The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis
Abstract Objective The causal associations of circulating lipids with Barrett’s Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. Methods We conducted two-sample Mendelian randomiza...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-024-00608-6 |
| _version_ | 1797199352091901952 |
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| author | Baofeng Li Meng Li Xiao Qi Ti Tong Guangxin zhang |
| author_facet | Baofeng Li Meng Li Xiao Qi Ti Tong Guangxin zhang |
| author_sort | Baofeng Li |
| collection | DOAJ |
| description | Abstract Objective The causal associations of circulating lipids with Barrett’s Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. Methods We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 − 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran’s Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. Results None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). Conclusion This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future. |
| first_indexed | 2024-04-24T07:14:23Z |
| format | Article |
| id | doaj.art-afada97c648343a5ae441019b2f8bc3a |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-24T07:14:23Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-afada97c648343a5ae441019b2f8bc3a2024-04-21T11:24:49ZengBMCHuman Genomics1479-73642024-04-011811710.1186/s40246-024-00608-6The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysisBaofeng Li0Meng Li1Xiao Qi2Ti Tong3Guangxin zhang4Department of Thoracic Surgery, The Second Hospital of Jilin UniversityDepartment of Thoracic Surgery, The Second Hospital of Jilin UniversityDepartment of Thoracic Surgery, The Second Hospital of Jilin UniversityDepartment of Thoracic Surgery, The Second Hospital of Jilin UniversityDepartment of Thoracic Surgery, The Second Hospital of Jilin UniversityAbstract Objective The causal associations of circulating lipids with Barrett’s Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. Methods We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 − 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran’s Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. Results None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). Conclusion This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future.https://doi.org/10.1186/s40246-024-00608-6Barrett's EsophagusEsophageal CancerMendelian randomizationCirculating lipidTriglycerides |
| spellingShingle | Baofeng Li Meng Li Xiao Qi Ti Tong Guangxin zhang The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis Human Genomics Barrett's Esophagus Esophageal Cancer Mendelian randomization Circulating lipid Triglycerides |
| title | The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis |
| title_full | The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis |
| title_fullStr | The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis |
| title_full_unstemmed | The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis |
| title_short | The causal associations of circulating lipids with Barrett’s Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis |
| title_sort | causal associations of circulating lipids with barrett s esophagus and esophageal cancer a bi directional two sample mendelian randomization analysis |
| topic | Barrett's Esophagus Esophageal Cancer Mendelian randomization Circulating lipid Triglycerides |
| url | https://doi.org/10.1186/s40246-024-00608-6 |
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