Gill, D; Monori, G; Tzoulaki, I; Dehghan, A
(2018)
Iron Status and Risk of Stroke.
Stroke, 49 (12).
pp. 2815-2821.
ISSN 1524-4628
https://doi.org/10.1161/STROKEAHA.118.022701
SGUL Authors: Gill, Dipender Preet Singh
Abstract
Background and Purpose- Both iron deficiency and excess have been associated with stroke risk in observational studies. However, such associations may be attributable to confounding from environmental factors. This study uses the Mendelian randomization technique to overcome these limitations by investigating the association between genetic variants related to iron status and stroke risk. Methods- A study of 48 972 subjects performed by the Genetics of Iron Status consortium identified genetic variants with concordant relations to 4 biomarkers of iron status (serum iron, transferrin saturation, ferritin, and transferrin) that supported their use as instruments for overall iron status. Genetic estimates from the MEGASTROKE consortium were used to investigate the association between the same genetic variants and stroke risk. The 2-sample ratio method Mendelian randomization approach was used for the main analysis, with the MR-Egger and weighted median techniques used in sensitivity analyses. Results- The main results, reported as odds ratio (OR) of stroke per SD unit increase in genetically determined iron status biomarker, showed a detrimental effect of increased iron status on stroke risk (serum iron OR, 1.07; 95% CI, 1.01-1.14; [log-transformed] ferritin OR, 1.18; 95% CI, 1.02-1.36; and transferrin saturation OR, 1.06; 95% CI, 1.01-1.11). A higher transferrin, indicative of lower iron status, was also associated with decreased stroke risk (OR, 0.92; 95% CI, 0.86-0.99). Examining ischemic stroke subtypes, we found the detrimental effect of iron status to be driven by cardioembolic stroke. These results were supported in statistical sensitivity analyses more robust to the inclusion of pleiotropic variants. Conclusions- This study provides Mendelian randomization evidence that higher iron status is associated with increased stroke risk and, in particular, cardioembolic stroke. Further work is required to investigate the underlying mechanism and whether this can be targeted in preventative strategies.
Item Type: |
Article
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Additional Information: |
© 2018 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
Keywords: |
diet, ferritin, iron, stroke, transferrin, Ferritins, Humans, Iron, Mendelian Randomization Analysis, Odds Ratio, Polymorphism, Single Nucleotide, Stroke, Transferrin, Humans, Iron, Transferrin, Odds Ratio, Polymorphism, Single Nucleotide, Ferritins, Stroke, Mendelian Randomization Analysis, 1103 Clinical Sciences, 1102 Cardiorespiratory Medicine and Haematology, 1109 Neurosciences, Neurology & Neurosurgery |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Stroke |
ISSN: |
1524-4628 |
Language: |
eng |
Dates: |
Date | Event |
---|
December 2018 | Published | 25 October 2018 | Published Online | 24 September 2018 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
PubMed ID: |
30571402 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/112810 |
Publisher's version: |
https://doi.org/10.1161/STROKEAHA.118.022701 |
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