An observational and Mendelian randomisation study on iron status and sepsis

Fergus Hamilton*, Ruth Mitchell, Haroon Ahmed, Peter Ghazal, Nicholas J. Timpson

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)
27 Downloads (Pure)


Iron deficiency is associated with a substantial burden of morbidity. However, supplementation of iron has been linked to increased rates of serious infection in randomised trials of children in sub-Saharan Africa. Randomised trials in other settings have been inconclusive and it is unknown if changes in levels of iron biomarkers are linked to sepsis in these other settings. We used genetic variants associated with levels of iron biomarkers as instrumental variables in a Mendelian randomisation (MR) analysis to test the hypothesis that increasing levels of iron biomarkers increase the risk of sepsis. In observational and MR analyses we found that increases in iron biomarkers increase the odds of sepsis. In stratified analyses, we show that this risk may be larger in those with iron deficiency and/or anaemia. Taken together, results here suggest a required caution in supplementation of iron and underline the role of iron homeostasis in severe infection.

Original languageEnglish
Article number2867
JournalScientific Reports
Issue number1
Publication statusPublished - Dec 2023

Bibliographical note

Funding Information:
FH’s time was funded by the GW4-CAT Wellcome Doctoral Fellowship Scheme. UK Biobank was funded by the Wellcome Trust, the Medical Research Council, the NIHR, and a variety of other charities ( ). FinnGen is a public–private partnership ( ) funded by multiple instititions across Finland. We want to acknowledge the participants and investigators of the FinnGen study. PG’s time was funded by the Ser Cymru programme, the Welsh Government, and the EU-ERDF. The funder had no role in the design, analysis, or reporting of this study.

Publisher Copyright:
© 2023, The Author(s).


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