Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study
Background and Aim: Previous observational studies indicated that the serum albumin levels and circulating metabolites are associated with a high risk of venous thromboembolism (VTE). However, whether these observations reflect causality remained unclear. Hence, we conducted a two-sample Mendelian r...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2021.712600/full |
| _version_ | 1818990159716155392 |
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| author | Zhengye Liu Jiarui Mi |
| author_facet | Zhengye Liu Jiarui Mi |
| author_sort | Zhengye Liu |
| collection | DOAJ |
| description | Background and Aim: Previous observational studies indicated that the serum albumin levels and circulating metabolites are associated with a high risk of venous thromboembolism (VTE). However, whether these observations reflect causality remained unclear. Hence, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal associations of serum albumin and circulating metabolites with the risk of VTE.Methods and Results: Summary statistics of genetic instruments proxying serum albumin, total protein, and common circulating metabolites were extracted from genome-wide association studies in the European ancestry. Summary-level results of age- and sex-adjusted estimates for associations of the instruments with VTE were derived from the FinnGen consortium. We used the inverse-variance weighted (IVW) method as the primary analysis for univariable MR. Sensitivity analyses were performed to detect horizontal pleiotropy and outliers. Genetically proxied high-serum albumin and total protein levels were suggestive protective factor of VTE, with odds ratio (OR) = 0.69 (CI 0.54–0.89, p = 4.7 × 10−3) and 0.76 (CI 0.61–0.95, p = 0.015), respectively. Genetically proxied low-monounsaturated fatty acids and the ratio of monounsaturated fatty acid to total fatty acid are causally associated with increased risk of VTE, with ORs = 0.89 (CI 0.80–0.99, p = 0.031) and 0.85 (CI 0.78–0.94, p = 9.92 × 10−4), respectively. There is no indication of causal associations between other circulating metabolites and the risk of VTE.Conclusions: Genetically liability to low-serum albumin and total protein levels, low proxied monounsaturated fatty acids (MUFAs) and the ratio of MUFAs to total fatty acids are associated with the higher risk of VTE. |
| first_indexed | 2024-12-20T19:49:57Z |
| format | Article |
| id | doaj.art-931233e737b54e5daec1cb4404f708fb |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-12-20T19:49:57Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-931233e737b54e5daec1cb4404f708fb2022-12-21T19:28:20ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2021-11-01810.3389/fnut.2021.712600712600Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization StudyZhengye Liu0Jiarui Mi1Second School of Clinical Medicine, Zhongnan Hospital of Wuhan University, Wuhan, ChinaState Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackground and Aim: Previous observational studies indicated that the serum albumin levels and circulating metabolites are associated with a high risk of venous thromboembolism (VTE). However, whether these observations reflect causality remained unclear. Hence, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal associations of serum albumin and circulating metabolites with the risk of VTE.Methods and Results: Summary statistics of genetic instruments proxying serum albumin, total protein, and common circulating metabolites were extracted from genome-wide association studies in the European ancestry. Summary-level results of age- and sex-adjusted estimates for associations of the instruments with VTE were derived from the FinnGen consortium. We used the inverse-variance weighted (IVW) method as the primary analysis for univariable MR. Sensitivity analyses were performed to detect horizontal pleiotropy and outliers. Genetically proxied high-serum albumin and total protein levels were suggestive protective factor of VTE, with odds ratio (OR) = 0.69 (CI 0.54–0.89, p = 4.7 × 10−3) and 0.76 (CI 0.61–0.95, p = 0.015), respectively. Genetically proxied low-monounsaturated fatty acids and the ratio of monounsaturated fatty acid to total fatty acid are causally associated with increased risk of VTE, with ORs = 0.89 (CI 0.80–0.99, p = 0.031) and 0.85 (CI 0.78–0.94, p = 9.92 × 10−4), respectively. There is no indication of causal associations between other circulating metabolites and the risk of VTE.Conclusions: Genetically liability to low-serum albumin and total protein levels, low proxied monounsaturated fatty acids (MUFAs) and the ratio of MUFAs to total fatty acids are associated with the higher risk of VTE.https://www.frontiersin.org/articles/10.3389/fnut.2021.712600/fullmendelian randomization analysisvenous thromboembolismserum albuminmetabolic syndromemonounsaturated fatty acid |
| spellingShingle | Zhengye Liu Jiarui Mi Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study Frontiers in Nutrition mendelian randomization analysis venous thromboembolism serum albumin metabolic syndrome monounsaturated fatty acid |
| title | Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study |
| title_full | Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study |
| title_fullStr | Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study |
| title_full_unstemmed | Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study |
| title_short | Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study |
| title_sort | serum albumin and circulating metabolites and risk of venous thromboembolism a two sample mendelian randomization study |
| topic | mendelian randomization analysis venous thromboembolism serum albumin metabolic syndrome monounsaturated fatty acid |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2021.712600/full |
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