Using Mendelian randomization to determine whether iron status is causally related to the risks of severe malaria and invasive bacterial infections in African children

Iron deficiency is common and iron supplementation improves developmental outcomes in African children. Despite these benefits, it is uncertain whether improving iron status might increase the risks of malaria and invasive bacterial infections. Observational studies indicate that higher ferritin concentrations increase the risk of malaria, but it is unclear whether higher ferritin levels are a cause or a consequence of infection. Alternately, randomized controlled trials of iron supplementation have reported inconsistent effects and few trials have been sufficiently powered to assess the risks of severe malaria or bacteraemia. This project’s approach requires two steps. The first step is to identify common genetic variants that alter iron status by conducting a genome-wide association study in 4870 children in 5 African countries. The second step is to assess whether inherited variation in iron status influences the risk of severe infection within large case- control studies of 7,589 severe malaria cases and 2,530 bacteraemia cases with similar numbers of controls. This project is achievable through collaboration. The findings of the project will be used to inform public health policy.

Basic Science
Genetics and Genomics

Sep 2016 — Mar 2022

$712,170

United Kingdom