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The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study

Gill, D; Del Greco M, F; Walker, AP; Srai, SKS; Laffan, MA; Minelli, C; (2017) The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study. Arteriosclerosis, Thrombosis, and Vascular Biology , 37 pp. 1788-1792. 10.1161/ATVBAHA.117.309757. Green open access

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Abstract

OBJECTIVE: Iron status is a modifiable trait that has been implicated in cardiovascular disease. This study uses the Mendelian randomization technique to investigate whether there is any causal effect of iron status on risk of coronary artery disease (CAD). APPROACH AND RESULTS: A 2-sample Mendelian randomization approach is used to estimate the effect of iron status on CAD risk. Three loci (rs1800562 and rs1799945 in the HFE gene and rs855791 in TMPRSS6) that are each associated with serum iron, transferrin saturation, ferritin, and transferrin in a pattern suggestive of an association with systemic iron status are used as instruments. single-nucleotide polymorphism-iron status association estimates are based on a genome-wide association study meta-analysis of 48 972 individuals. single-nucleotide polymorphism-CAD estimates are derived by combining the results of a genome-wide association study meta-analysis of 60 801 CAD cases and 123 504 controls with those of a meta-analysis of 63 746 CAD cases and 130 681 controls obtained from Metabochip and genome-wide association study studies. Combined Mendelian randomization estimates are obtained for each marker by pooling results across the 3 instruments. We find evidence of a protective effect of higher iron status on CAD risk (iron odds ratio, 0.94 per SD unit increase; 95% confidence interval, 0.88-1.00; P=0.039; transferrin saturation odds ratio, 0.95 per SD unit increase; 95% confidence interval, 0.91-0.99; P=0.027; log-transformed ferritin odds ratio, 0.85 per SD unit increase; 95% confidence interval, 0.73-0.98; P=0.024; and transferrin odds ratio, 1.08 per SD unit increase; 95% confidence interval, 1.01-1.16; P=0.034). CONCLUSIONS: This Mendelian randomization study supports the hypothesis that higher iron status reduces CAD risk. These findings may highlight a therapeutic target.

Type: Article
Title: The Effect of Iron Status on Risk of Coronary Artery Disease: A Mendelian Randomization Study
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/ATVBAHA.117.309757
Publisher version: http://dx.doi.org/10.1161/ATVBAHA.117.309757
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: biomarkers, cardiovascular diseases, coronary artery disease, iron, risk
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1560335
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