Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study
Although observational studies have shown that abnormal systemic iron status is associated with an increased risk of heart failure (HF), it remains unclear whether this relationship represents true causality. We aimed to explore the causal relationship between iron status and HF risk. Two-sample Men...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2072-6643/14/16/3258 |
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| author | Xingchen Wang Xizhi Wang Yingchao Gong Xiaoou Chen Danfeng Zhong Jun Zhu Lenan Zhuang Jing Gao Guosheng Fu Xue Lu Dongwu Lai |
| author_facet | Xingchen Wang Xizhi Wang Yingchao Gong Xiaoou Chen Danfeng Zhong Jun Zhu Lenan Zhuang Jing Gao Guosheng Fu Xue Lu Dongwu Lai |
| author_sort | Xingchen Wang |
| collection | DOAJ |
| description | Although observational studies have shown that abnormal systemic iron status is associated with an increased risk of heart failure (HF), it remains unclear whether this relationship represents true causality. We aimed to explore the causal relationship between iron status and HF risk. Two-sample Mendelian randomisation (MR) was applied to obtain a causal estimate. Genetic summary statistical data for the associations (<i>p</i> < 5 × 10<sup>−8</sup>) between single nucleotide polymorphisms (SNPs) and four iron status parameters were obtained from the Genetics of Iron Status Consortium in genome-wide association studies involving 48,972 subjects. Statistical data on the association of SNPs with HF were extracted from the UK biobank consortium (including 1088 HF cases and 360,106 controls). The results were further tested using MR based on the Bayesian model averaging (MR-BMA) and multivariate MR (MVMR). Of the twelve SNPs considered to be valid instrumental variables, three SNPs (rs1800562, rs855791, and rs1799945) were associated with all four iron biomarkers. Genetically predicted iron status biomarkers were not causally associated with HF risk (all <i>p</i> > 0.05). Sensitivity analysis did not show evidence of potential heterogeneity and horizontal pleiotropy. Convincing evidence to support a causal relationship between iron status and HF risk was not found. The strong relationship between abnormal iron status and HF risk may be explained by an indirect mechanism. |
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| language | English |
| last_indexed | 2024-03-09T12:50:19Z |
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| spelling | doaj.art-c15e7eddf1f343bd82a5dfb6267062d02023-11-30T22:07:33ZengMDPI AGNutrients2072-66432022-08-011416325810.3390/nu14163258Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation StudyXingchen Wang0Xizhi Wang1Yingchao Gong2Xiaoou Chen3Danfeng Zhong4Jun Zhu5Lenan Zhuang6Jing Gao7Guosheng Fu8Xue Lu9Dongwu Lai10Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaAlthough observational studies have shown that abnormal systemic iron status is associated with an increased risk of heart failure (HF), it remains unclear whether this relationship represents true causality. We aimed to explore the causal relationship between iron status and HF risk. Two-sample Mendelian randomisation (MR) was applied to obtain a causal estimate. Genetic summary statistical data for the associations (<i>p</i> < 5 × 10<sup>−8</sup>) between single nucleotide polymorphisms (SNPs) and four iron status parameters were obtained from the Genetics of Iron Status Consortium in genome-wide association studies involving 48,972 subjects. Statistical data on the association of SNPs with HF were extracted from the UK biobank consortium (including 1088 HF cases and 360,106 controls). The results were further tested using MR based on the Bayesian model averaging (MR-BMA) and multivariate MR (MVMR). Of the twelve SNPs considered to be valid instrumental variables, three SNPs (rs1800562, rs855791, and rs1799945) were associated with all four iron biomarkers. Genetically predicted iron status biomarkers were not causally associated with HF risk (all <i>p</i> > 0.05). Sensitivity analysis did not show evidence of potential heterogeneity and horizontal pleiotropy. Convincing evidence to support a causal relationship between iron status and HF risk was not found. The strong relationship between abnormal iron status and HF risk may be explained by an indirect mechanism.https://www.mdpi.com/2072-6643/14/16/3258heart failureiron statusMendelian randomisationcausal association |
| spellingShingle | Xingchen Wang Xizhi Wang Yingchao Gong Xiaoou Chen Danfeng Zhong Jun Zhu Lenan Zhuang Jing Gao Guosheng Fu Xue Lu Dongwu Lai Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study Nutrients heart failure iron status Mendelian randomisation causal association |
| title | Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study |
| title_full | Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study |
| title_fullStr | Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study |
| title_full_unstemmed | Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study |
| title_short | Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study |
| title_sort | appraising the causal association between systemic iron status and heart failure risk a mendelian randomisation study |
| topic | heart failure iron status Mendelian randomisation causal association |
| url | https://www.mdpi.com/2072-6643/14/16/3258 |
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