A Mendelian Randomization Study on the Effect of Iron Status on Myocardial Infarction

Abstract

Background: Observational studies have suggested associations between iron status and myocardial infarction (MI). However, it’s role as a risk factor or as a subeffect because of myocardial infarction is uncertain. Methods: We performed a literature search of genome-wide studies that evaluate iron status. We used a two-sample Mendelian randomization approach to evaluate the causality of iron status on myocardial infarction risk, using 2 cohorts: GIS (n=23,986) and UK Biobank(n=361,194). The two-sample MR study was conducted to estimate causal relationship between iron status and MI, with the inverse-variance weighted (IVW)method, weighted-median method. Moreover, MR-Egger regression, MR-PRESSO and leave-one-out analysis were performed to evaluate the potential pleiotropy effect. Results: Genome-wide association studies of iron status were evaluated. No associations were found in relation to myocardial infarction: iron [odds ratio(OR)=1.03[95% confidence interval CI,0.79-1.35];p-value=8.09×10−1], ferritin(OR=0.99[95% CI, 0.99-1.00];p-value=3.62×10−1), transferrin(OR =0.99[95% CI, 0.99-1.00];p-value=5.98×10−1), transferrin saturation(OR =0.99[95% CI, 0.99-1.00];p-value=4.55×10−1). MR-Egger, MR-PRESSO, and leave-one-out analysis did not indicate horizontal pleiotropy. Conclusion: Our MR study suggested that genetically predicted iron status was not causally associated with MI among the European populations.