Gill, D; Brewer, CF; Monori, G; Trégouët, D-A; Franceschini, N; Giambartolomei, C; INVENT Consortium; Tzoulaki, I; Dehghan, A
(2019)
Effects of Genetically Determined Iron Status on Risk of Venous Thromboembolism and Carotid Atherosclerotic Disease: A Mendelian Randomization Study.
J Am Heart Assoc, 8 (15).
e012994.
ISSN 2047-9980
https://doi.org/10.1161/JAHA.119.012994
SGUL Authors: Gill, Dipender Preet Singh
Abstract
Background Systemic iron status has been implicated in atherosclerosis and thrombosis. The aim of this study was to investigate the effect of genetically determined iron status on carotid intima-media thickness, carotid plaque, and venous thromboembolism using Mendelian randomization. Methods and Results Genetic instrumental variables for iron status were selected from a genome-wide meta-analysis of 48 972 subjects. Genetic association estimates for carotid intima-media thickness and carotid plaque were obtained using data from 71 128 and 48 434 participants, respectively, and estimates for venous thromboembolism were obtained using data from a study incorporating 7507 cases and 52 632 controls. Conventional 2-sample summary data Mendelian randomization was performed for the main analysis. Higher genetically determined iron status was associated with increased risk of venous thromboembolism. Odds ratios per SD increase in biomarker levels were 1.37 (95% CI 1.14-1.66) for serum iron, 1.25 (1.09-1.43) for transferrin saturation, 1.92 (1.28-2.88) for ferritin, and 0.76 (0.63-0.92) for serum transferrin (with higher transferrin levels representing lower iron status). In contrast, higher iron status was associated with lower risk of carotid plaque. Corresponding odds ratios were 0.85 (0.73-0.99) for serum iron and 0.89 (0.80-1.00) for transferrin saturation, with concordant trends for serum transferrin and ferritin that did not reach statistical significance. There was no Mendelian randomization evidence of an effect of iron status on carotid intima-media thickness. Conclusions These findings support previous work to suggest that higher genetically determined iron status is protective against some forms of atherosclerotic disease but increases the risk of thrombosis related to stasis of blood.
Item Type: |
Article
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Additional Information: |
Copyright © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
Keywords: |
Mendelian randomization, atherosclerosis, thrombosis, Biomarkers, Carotid Artery Diseases, Carotid Intima-Media Thickness, Female, Ferritins, Humans, Iron, Male, Mendelian Randomization Analysis, Risk Assessment, Transferrin, Venous Thromboembolism, INVENT Consortium, Humans, Carotid Artery Diseases, Iron, Transferrin, Risk Assessment, Female, Male, Ferritins, Venous Thromboembolism, Mendelian Randomization Analysis, Carotid Intima-Media Thickness, Biomarkers |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
J Am Heart Assoc |
ISSN: |
2047-9980 |
Language: |
eng |
Dates: |
Date | Event |
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6 August 2019 | Published | 16 July 2019 | Published Online | 21 May 2019 | Accepted |
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Publisher License: |
Creative Commons: Attribution-Noncommercial 4.0 |
PubMed ID: |
31310728 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/112804 |
Publisher's version: |
https://doi.org/10.1161/JAHA.119.012994 |
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