Kemri-Wellcome Trust Research Programme: Using Mendelian randomisation to determine whether iron status is causally linked to severe infections and death in African children

Despite high prevalence of iron deficiency and anaemia in Africa, there are longstanding concerns regarding whether treatment of iron deficiency by giving iron supplements increases the risk of infections, hospitalisation, and deaths. Previous studies have not conclusively addressed this dilemma due to study design limitations such as confounding bias, reverse causality and a requirement of large sample sizes and long follow-up times to investigate rare outcomes in clinical trials. During my post-doctoral studies, I conducted a GWAS and identified novel genetic variants that are unique to African populations that can be used to proxy iron status and anaemia. This now affords me the unique and exciting opportunity to test how these variants influence severe infections and mortality using a Mendelian randomisation approach that overcomes many of the limitations of previous study designs. I propose to identify likely causal genetic variants through fine-mapping, comprehensive functional annotation, and integration of my findings with transcriptomic and epigenomic data. I will then determine whether the prioritised causal variants influence risk of severe malaria, bacteraemia, tuberculosis, and mortality using already available data/samples from large case-control studies in Africa. This novel approach has not previously been applied to iron status and infections/deaths in Africa.

Programme: International Training Fellowship

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