology, Yantai Yuhuangding HospitalDepartment of Anesthesia, Yantai Yuhuangding HospitalDepartment of Respiratory and Critical Care Medicine, Yantai Yuhuangding HospitalDepartment of Infectious Disease, Yantai Yuhuangding HospitalDepartment of Critical Care Medicine, Yantai Yuhuangding HospitalDepartment of Emergency, Yantai Yuhuangding HospitalAbstract Introduction Despite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk. Methods We conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane’s Q test and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. Results The IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845–0.987, P = 0.023] and DHA (OR 0.893, 95% CI 0.815–0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95% CI 0.681–0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95% CI 1.011–1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. Conclusion Our study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms.https://doi.org/10.1007/s40121-023-00831-zPolyunsaturated fatty acidsSepsisMortalityCausal relationshipMendelian randomization |
| spellingShingle | Peipei Lei Weiwei Xu Congjie Wang Guoshuai Lin Songmei Yu Yanli Guo Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk Infectious Diseases and Therapy Polyunsaturated fatty acids Sepsis Mortality Causal relationship Mendelian randomization |
| title | Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk |
| title_full | Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk |
| title_fullStr | Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk |
| title_full_unstemmed | Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk |
| title_short | Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk |
| title_sort | mendelian randomization analysis reveals causal associations of polyunsaturated fatty acids with sepsis and mortality risk |
| topic | Polyunsaturated fatty acids Sepsis Mortality Causal relationship Mendelian randomization |
| url | https://doi.org/10.1007/s40121-023-00831-z |
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