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Mendelian randomization study reveals a causal relationship between serum iron status and coronary heart disease and
Fenglan Liu1,2,3, Yanfei Liu1,2, Shihan Xu1,2
1The Second Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Insights
This study used Mendelian randomization to investigate the causal link between iron status and coronary heart disease (CHD). Higher iron levels were associated with a reduced risk of coronary atherosclerosis and myocardial infarction.
Area of Science:
- Cardiovascular Genetics
- Nutritional Biochemistry
- Epidemiology
Background:
- Observational studies suggest a link between systemic iron status and coronary heart disease (CHD), but findings are inconsistent.
- The causal relationship between iron status and CHD, including related cardiovascular diseases (CVD), requires further investigation.
Purpose of the Study:
- To examine the potential causal relationship between serum iron status and CHD and related CVD.
- Utilized a two-sample Mendelian randomization (MR) approach to assess causality.
Main Methods:
- Employed genetic statistics from large-scale genome-wide association studies (GWAS) for four iron status parameters.
- Selected three single nucleotide polymorphisms (SNPs) as instrumental variables for iron biomarkers.
- Applied five MR methods (IVW, MR Egger, weighted median, weighted mode, Wald ratio) to analyze summary-level GWAS data for CHD and related CVD.
Main Results:
- Serum iron showed a negative association with the odds of coronary atherosclerosis (OR=0.995, P=0.002).
- Transferrin saturation (TS) was negatively associated with the odds of myocardial infarction (MI) (OR=0.885, P=0.02).
Conclusions:
- The MR analysis supports a causal relationship between whole-body iron status and CHD development.
- Findings suggest that a higher iron status may correlate with a decreased risk of developing CHD.
Background:
Growing observational studies have shown that abnormal systemic iron status is associated with Coronary heart disease (CHD). However, these results from observational studies was not entirely consistent.It remains unclear whether this relationship represents causality.It is necessary to explore the causal relationship between iron status and CHD and related cardiovascular diseases (CVD).
Objective:
We aimed to investigate the potential casual relationship between serum iron status and CHD and related CVD using a two-sample Mendelian randomization (MR) approach.
Methods:
Genetic statistics for single nucleotide polymorphisms (SNPs) between four iron status parameters were identified in a large-scale genome-wide association study (GWAS) conducted by the Iron Status Genetics organization. Three independent single nucleotide polymorphisms (SNPs) (rs1800562, rs1799945, and rs855791) aligned with four iron status biomarkers were used as instrumental variables. CHD and related CVD genetic statistics We used publicly available summary-level GWAS data. Five different MR methods random effects inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and Wald ratio were used to explore the causal relationship between serum iron status and CHD and related CVD.
Results:
In the MR analysis, we found that the causal effect of serum iron (OR = 0.995, 95% CI = 0.992-0.998, p = 0.002) was negatively associated with the odds of coronary atherosclerosis (AS). Transferrin saturation (TS) (OR = 0.885, 95% CI = 0.797-0.982, p = 0.02) was negatively associated with the odds of Myocardial infarction (MI).
Conclusion:
This MR analysis provides evidence for a causal relationship between whole-body iron status and CHD development. Our study suggests that a high iron status may be associated with a reduced risk of developing CHD.
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