Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis
Background and aimsAlthough iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2022.964163/full |
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| author | Kai Wang Kai Wang Kai Wang Fangkun Yang Pengcheng Zhang Yang Yang Li Jiang |
| author_facet | Kai Wang Kai Wang Kai Wang Fangkun Yang Pengcheng Zhang Yang Yang Li Jiang |
| author_sort | Kai Wang |
| collection | DOAJ |
| description | Background and aimsAlthough iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of liver injury and various liver diseases. Moreover, in light of the sex-dependent iron regulation in human beings, we further estimated the sex-specific effect of iron levels in liver diseases.MethodsIndependent single nucleotide polymorphisms associated with systemic iron status (including four indicators) at the genome-wide significance level from the Genetics of Iron Status (GIS) Consortium were selected as instrumental variables. Summary data for six liver function biomarkers and five liver diseases were obtained from the UK Biobank, the Estonian Biobank, the eMERGE network, and FinnGen consortium. Mendelian Randomization assessment of the effect of iron on liver function and liver diseases was conducted.ResultsGenetically predicted iron levels were positively and significantly associated with an increased risk of different dimensions of liver injury. Furthermore, increased iron status posed hazardous effects on non-alcoholic fatty liver disease, alcoholic liver disease, and liver fibrosis/cirrhosis. Sex-stratified analyses indicated that the hepatoxic role of iron might exist in NAFLD and liver fibrosis/cirrhosis development among men. No significantly causal relationship was found between iron status and viral hepatitis.ConclusionOur study adds to current knowledge on the genetic role of iron in the risk of liver injury and related liver diseases, which provides clinical and public health implications for liver disease prevention as iron status can be modified. |
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| issn | 2296-861X |
| language | English |
| last_indexed | 2024-04-11T09:57:11Z |
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| series | Frontiers in Nutrition |
| spelling | doaj.art-5d54458b191b405bb432323a034fa3fb2022-12-22T04:30:32ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-09-01910.3389/fnut.2022.964163964163Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysisKai Wang0Kai Wang1Kai Wang2Fangkun Yang3Pengcheng Zhang4Yang Yang5Li Jiang6Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaEye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaZhejiang Provincial Key Lab of Ophthalmology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Cardiology, Ningbo First Hospital, School of Medicine, Zhejiang University, Ningbo, ChinaDepartment of Gastroenterology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, ChinaBackground and aimsAlthough iron homeostasis has been associated with liver function in many observational studies, the causality in this relationship remains unclear. By using Mendelian Randomization analyses, we aimed to evaluate the genetic effects of increased systemic iron levels on the risk of liver injury and various liver diseases. Moreover, in light of the sex-dependent iron regulation in human beings, we further estimated the sex-specific effect of iron levels in liver diseases.MethodsIndependent single nucleotide polymorphisms associated with systemic iron status (including four indicators) at the genome-wide significance level from the Genetics of Iron Status (GIS) Consortium were selected as instrumental variables. Summary data for six liver function biomarkers and five liver diseases were obtained from the UK Biobank, the Estonian Biobank, the eMERGE network, and FinnGen consortium. Mendelian Randomization assessment of the effect of iron on liver function and liver diseases was conducted.ResultsGenetically predicted iron levels were positively and significantly associated with an increased risk of different dimensions of liver injury. Furthermore, increased iron status posed hazardous effects on non-alcoholic fatty liver disease, alcoholic liver disease, and liver fibrosis/cirrhosis. Sex-stratified analyses indicated that the hepatoxic role of iron might exist in NAFLD and liver fibrosis/cirrhosis development among men. No significantly causal relationship was found between iron status and viral hepatitis.ConclusionOur study adds to current knowledge on the genetic role of iron in the risk of liver injury and related liver diseases, which provides clinical and public health implications for liver disease prevention as iron status can be modified.https://www.frontiersin.org/articles/10.3389/fnut.2022.964163/fullironmendelian randomizationliver injurynon-alcoholic fatty liver diseaseliver fibrosis/ cirrhosis |
| spellingShingle | Kai Wang Kai Wang Kai Wang Fangkun Yang Pengcheng Zhang Yang Yang Li Jiang Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis Frontiers in Nutrition iron mendelian randomization liver injury non-alcoholic fatty liver disease liver fibrosis/ cirrhosis |
| title | Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis |
| title_full | Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis |
| title_fullStr | Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis |
| title_full_unstemmed | Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis |
| title_short | Genetic effects of iron levels on liver injury and risk of liver diseases: A two-sample Mendelian randomization analysis |
| title_sort | genetic effects of iron levels on liver injury and risk of liver diseases a two sample mendelian randomization analysis |
| topic | iron mendelian randomization liver injury non-alcoholic fatty liver disease liver fibrosis/ cirrhosis |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2022.964163/full |
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