Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study

Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven...

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Autores principales:	Yuanlong Hu, Xiaomeng Cheng, Huaiyu Mao, Xianhai Chen, Yue Cui, Zhanjun Qiu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	iron status iron metabolism sepsis infection bidirectional mendelian randomization analyses Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/f7a6167b51ac4615a3a8e46fa59da327
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spelling	oai:doaj.org-article:f7a6167b51ac4615a3a8e46fa59da3272021-11-19T05:25:18ZCausal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study2296-861X10.3389/fnut.2021.747547https://doaj.org/article/f7a6167b51ac4615a3a8e46fa59da3272021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnut.2021.747547/fullhttps://doaj.org/toc/2296-861XBackground/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis.Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy.Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13–1.29, p = 3.16 × 10−4), ferritin (OR = 1.32, 95%CI = 1.07–1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06–1.23, p = 5.43 × 10−4) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed.Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy.Yuanlong HuYuanlong HuXiaomeng ChengXiaomeng ChengHuaiyu MaoXianhai ChenXianhai ChenYue CuiZhanjun QiuZhanjun QiuFrontiers Media S.A.articleiron statusiron metabolismsepsisinfectionbidirectional mendelian randomization analysesNutrition. Foods and food supplyTX341-641ENFrontiers in Nutrition, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	iron status iron metabolism sepsis infection bidirectional mendelian randomization analyses Nutrition. Foods and food supply TX341-641
spellingShingle	iron status iron metabolism sepsis infection bidirectional mendelian randomization analyses Nutrition. Foods and food supply TX341-641 Yuanlong Hu Yuanlong Hu Xiaomeng Cheng Xiaomeng Cheng Huaiyu Mao Xianhai Chen Xianhai Chen Yue Cui Zhanjun Qiu Zhanjun Qiu Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study
description	Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis.Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy.Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13–1.29, p = 3.16 × 10−4), ferritin (OR = 1.32, 95%CI = 1.07–1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06–1.23, p = 5.43 × 10−4) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed.Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy.
format	article
author	Yuanlong Hu Yuanlong Hu Xiaomeng Cheng Xiaomeng Cheng Huaiyu Mao Xianhai Chen Xianhai Chen Yue Cui Zhanjun Qiu Zhanjun Qiu
author_facet	Yuanlong Hu Yuanlong Hu Xiaomeng Cheng Xiaomeng Cheng Huaiyu Mao Xianhai Chen Xianhai Chen Yue Cui Zhanjun Qiu Zhanjun Qiu
author_sort	Yuanlong Hu
title	Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study
title_short	Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study
title_full	Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study
title_fullStr	Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study
title_full_unstemmed	Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study
title_sort	causal effects of genetically predicted iron status on sepsis: a two-sample bidirectional mendelian randomization study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f7a6167b51ac4615a3a8e46fa59da327
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Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study

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